Regularly updated systematic evidence

STUDIES ON MONONUCLEAR CELLS OBTAINED FROM SYNOVIAL FLUID OF PATIENTS WITH DIFFERENT TYPES OF ARTHRITIS. CYTOTOXIC EFFECT ON TISSUE-CULTURED HUMAN FIBROBLASTS.

I apologize, but I cannot provide a meaningful summary of this study as the abstract is listed as "NA" (not available).

To write an accurate summary focusing on the study objective, methods, findings regarding phenotypes/subgroups, and implications for osteoarthritis management or physiotherapy, I would need access to the actual abstract content or the full paper.

If you could provide the abstract text, I would be happy to create a concise 3-4 sentence summary in plain language addressing the specific aspects you've requested.

PATHOGENETIC TYPES OF COXARTHROSIS AND IMPLICATIONS FOR TREATMENT.

This study aimed to classify different types of hip osteoarthritis (coxarthrosis) based on their underlying causes to guide treatment decisions. The researchers examined 150 patients and categorized their hip arthritis according to whether anatomical defects or primary cartilage disorders were present, and assessed the bone's ability to repair and remodel itself.

The study identified two main phenotypes: "hypertrophic OA" occurring in hips with anatomical abnormalities that showed strong bone repair responses, and "atrophic OA" in hips with previous inflammatory disease that showed minimal bone repair. The researchers found that hip arthritis behavior depends on three interacting factors: cartilage breakdown, excessive mechanical stress, and the bone's repair response.

For treatment implications, patients with the hypertrophic type (anatomical problems with good bone repair) had better outcomes with corrective surgeries like osteotomy and more secure prosthetic implant fixation, while those with the atrophic type (inflammatory/degenerative features with poor bone repair) progressed faster and responded poorly to osteotomy procedures.

ALTERED EXPRESSION OF COLLAGEN PHENOTYPE IN OSTEOARTHROSIS.

This study aimed to identify and characterize different types of collagen present in osteoarthritic cartilage to better understand the disease's molecular changes. The researchers used immunofluorescence microscopy to visualize collagen types and employed sophisticated biochemical techniques including enzyme digestion, ion-exchange chromatography, and amino acid analysis to isolate and identify specific collagen molecules from osteoarthritic cartilage samples.

The key finding was that osteoarthritic cartilage contains an abnormal collagen phenotype, specifically the presence of type III collagen alongside the normally expected types I and II, plus increased fibronectin protein compared to healthy cartilage. This altered collagen composition represents a distinct molecular subgroup or phenotype of osteoarthritis characterized by abnormal tissue remodeling and repair processes.

These findings suggest that osteoarthritis involves complex changes in cartilage composition that could potentially be targeted for treatment, and may help explain why patients respond differently to physiotherapy interventions depending on their underlying cartilage biochemistry.

DECREASED TISSUE IMMUNOREGULATORY INDEX IN RHEUMATOID SYNOVITIS, DETERMINED BY IN-SITU T-CELL PHENOTYPING WITH MONOCLONAL ANTIBODIES.

I apologize, but I cannot provide a meaningful summary of this research study because the abstract is listed as "NA" (not available).

However, I can note that based on the title alone, this appears to be a study about rheumatoid arthritis rather than osteoarthritis, focusing on immune cell analysis in joint tissue using specialized antibody techniques.

To provide the comprehensive 3-4 sentence summary you've requested covering study objectives, methods, phenotyping findings, and physiotherapy implications, I would need access to the full abstract or study details. Could you please provide the complete abstract text?

ANTIBODIES TO CANINE COLLAGEN TYPES I AND II IN DOGS WITH SPONTANEOUS CRUCIATE LIGAMENT RUPTURE AND OSTEOARTHRITIS.

This study investigated whether dogs with cruciate ligament rupture and knee osteoarthritis develop immune responses against their own joint tissues. Researchers used blood and joint fluid samples from 30 affected dogs and 15 healthy controls, testing for antibodies against two types of collagen (structural proteins in ligaments and cartilage) using laboratory immune assays. The findings revealed that most dogs with joint disease had developed antibodies against their own collagen - over half showed immune reactions in blood samples, while nearly 90% had antibodies present directly in the affected joint fluid, suggesting the immune system was attacking damaged ligament and cartilage tissue. These results indicate that osteoarthritis following ligament injury may involve an autoimmune component, which could inform future treatment approaches by suggesting that therapies targeting immune responses might be beneficial alongside traditional rehabilitation methods.

ANTIBODIES TO TYPES I, II, IX, AND XI COLLAGEN IN THE SERUM OF PATIENTS WITH RHEUMATIC DISEASES.

This study aimed to identify different patterns of immune responses in patients with various rheumatic diseases by measuring antibodies against four types of collagen in their blood. The researchers used a specialized blood test to detect antibodies to collagen types I, II, IX, and XI in 104 patients with rheumatoid arthritis, osteoporosis, Paget's disease, or osteoarthritis. They found distinct antibody patterns across disease groups: type XI collagen antibodies were most common (found in about 50% of patients with rheumatoid arthritis, Paget's disease, and osteoporosis), while type IX collagen antibodies were specifically elevated only in rheumatoid arthritis patients (44%). Importantly, patients with these collagen antibodies appeared to have milder or earlier-stage disease, suggesting these immune markers might help identify patient subgroups who could benefit from earlier, less aggressive treatment approaches in physiotherapy and rehabilitation.

OSTEOARTHRITIS AND BONE: OSTEOLOGIC TYPES OF OSTEOARTHRITIS OF THE HIP.

This study aimed to classify different bone types in hip osteoarthritis to better understand disease progression and treatment options. Researchers examined 93 femoral heads from patients with primary hip osteoarthritis using detailed bone analysis (histomorphometry) and identified three distinct bone patterns. They found three main subgroups: osteosclerotic type (77% of cases) with typical bone changes, hyperostotic type (10%) characterized by excessive bone growth and large bone spurs, and osteopenic type (8%) showing bone loss, more cysts, and smaller bone spurs. These findings suggest that hip osteoarthritis patients have different underlying bone disease patterns, which could help physiotherapists and clinicians tailor treatment approaches and better predict which patients might benefit from different interventions like joint replacement or bone grafting procedures.

HLA-A, B ANTIGENS AND ALPHA 1-ANTITRYPSIN PHENOTYPES IN NODAL GENERALISED OSTEOARTHRITIS AND EROSIVE OSTEOARTHRITIS.

This study aimed to identify genetic markers associated with different forms of hand osteoarthritis by examining HLA antigens and alpha 1-antitrypsin phenotypes in 90 patients with nodal generalized osteoarthritis. Researchers compared the frequency of specific genetic markers between patients and reference populations, and analyzed radiographic severity scores. The study identified two distinct osteoarthritis subgroups: patients with nodal generalized osteoarthritis showed increased frequency of HLA-A1B8 and MZ alpha 1-antitrypsin phenotypes, while a subset with erosive osteoarthritis (characterized by bone erosions) had higher frequency of the MS alpha 1-antitrypsin phenotype and more severe radiographic changes. These findings suggest that genetic profiling could help identify different osteoarthritis phenotypes with varying inflammatory components, potentially allowing physiotherapists and clinicians to tailor management approaches based on the underlying disease subtype and expected progression patterns.

SECRETION OF ANTIBODIES TO TYPES I AND II COLLAGEN BY SYNOVIAL TISSUE CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS.

This study aimed to investigate whether immune cells in the joint tissue of rheumatoid arthritis (RA) patients produce antibodies against collagen, the main structural protein in cartilage and bone. Researchers used a specialized laboratory technique to detect antibody-producing cells in synovial tissue samples from RA patients and compared them to patients with other joint diseases.

The key finding was that most RA patients (21 out of 27) had immune cells in their joints actively producing antibodies against type II collagen (the main cartilage component), regardless of whether they tested positive for rheumatoid factor in blood tests. Importantly, these collagen-attacking antibodies were not detectable in the patients' blood samples, and patients with other joint conditions did not show this local immune response.

This research reveals that RA patients can be grouped into those with and without local autoimmune attacks on cartilage collagen, which occurs directly within the joint rather than systemically. For physiotherapy and rehabilitation, this suggests that joint-specific inflammatory processes may be more important than blood markers for understanding disease activity, and that cartilage protection strategies may be particularly crucial in RA management since the immune system is actively targeting the cartilage structure.

IMMUNOCYTOCHEMICAL ANALYSIS OF HUMAN SYNOVIAL LINING CELLS: PHENOTYPIC RELATION TO OTHER MARROW DERIVED CELLS.

This study aimed to characterize the cellular identity of synovial lining cells by comparing their surface markers to those of macrophages and other immune cells. The researchers used immunocytochemical staining with multiple monoclonal antibodies to analyze synovial tissue samples from both normal and diseased (hyperplastic) joints.

The key finding was that synovial lining cells expressed many of the same surface markers as macrophages (including CD68, CD14, and various receptors), suggesting they belong to the same family of immune cells derived from bone marrow. However, synovial lining cells had a distinct marker profile compared to subintimal macrophages, indicating they represent a specialized subgroup of macrophage-like cells.

This research helps establish that synovial lining cells are part of the immune system's mononuclear phagocyte network, which has important implications for understanding joint inflammation in conditions like osteoarthritis and rheumatoid arthritis, potentially informing targeted therapeutic approaches.

TYPES II, VI AND IX COLLAGENS IN NORMAL AND OSTEOARTHROTIC HUMAN ARTICULAR CARTILAGE.

I apologize, but I cannot provide a meaningful summary of this research paper because the abstract is not available (marked as "NA").

To write an accurate summary focusing on the study objective, methods, findings about osteoarthritis phenotypes/subgroups, and implications for physiotherapy management, I would need access to the abstract or additional details about the study's content.

If you could provide the abstract or key details from the paper, I would be happy to create a concise 3-4 sentence summary in plain language addressing the points you've specified.

EVIDENCE FOR THE PRESENCE OF ACTIVATED CD4 T CELLS WITH NAIVE PHENOTYPE IN THE PERIPHERAL BLOOD OF PATIENTS WITH RHEUMATOID ARTHRITIS.

This study investigated whether specific T cell subpopulations are preferentially activated in rheumatoid arthritis (RA) patients compared to other joint conditions. Researchers analyzed blood samples from RA patients, comparing T cell activation markers (CD25 and interferon-gamma) with patients having reactive arthritis, degenerative joint disease, and healthy controls. The key finding was that RA patients uniquely showed activation of naive CD4 T cells (CD45RO-) in their blood, whereas this activation pattern was not seen in other arthritis types or healthy individuals. This discovery suggests RA has a distinct immune signature involving naive T cell activation, which could help differentiate RA from other joint conditions and potentially guide more targeted immunomodulatory treatments, though direct physiotherapy implications are limited given the immunological focus.

AMPLIFICATION OF CDNAS FOR HUMAN CARTILAGE-SPECIFIC TYPES II, IX AND XI COLLAGENS FROM CHONDROCYTES AND EPSTEIN-BARR VIRUS-TRANSFORMED LYMPHOCYTES.

This study aimed to develop better methods for detecting genetic mutations in cartilage-specific collagen genes that cause inherited forms of osteoarthritis and other cartilage diseases. The researchers used RNA polymerase chain reaction (PCR) to amplify genetic material (cDNAs) for three important cartilage collagens (types II, IX, and XI) from very small amounts of cartilage cells and even from transformed blood cells. They successfully amplified the complete genetic sequences for these collagens from as little as 6 nanograms of RNA, and importantly, could detect these genes even in non-cartilage cells. This technical breakthrough allows clinicians to identify genetic mutations causing inherited osteoarthritis using much smaller tissue samples or even blood samples, making genetic testing more accessible and potentially leading to earlier diagnosis and personalized treatment approaches for patients with hereditary cartilage disorders.

EARLY-ONSET OSTEOARTHRITIS LINKED TO THE TYPE II PROCOLLAGEN GENE. DETAILED CLINICAL PHENOTYPE AND FURTHER ANALYSES OF THE GENE.

This study aimed to characterize the clinical features of osteoarthritis in two Finnish families with genetic linkage to the type II collagen gene (COL2A1) and to search for specific mutations in this gene. The researchers used advanced genetic analysis techniques to examine the gene sequences and confirmed strong genetic linkage through statistical analysis. The key finding was that affected family members showed typical osteoarthritis symptoms and joint changes but developed them at an unusually early age, representing a distinct early-onset phenotype without other skeletal abnormalities. These results suggest that early-onset familial osteoarthritis may require different management approaches, and physiotherapists should be aware that some patients may have genetic predispositions leading to earlier joint degeneration than typically expected.

AN INBRED LINE OF TRANSGENIC MICE EXPRESSING AN INTERNALLY DELETED GENE FOR TYPE II PROCOLLAGEN (COL2A1). YOUNG MICE HAVE A VARIABLE PHENOTYPE OF A CHONDRODYSPLASIA AND OLDER MICE HAVE OSTEOARTHRITIC CHANGES IN JOINTS.

This study aimed to investigate how a genetic defect in type II collagen (COL2A1 gene) affects joint development and aging in transgenic mice over their lifespan. Researchers examined mice from 1 day to 15 months old using microscopic analysis, physical measurements, and bone strength testing to track changes in cartilage, bone, and joint health. The findings revealed distinct age-related phenotypes: young mice showed variable severity of chondrodysplasia (cartilage development disorder) with about 15% having severe, life-threatening forms, while surviving mice had subtler cartilage abnormalities and growth problems that actually improved with age. Most importantly, older mice (15 months) developed osteoarthritis-like joint degeneration, suggesting this genetic model demonstrates how early cartilage defects can lead to later joint disease. These findings support the concept that osteoarthritis may have developmental origins and suggest that early intervention strategies in physiotherapy and joint protection might be crucial for individuals with cartilage development issues to prevent later degenerative joint disease.

GENERALIZED OSTEOARTHRITIS ASSOCIATED WITH INCREASED INSULIN-LIKE GROWTH FACTOR TYPES I AND II AND TRANSFORMING GROWTH FACTOR BETA IN CORTICAL BONE FROM THE ILIAC CREST. POSSIBLE MECHANISM OF INCREASED BONE DENSITY AND PROTECTION AGAINST OSTEOPOROSIS.

This study investigated why people with generalized osteoarthritis (affecting multiple joints, particularly hands) tend to have higher bone density and better protection against osteoporosis. Researchers measured growth factors (IGF-I, IGF-II, and TGF-beta) in bone samples from the hip area, comparing people with and without hand osteoarthritis at autopsy. They found significantly higher levels of all three growth factors in the bone of people with osteoarthritis, suggesting these individuals have more active bone-building cells (osteoblasts) throughout their skeleton. This identifies a distinct osteoarthritis phenotype characterized by generalized joint disease combined with systemic increased bone formation, which may require different management approaches that consider both joint and bone health together.

THE INDUCIBLE PRODUCTION OF NITRIC OXIDE BY ARTICULAR CELL TYPES.

This study aimed to identify which joint cells produce nitric oxide (NO) in response to inflammatory signals that may contribute to arthritis-related tissue damage. The researchers tested different joint cell types (cartilage cells and synovial tissue cells) in laboratory cultures, exposing them to inflammatory proteins like interleukin-1 and measuring NO production. The key finding was that cartilage cells (chondrocytes) from both healthy and osteoarthritic patients produced large amounts of NO when stimulated by inflammatory signals, while synovial fibroblasts did not. This research suggests that cartilage cells themselves may contribute to joint tissue breakdown in osteoarthritis through NO production, potentially identifying them as important therapeutic targets for treatments aimed at protecting cartilage or modulating inflammatory responses in rehabilitation approaches.

INCREASED PROTEOGLYCAN SYNTHESIS IN CARTILAGE IN EXPERIMENTAL CANINE OSTEOARTHRITIS DOES NOT REFLECT A PERMANENT CHANGE IN CHONDROCYTE PHENOTYPE.

This study aimed to determine whether the increased cartilage repair activity seen in early osteoarthritis represents a permanent change in cartilage cells or a temporary response to joint damage. The researchers used a dog model where osteoarthritis was induced by cutting knee ligaments, then studied how cartilage cells behaved when removed from the joint and grown in laboratory cultures for up to 3 days.

The key finding was that cartilage from osteoarthritic joints initially showed higher repair activity and different responses to inflammatory signals compared to healthy cartilage, but these differences disappeared within 2-3 days of laboratory culture. This suggests that the enhanced cartilage cell activity in early osteoarthritis is a reversible response to the joint environment rather than a permanent change in cell behavior.

For physiotherapy and management, this indicates that the joint environment plays a crucial role in driving cartilage breakdown and repair processes, suggesting that interventions targeting joint mechanics, loading patterns, and inflammatory factors may be particularly important in early osteoarthritis treatment.

ANALYSIS OF CELL TYPES AND MEDIATOR PRODUCTION FROM TISSUES AROUND LOOSENING JOINT IMPLANTS.

This study aimed to characterize the immune cell types and inflammatory mediators present in tissues surrounding loose joint implants to understand the biological processes involved in implant failure. Researchers used immunophenotypic analysis to examine pseudosynovial membrane (PSM) tissues from patients with aseptically loose implants, measuring cell populations and inflammatory molecule production. The findings revealed significant variation between patients in immune cell composition, with macrophages being the dominant cell type but T-cells comprising over 20% in some cases, and inflammatory patterns similar to those seen in osteoarthritis and rheumatoid arthritis. These results suggest that patients with loose implants may have distinct inflammatory phenotypes, which could inform personalized approaches to managing implant complications and guide rehabilitation strategies based on individual inflammatory profiles.

PHENOTYPIC MODULATION OF NEWLY SYNTHESIZED PROTEOGLYCANS IN HUMAN CARTILAGE AND CHONDROCYTES.

This study aimed to compare the types of proteoglycans (key cartilage building blocks) produced by cells from osteoarthritic versus healthy human cartilage. The researchers used laboratory cultures of cartilage tissue samples and isolated cartilage cells (chondrocytes) from osteoarthritic femoral heads and age-matched healthy cartilage, then analyzed the proteoglycans produced using biochemical techniques.

The key finding was that cells from osteoarthritic cartilage showed a different "phenotype" or cellular behavior pattern - they primarily produced only one type of large proteoglycan (aggrecan), while cells from healthy cartilage produced this same proteoglycan plus two additional types. This difference in proteoglycan production patterns persisted even when the cells were grown in laboratory conditions, suggesting the osteoarthritic cells had undergone lasting changes in their function.

These findings suggest that osteoarthritis involves fundamental changes in how cartilage cells manufacture the building blocks needed for healthy cartilage, which could help explain why damaged cartilage struggles to repair itself and may inform future strategies for cartilage regeneration therapies.

LOOSENING OF THREADED ACETABULAR CUPS IN ARTHROPLASTY OF THE HIP. THE ASSOCIATION WITH DIFFERENT TYPES OF COXARTHROSIS.

This study investigated whether different types of pre-existing hip osteoarthritis (coxarthrosis) affect the success of threaded acetabular cups in hip replacement surgery. The researchers followed 62 patients for an average of 69 months after surgery and classified their original osteoarthritis as atrophic (bone loss), normotrophic (normal bone), or hypertrophic (bone overgrowth). They found that cup loosening occurred significantly more often in patients who originally had atrophic osteoarthritis (5 cases) compared to hypertrophic cases (0 cases), with atrophic cases also showing more radiolucent lines around the implant (61% vs 25%). These findings suggest that osteoarthritis phenotype - particularly whether patients have bone loss or bone growth patterns - should be considered when selecting implant types, as patients with atrophic bone changes may need alternative surgical approaches or closer monitoring after hip replacement.

PCR ASSAY CONFIRMS DIAGNOSIS IN SYNDROME WITH VARIABLY EXPRESSED PHENOTYPE: MUTATION DETECTION IN STICKLER SYNDROME.

**Study Summary:**

This study aimed to develop a genetic test for diagnosing Stickler syndrome, a hereditary condition that causes variable symptoms including severe myopia, hearing loss, cleft palate, and early-onset osteoarthritis. The researchers used a PCR-based genetic assay to detect a specific mutation in the COL2A1 gene (which produces type II collagen) in a three-generation family. They successfully confirmed the diagnosis in a newborn who had atypical symptoms (Pierre-Robin sequence with minimal eye problems), demonstrating how the same genetic mutation can produce very different clinical presentations within one family. The findings suggest that genetic testing could improve diagnosis and management of Stickler syndrome patients, particularly for the musculoskeletal complications like premature osteoarthritis, by enabling earlier identification and preventive treatment regardless of which specific symptoms are most prominent.

ONCOPROTEIN EXPRESSION IN HUMAN SYNOVIAL TISSUE: AN IMMUNOHISTOCHEMICAL STUDY OF DIFFERENT TYPES OF ARTHRITIS.

This study aimed to investigate whether different types of arthritis could be distinguished by examining the expression of specific oncoproteins (proteins involved in cell growth) in joint tissue samples. Researchers used immunohistochemical staining to analyze synovial tissue from 58 patients across six arthritis types, including osteoarthritis, rheumatoid arthritis, and various infectious arthritis conditions.

The findings revealed distinct patterns that grouped the arthritis types into three main phenotypes: osteoarthritis and rheumatoid arthritis each showed unique oncoprotein expression patterns, while reactive/seronegative arthritis formed one group and bacterial arthritis conditions formed another. Most oncoproteins (MYC, MYB, FOS, JUN) correlated with the degree of inflammation and immune cell infiltration in the joint tissue, but RAS protein did not show this relationship.

These results suggest that oncoprotein expression patterns reflect the inflammatory response rather than disease-specific abnormalities, indicating that arthritis phenotyping based on molecular markers may help distinguish between inflammatory and degenerative joint conditions. For physiotherapy practice, this supports the importance of tailoring rehabilitation approaches based on the underlying arthritis type, as the distinct molecular profiles likely correspond to different tissue responses and healing processes.

COMPARISON OF RESULTS OF DIFFERENT TYPES OF KNEE ARTHROPLASTIES.

This study aimed to compare outcomes of different knee replacement types by analyzing 18 years of surgical experience at a Hungarian orthopedic center. The researchers reviewed 1,103 knee arthroplasties performed between 1976-1994, comparing three prosthesis types: constrained (hinge), unconstrained (sledge), and semiconstrained (total condylar) implants in patients with osteoarthritis (50.9%), rheumatoid arthritis (40.7%), and other conditions.

The study found distinct complication patterns between patient subgroups and implant types: constrained prostheses had the highest complication rate (17.8%, mostly within the first year), unconstrained prostheses showed lower complications (5.3%, typically after one year), while semiconstrained prostheses demonstrated the best outcomes with knee function scores improving from 38% to over 80%.

These findings suggest that patient phenotyping based on underlying diagnosis and joint stability requirements is crucial for selecting appropriate implant types, with semiconstrained total condylar prostheses showing superior functional outcomes and potentially requiring less intensive post-operative physiotherapy protocols due to their lower complication rates.

MUTATIONS IN FIBRILLAR COLLAGENS (TYPES I, II, III, AND XI), FIBRIL-ASSOCIATED COLLAGEN (TYPE IX), AND NETWORK-FORMING COLLAGEN (TYPE X) CAUSE A SPECTRUM OF DISEASES OF BONE, CARTILAGE, AND BLOOD VESSELS.

This study aimed to catalog and analyze genetic mutations in six different types of collagen genes and their associated diseases by examining 278 mutations from 317 unrelated patients. The researchers used genetic analysis to identify mutation types and patterns, finding that 78% were single-base mutations that either changed critical amino acids (63%) or affected RNA splicing (13%), with most amino acid changes involving substitutions for glycine in the collagen structure. The mutations created distinct disease phenotypes/subgroups including osteogenesis imperfecta, various bone and cartilage disorders (chondrodysplasias), Ehlers-Danlos syndrome, and some forms of osteoporosis, osteoarthritis, and blood vessel problems. These findings suggest that genetic testing could help identify specific collagen-related subtypes of musculoskeletal conditions, potentially allowing physiotherapists and clinicians to tailor rehabilitation approaches based on the underlying collagen defect and associated tissue fragility or structural abnormalities.

PHENOTYPIC MODULATION OF CHONDROCYTES AS A POTENTIAL THERAPEUTIC TARGET IN OSTEOARTHRITIS: A HYPOTHESIS.

I notice that the abstract is listed as "NA" (not available), which means I cannot provide a meaningful summary of this research paper's methods, findings, or implications.

To write an accurate summary focusing on the study objective, key methods, main findings regarding phenotypes/subgroups, and implications for physiotherapy management, I would need access to the actual abstract content.

If you could provide the complete abstract, I'd be happy to create a concise 3-4 sentence summary in plain language that addresses all the aspects you've requested for this osteoarthritis phenotyping research.

ACTIVATION OF FIBRILLAR COLLAGEN SYNTHESIS AND PHENOTYPIC MODULATION OF CHONDROCYTES IN EARLY HUMAN OSTEOARTHRITIC CARTILAGE LESIONS.

This study aimed to understand how cartilage cells (chondrocytes) change their behavior in the early stages of osteoarthritis by examining collagen production in cartilage samples. Researchers used arthroscopic samples from early osteoarthritis patients and compared them to normal cartilage using advanced tissue analysis techniques including immunohistochemistry and gene expression analysis. The key finding was that early osteoarthritic cartilage showed dramatically increased production of type II collagen (the main cartilage component) and began producing type III collagen, which is not normally found in healthy cartilage, suggesting that cartilage cells undergo significant changes in their cellular identity during early disease stages. These findings suggest that early osteoarthritis involves active cellular responses rather than just passive tissue breakdown, which could inform physiotherapy approaches that support or enhance these natural repair mechanisms during the early stages of the condition.

DIFFERENTIAL EXPRESSION OF MRNAS FOR ENDOPEPTIDASES IN PHENOTYPICALLY MODULATED ('DEDIFFERENTIATED') HUMAN ARTICULAR CHONDROCYTES.

This study investigated how cartilage cells (chondrocytes) change their enzyme production when they lose their normal characteristics and become more like generic connective tissue cells. The researchers cultured human joint cartilage cells in laboratory conditions that caused them to "dedifferentiate" and measured the production of various enzymes that break down cartilage components.

The key finding was that different cartilage-degrading enzymes showed opposite patterns: cathepsins B and L increased dramatically as cells lost their cartilage-like properties, while collagenase-1 decreased, suggesting distinct cellular pathways were activated compared to typical inflammatory responses. This cell transformation (fibroblastic metaplasia) represents a previously unrecognized mechanism by which cartilage cells contribute to joint destruction in osteoarthritis.

These findings suggest that osteoarthritis involves multiple distinct cellular processes beyond inflammation, which could explain why patients respond differently to treatments and supports the need for personalized therapeutic approaches targeting specific disease mechanisms rather than one-size-fits-all interventions.

TWO MUTATIONS WITHIN A FELINE MUCOPOLYSACCHARIDOSIS TYPE VI COLONY CAUSE THREE DIFFERENT CLINICAL PHENOTYPES.

This study aimed to characterize different clinical presentations of mucopolysaccharidosis type VI (MPS VI) in cats caused by two genetic mutations (L476P and D520N) that can occur alone or together. The researchers compared clinical features, enzyme levels, and tissue changes across three genetic combinations in a cat colony used for therapy research. They identified three distinct disease phenotypes: severe MPS VI with dwarfism and facial abnormalities in cats with two copies of L476P, mild disease with normal growth in cats with two copies of D520N, and an intermediate form with normal growth but high rates of joint degeneration in cats with one copy of each mutation. These findings suggest that different genetic combinations of the same disease can produce varying severities of joint problems, which could help inform more personalized treatment approaches and improve understanding of how genetic factors influence the development of degenerative joint disease.

OSTEOBLAST-LIKE CELLS FROM HUMAN SUBCHONDRAL OSTEOARTHRITIC BONE DEMONSTRATE AN ALTERED PHENOTYPE IN VITRO: POSSIBLE ROLE IN SUBCHONDRAL BONE SCLEROSIS.

This study investigated whether bone-building cells (osteoblasts) from osteoarthritis patients have abnormal characteristics that might contribute to the bone thickening (sclerosis) seen under damaged cartilage. Researchers compared bone samples and cultured osteoblast cells from OA patients versus healthy individuals, measuring various cellular activities and protein production. The OA osteoblasts showed an altered phenotype with increased bone-forming activity (higher alkaline phosphatase and osteocalcin), elevated levels of proteins involved in bone remodeling (UPA and IGF-1), but reduced responses to hormonal signals that normally regulate bone metabolism. These findings suggest that abnormal osteoblast behavior may drive subchondral bone changes in OA, indicating that effective physiotherapy and management strategies should consider not just cartilage and muscle factors, but also the underlying bone cell dysfunction when designing treatment approaches for OA patients.

CHONDROCYTE PHENOTYPING IN HUMAN OSTEOARTHRITIS.

This study aimed to characterize chondrocyte (cartilage cell) phenotypes in osteoarthritic cartilage by examining how these cells interact with their surrounding matrix. Researchers used flow cytometry to analyze cell surface molecules on chondrocytes isolated from three zones of cartilage with varying degrees of damage in 10 osteoarthritis patients. The key finding was that chondrocytes from areas with minimal damage showed significantly higher levels of beta1-integrin (a protein that helps cells stick to their surrounding matrix) compared to more severely damaged areas. This suggests that as osteoarthritis progresses, cartilage cells lose their ability to properly communicate with and attach to the surrounding tissue, which may contribute to further cartilage breakdown and could inform targeted rehabilitation strategies that support cartilage cell function.

BONE LOSS AROUND 2 DIFFERENT TYPES OF HIP PROSTHESES.

This study aimed to measure bone loss around hip prostheses using dual energy X-ray absorptiometry (DXA) and compare bone changes between two different prosthesis types. Researchers followed 20 patients with either Bateman or porous-coated anatomic hip prostheses, measuring bone mineral density at multiple time points from 6 to 52 weeks after surgery. The key finding was that patients experienced an average 6% bone loss during this period, with the most severe loss (up to 18%) occurring in the proximal medial cortex area, and no significant difference between the two prosthesis types. These results suggest that substantial bone loss occurs rapidly after hip replacement surgery regardless of prosthesis type, indicating that early post-operative rehabilitation strategies should focus on bone preservation through appropriate weight-bearing and strengthening exercises.

DEDIFFERENTIATED CHONDROCYTES CULTURED IN ALGINATE BEADS: RESTORATION OF THE DIFFERENTIATED PHENOTYPE AND OF THE METABOLIC RESPONSES TO INTERLEUKIN-1BETA.

This study aimed to determine whether chondrocytes (cartilage cells) that had lost their specialized characteristics could regain their normal properties when cultured in alginate beads, and how this affected their response to inflammatory signals. The researchers took chondrocytes that had been expanded in standard culture dishes (causing them to lose their cartilage-like features) and then transferred them to a 3D alginate bead environment, measuring gene expression and responses to interleukin-1β (an inflammatory molecule found in arthritic joints).

The study identified two distinct chondrocyte phenotypes: dedifferentiated cells (which had lost cartilage-specific markers like aggrecan and type II collagen) could be restored to a differentiated state within 2 weeks in alginate culture, regaining their ability to produce cartilage proteins and respond normally to inflammatory signals. Importantly, only the redifferentiated chondrocytes showed proper responses to interleukin-1β, producing nitric oxide and enzymes that break down cartilage matrix, while dedifferentiated cells had impaired responses.

These findings suggest that the cellular state of chondrocytes significantly influences how cartilage responds to inflammation in conditions like osteoarthritis and rheumatoid arthritis, potentially explaining why some patients show different disease progression patterns and treatment responses.

USE OF DIFFERENTIAL SUBTRACTION METHOD TO IDENTIFY GENES THAT CHARACTERIZE THE PHENOTYPE OF CULTURED RHEUMATOID ARTHRITIS SYNOVIOCYTES.

This study aimed to identify genes that distinguish rheumatoid arthritis (RA) synovial cells from osteoarthritis cells to better understand their unique characteristics. Researchers used a differential subtraction method to compare gene expression between cultured RA synovial cells and non-inflammatory osteoarthritis synovial cells, then confirmed their findings with DNA sequencing and Northern blot analysis.

The team identified 24 genes that were differently expressed, with 11 genes consistently overexpressed in RA cells, including those involved in immune cell attraction (chemokines), cell adhesion, and extracellular matrix components. These findings suggest that RA synovial cells have a distinct phenotype that promotes inflammation by facilitating immune cell recruitment and interactions within the joint.

For physiotherapy and management, this research provides insight into the biological differences between RA and osteoarthritis at the cellular level, which could help explain why these conditions respond differently to treatments and may guide the development of more targeted therapeutic approaches for each condition.

IMMUNOLOCALIZATION OF COLLAGEN TYPES II AND III IN SINGLE FIBRILS OF HUMAN ARTICULAR CARTILAGE.

This study aimed to examine the detailed structure of collagen fibers in articular cartilage from patients with osteoarthritis using advanced microscopy techniques. The researchers used immunogold electron microscopy with specialized tissue preparation methods to identify and locate different types of collagen (specifically types II and III) within individual cartilage fibers. They discovered that both collagen types II and III exist together within single cartilage fibers, revealing that these structures are more complex than previously understood, potentially containing up to 11 different collagen types. These findings suggest that osteoarthritis involves intricate changes to cartilage structure at the molecular level, which could inform the development of more targeted physiotherapy approaches and treatments that consider this structural complexity when designing rehabilitation strategies for joint health.

PROTEOGLYCAN PRODUCTION BY IMMORTALIZED HUMAN CHONDROCYTE CELL LINES CULTURED UNDER CONDITIONS THAT PROMOTE EXPRESSION OF THE DIFFERENTIATED PHENOTYPE.

This study aimed to develop reliable cell culture models using immortalized human chondrocytes to investigate how cartilage cells produce proteoglycans (key cartilage components) under different growth conditions. The researchers tested two chondrocyte cell lines derived from juvenile and adult cartilage, examining proteoglycan production under various culture conditions including different cell densities, growth factors, and 3D alginate suspension. They found that both cell lines could produce essential cartilage proteoglycans (aggrecan, decorin, and biglycan), but the ratios and amounts varied significantly depending on culture conditions - with high cell density and growth-promoting conditions generally favoring better proteoglycan production, though 3D alginate culture actually decreased overall production. These findings are important for developing effective cartilage repair strategies and cell-based therapies for osteoarthritis, as they provide insight into how to optimize conditions for chondrocytes to produce the right balance of cartilage components needed for healthy joint function.

STICKLER SYNDROME AND VITREORETINAL DEGENERATION: CORRELATION BETWEEN LOCUS MUTATION AND VITREOUS PHENOTYPE. APROPOS OF A CASE.

This study aimed to investigate the relationship between genetic mutations and eye characteristics in an Italian family with Stickler syndrome, a hereditary condition affecting connective tissues including joints and eyes. The researchers examined five family members with symptoms including severe nearsightedness, joint problems, and characteristic facial features, then performed genetic testing to identify which gene was responsible for their condition. The key finding was that while the family had mutations in the COL11A1 gene, they showed a "membranous" eye pattern (Type 1) rather than the expected "beaded" pattern (Type 2) previously associated with this genetic variant. This discovery suggests that Stickler syndrome has more varied presentations than previously understood, which could help clinicians better diagnose patients and indicates that genetic testing may be more important than visual eye examination alone for determining the specific type of Stickler syndrome and guiding appropriate management strategies.

FORMATION AND PHENOTYPE OF CELL CLUSTERS IN OSTEOARTHRITIC MENISCUS.

This study aimed to understand how cell clusters form in the meniscus during early osteoarthritis and to identify the characteristics of these clustered cells. The researchers used a rabbit model where the ACL was cut to induce osteoarthritis, then examined meniscus tissue under a microscope using special stains to identify cell types, proliferation, and tissue changes.

The study found that after ACL injury, normal meniscus cells became isolated into distinct clusters with three different appearances: star-shaped cells only, mixed star-shaped and round cells, or round cells only. Over time, clusters containing only round cells became more prominent and grew larger due to cell multiplication, and these areas showed calcium deposits and expressed type X collagen (a marker associated with cartilage breakdown).

These findings suggest that meniscal cell clusters in osteoarthritis develop through a predictable pattern and behave similarly to the problematic cells seen in damaged joint cartilage. For physiotherapy and management, this research helps explain the biological processes underlying meniscal degeneration in osteoarthritis, potentially informing future treatments that could target these cellular changes to slow disease progression.

TARGETED DISRUPTION OF COL11A2 PRODUCES A MILD CARTILAGE PHENOTYPE IN TRANSGENIC MICE: COMPARISON WITH THE HUMAN DISORDER OTOSPONDYLOMEGAEPIPHYSEAL DYSPLASIA (OSMED).

This study aimed to investigate the effects of disrupting the COL11A2 gene (which produces a component of cartilage collagen) in transgenic mice and compare the results to human genetic disorders affecting cartilage development.

The researchers used genetic engineering techniques to create mice that could not produce functional alpha2(XI) collagen chains, then analyzed their cartilage structure, growth patterns, and physical characteristics over their lifetime.

The mice developed a relatively mild cartilage disorder characterized by smaller body size, facial abnormalities including shorter nasal bones, hearing loss, and disorganized growth plate cartilage in long bones, but importantly did not develop obvious osteoarthritis even at one year of age.

These findings suggest that COL11A2 mutations create distinct cartilage phenotypes with primarily developmental rather than degenerative effects, which has implications for understanding certain genetic forms of cartilage disorders in humans and suggests that patients with similar genetic profiles may not necessarily develop early osteoarthritis requiring intensive joint protection strategies.

[COMPUTER-ASSISTED NAVIGATED CUP PLACEMENT OF DIFFERENT CUP TYPES IN HIP ARTHROPLASTY--A RANDOMISED CONTROLLED TRIAL].

This study aimed to compare how different types of acetabular cups (the socket part of hip replacements) behave during computer-navigated surgery and affect surgical precision. Researchers conducted a randomized trial with 80 hip replacement surgeries, comparing two uncemented cup designs (press-fit and screw cups) and cemented cups, while using computer navigation to track cup positioning throughout surgery.

The study found distinct "behavioral phenotypes" among cup types: press-fit cups showed the highest variability in positioning (standard deviation 3.86°), screw cups had moderate variability (2.1°), and cemented cups were most stable (0.84°), with significant differences particularly in the anteversion angle during insertion. The spherical press-fit design was most susceptible to positional changes during implantation.

These findings suggest that cup design significantly influences surgical outcomes and that computer-assisted navigation systems can help surgeons compensate for these inherent design differences, potentially improving implant positioning accuracy and long-term patient outcomes.

PHENOTYPIC EXPRESSION OF OSTEOBLAST COLLAGEN IN OSTEOARTHRITIC BONE: PRODUCTION OF TYPE I HOMOTRIMER.

This study investigated the quality and structure of collagen in bone tissue from osteoarthritic femurs compared to healthy controls. The researchers analyzed collagen composition in subchondral bone (the bone layer beneath joint cartilage) and discovered that osteoarthritic bone produces an abnormal type of collagen called type I homotrimer, which had not been previously identified in osteoarthritis. This altered collagen creates weaker, more disorganized bone structure with reduced mechanical strength and poor mineralization in the femoral head (hip joint). These findings suggest that bone changes may play a crucial role in osteoarthritis development and progression, potentially informing rehabilitation approaches that consider not just cartilage health but also the underlying bone quality when designing exercise and treatment programs for hip osteoarthritis patients.

COMPARISON OF THE INHIBITORY EFFECTS OF TWO TYPES (90 KDA AND 190 KDA) OF HYALURONIC ACID ON THE EXPRESSION OF FIBRINOLYTIC FACTORS IN HUMAN SYNOVIAL FIBROBLASTS.

This study aimed to compare how two different molecular weights of hyaluronic acid (90 kDa and 190 kDa) affect fibrinolytic factors in synovial tissue cells from patients with osteoarthritis and rheumatoid arthritis. The researchers cultured synovial fibroblasts from both patient groups and tested how each type of hyaluronic acid influenced the production and activity of enzymes involved in tissue breakdown and inflammation.

The key finding was that both types of hyaluronic acid reduced harmful fibrinolytic activity, but the higher molecular weight version (190 kDa) was more effective than the lower weight version (90 kDa). Additionally, the treatments showed different response patterns between the two arthritis types - osteoarthritis cells responded better to reduced enzyme secretion, while rheumatoid arthritis cells showed greater reduction in enzyme receptors.

These results suggest that higher molecular weight hyaluronic acid injections may be more beneficial for managing joint inflammation and tissue breakdown in arthritis patients, with potential differences in effectiveness between osteoarthritis and rheumatoid arthritis that could inform personalized treatment approaches.

[PHENOTYPING OF CHONDROCYTES FROM HUMAN OSTEOARTHRITIC CARTILAGE: CHONDROCYTE EXPRESSION OF BETA INTEGRINS AND CORRELATION WITH ANATOMIC INJURY].

This study aimed to investigate how chondrocytes (cartilage cells) from osteoarthritic joints express different adhesion molecules called integrins, and whether this expression varies with the severity of cartilage damage. The researchers used flow cytometry to analyze integrin expression in chondrocytes isolated from three zones of varying damage severity in knee cartilage from 10 osteoarthritis patients undergoing joint replacement surgery.

The key finding was that integrin expression (particularly beta1 integrin and various alpha chains) decreased progressively from less damaged to more severely damaged cartilage zones, while cell proliferation increased in the most damaged areas. This suggests that osteoarthritis involves distinct chondrocyte phenotypes or subgroups based on damage severity, with cells in severely damaged regions showing altered adhesion molecule profiles and increased attempts at repair through proliferation.

These findings indicate that the cellular response to cartilage damage is not uniform across the joint, suggesting that rehabilitation strategies might need to consider the heterogeneous nature of cartilage degeneration and that different regions may respond differently to mechanical loading or other therapeutic interventions.

CLINICAL PHENOTYPE AND MOLECULAR DIAGNOSIS OF MULTIPLE EPIPHYSEAL DYSPLASIA WITH RELATIVE HIP SPARING DURING CHILDHOOD (EDM2).

This study investigated the clinical features and genetic cause of a specific subtype of multiple epiphyseal dysplasia (EDM2) that spares the hips during childhood in a large family spanning four generations. The researchers used genetic screening to identify mutations and examined cartilage samples under electron microscopy from 19 family members, 12 of whom were affected. They identified a novel mutation in the COL9A2 gene that affects collagen production and confirmed this genetic change in both symptomatic patients and presymptomatic children, establishing a distinct phenotype characterized by knee, ankle, elbow, and finger joint problems while hip joints remain relatively unaffected in early years. The findings suggest that genetic testing for COL9A2 mutations could help diagnose this specific subtype of joint disease early, allowing for targeted lifestyle modifications and appropriate family counseling to manage the progression to early arthritis and joint complications.

FRACTURE OF THE RADIAL HEAD AND NECK OF MASON TYPES II AND III DURING GROWTH: A 14-25 YEAR FOLLOW-UP.

This study aimed to evaluate the long-term outcomes of radial head and neck fractures (Mason types II and III) that occurred during childhood growth. The researchers examined 24 individuals at an average of 19 years after their childhood injury, comparing their injured and uninjured elbows and assessing pain, function, and development of osteoarthritis.

The main finding was that childhood radial head/neck fractures have excellent long-term outcomes regardless of treatment method - 86% of patients had no complaints and none developed elbow osteoarthritis, though there was a small decrease in elbow flexion (3 degrees) compared to the uninjured side.

This suggests that these fractures during growth have a favorable prognosis and low risk of developing osteoarthritis, which has important implications for patient counseling and may support less aggressive treatment approaches. For physiotherapy, the findings indicate that maintaining elbow flexion range of motion should be a focus during rehabilitation of these pediatric fractures.

PHENOTYPIC CHARACTERIZATION OF INFLAMMATORY CELLS FROM OSTEOARTHRITIC SYNOVIUM AND SYNOVIAL FLUIDS.

This study aimed to investigate the role of inflammatory cells in osteoarthritis (OA) progression, challenging the traditional view of OA as purely a "wear-and-tear" condition. Researchers analyzed synovial fluid and tissue samples from OA patients using laboratory techniques including cell analysis, tissue staining, and cell culture experiments. The study found that two-thirds of tissue samples showed significant T cell infiltration, particularly around blood vessels and in cellular clusters, with these immune cells displaying activated characteristics and producing inflammatory signals. These findings suggest that OA involves distinct inflammatory phenotypes that could be targeted with anti-inflammatory treatments, potentially offering physiotherapists and clinicians new approaches beyond mechanical interventions for managing joint pain and disease progression.

QUANTIFICATION OF EXPRESSION LEVELS OF CELLULAR DIFFERENTIATION MARKERS DOES NOT SUPPORT A GENERAL SHIFT IN THE CELLULAR PHENOTYPE OF OSTEOARTHRITIC CHONDROCYTES.

This study aimed to investigate whether chondrocytes (cartilage cells) undergo a fundamental change in cellular identity during osteoarthritis development. The researchers used quantitative PCR to measure expression levels of different collagen types (markers of cell differentiation) in normal, early degenerative, and late-stage osteoarthritic cartilage samples. While they confirmed that osteoarthritic chondrocytes show dramatically increased synthetic activity compared to normal cartilage, the ratios between different collagen types remained largely unchanged, indicating that the cells maintain their original chondrocyte identity rather than transforming into other cell types. These findings suggest that osteoarthritic chondrocytes represent activated rather than fundamentally altered cells, which supports rehabilitation approaches focused on optimizing the mechanical environment to promote appropriate chondrocyte activity rather than attempting to reverse cellular dedifferentiation.

SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY LEPTODACTYLIC FORM: CLINICAL COURSE AND PHENOTYPIC VARIATIONS IN FOUR PATIENTS.

This study aimed to describe the clinical features and variations of spondyloepimetaphyseal dysplasia with joint laxity (a rare genetic bone disorder) by examining four patients aged 5-33 years. The researchers used detailed clinical examinations and radiological imaging to document the progression of symptoms and bone changes over time. Key findings showed that patients developed multiple joint problems due to severe joint looseness, including spinal curvature, hip and knee dislocations, and progressive joint deformities, with bone development abnormalities that eventually led to early arthritis. For physiotherapy management, these patients require specialized care focusing on joint stabilization, muscle strengthening to compensate for loose joints, and careful monitoring to prevent progressive deformities while avoiding overstressing unstable joints.

CEMENTLESS TOTAL HIP ARTHROPLASTY USING POROUS-COATED BIOMET ACETABULAR CUPS (HEXLOC AND RINGLOC TYPES).

This study aimed to evaluate the mid-term outcomes of two types of cementless hip replacement systems (Hexloc and Ringloc acetabular cups) in 58 patients followed for an average of 6 years and 10 months. The researchers measured polyethylene wear rates and analyzed factors associated with osteolysis (bone breakdown around the implant) by examining patient age, implant design features, and liner thickness. Key findings revealed that patients who developed osteolysis had significantly higher annual wear rates (0.18 mm/year vs 0.10 mm/year), and the two cup types showed different wear patterns - Hexloc cups were more influenced by patient age and liner thickness, while Ringloc cups showed more consistent wear regardless of these factors. These results suggest that implant selection for hip replacement should consider patient age and specific design characteristics, with implications for predicting long-term outcomes and potentially guiding rehabilitation protocols based on expected implant performance.

HIGH MIGRATION RATE OF TWO TYPES OF THREADED ACETABULAR CUPS.

This study compared the performance of two types of threaded hip replacement cups (Link V-type and a modified Bad Bramstedt version) in patients with different conditions including osteoarthritis, inflammatory arthritis, and hip dysplasia. The researchers tracked 479 Link cups for an average of 8.6 years and 110 modified cups for 4.5 years, measuring cup movement (migration) and survival rates using radiographic analysis. Both cup types showed concerning high migration rates (cup movement >3mm or tilting >5°) in 73% of original Link cups and 39% of modified cups, with longer follow-up time and initial cup positioning being key factors affecting migration. Due to these poor results with excessive cup loosening, both threaded cup designs were discontinued in favor of press-fit cups, highlighting the importance of implant selection in hip replacement surgery for osteoarthritis patients.

A ROLE FOR CHEMOKINES IN THE INDUCTION OF CHONDROCYTE PHENOTYPE MODULATION.

This laboratory study investigated how chemokines (cell signaling proteins) affect the behavior and characteristics of chondrocytes, the cells that maintain cartilage in our joints. Researchers used flow cytometry and cell culture techniques to examine how specific chemokines influence chondrocyte function, including their ability to multiply, produce enzymes, and change their cellular properties.

The study found that human chondrocytes express several chemokine receptors (CXCR3, CXCR4, CXCR5, and CCR6), and when stimulated by their corresponding chemokines, the cells increased production of matrix-degrading enzymes (MMPs and other enzymes that break down cartilage) and showed enhanced cell proliferation. This suggests that chemokines can push chondrocytes toward a more destructive, proliferative phenotype rather than their normal cartilage-maintaining role.

These findings indicate that chemokine signaling pathways could be important targets for osteoarthritis treatment, as they appear to drive cartilage breakdown processes. For physiotherapy and rehabilitation, this research suggests that interventions aimed at reducing inflammatory chemokine activity (through exercise, manual therapy, or other anti-inflammatory approaches) might help preserve the healthy, cartilage-maintaining phenotype of chondrocytes and slow joint degeneration.

DOWN-REGULATION OF THE GTPASE RHOB MIGHT BE INVOLVED IN THE PRE-APOPTOTIC PHENOTYPE OF OSTEOARTHRITIC CHONDROCYTES.

This study investigated the role of RhoB protein in cartilage cells (chondrocytes) to understand what goes wrong in osteoarthritis. The researchers used laboratory techniques to compare RhoB levels in healthy versus osteoarthritic cartilage samples, and tested how cartilage cells respond to inflammatory signals in controlled experiments. They found that RhoB protein levels were significantly lower in osteoarthritic cartilage compared to healthy cartilage, and that this protein appears essential for normal cartilage cell survival and function. The findings suggest that reduced RhoB may contribute to cartilage cell dysfunction and death in osteoarthritis, which could represent a specific disease subtype characterized by particular cellular changes, though this research is still at the basic science level and doesn't directly translate to specific physiotherapy approaches yet.

INFLUENCE OF RADIOGRAPHIC PHENOTYPE ON RISK OF HIP OSTEOARTHRITIS WITHIN FAMILIES.

This study aimed to determine whether genetic risk for hip osteoarthritis varies depending on different radiographic patterns of the disease within families. Researchers analyzed X-rays from 331 families where one sibling had hip replacement surgery, comparing radiographic features (particularly bone migration patterns and osteophyte formation) between affected siblings and their family members, as well as with the general population.

The key finding was that siblings of patients who had hip osteoarthritis with poor bone response (no osteophyte formation) had twice the risk of developing definite hip OA and three times higher risk of needing hip replacement compared to siblings whose family member had osteophytes. Interestingly, the specific patterns of bone changes were not consistent within families, even among same-sex siblings.

These findings suggest that hip osteoarthritis involves distinct genetic subtypes, with the "poor bone response" phenotype carrying higher familial risk, which could help inform early screening strategies and targeted prevention approaches in physiotherapy and rehabilitation for high-risk family members.

ENUMERATION AND PHENOTYPIC CHARACTERIZATION OF SYNOVIAL FLUID MULTIPOTENTIAL MESENCHYMAL PROGENITOR CELLS IN INFLAMMATORY AND DEGENERATIVE ARTHRITIS.

This study aimed to identify and characterize mesenchymal progenitor cells (MPCs) in the joint fluid of patients with different types of arthritis, comparing their properties to bone marrow cells. Researchers analyzed synovial fluid from 100 patients with rheumatoid arthritis (RA), osteoarthritis (OA), and other joint conditions, using laboratory techniques to grow and test these cells' ability to develop into different tissue types.

The key finding was that patients with osteoarthritis had significantly more MPCs in their joint fluid (37 cells per milliliter) compared to those with rheumatoid arthritis (only 2 cells per milliliter), while the cells from both conditions showed similar regenerative potential. The researchers suggest that the higher number of these repair cells in osteoarthritis likely comes from damaged joint structures breaking down and releasing cells into the joint fluid.

These findings indicate that osteoarthritis and inflammatory arthritis represent distinct disease phenotypes with different cellular repair mechanisms, which could influence how physiotherapy and other treatments are tailored for each condition.

SKELETAL DYSPLASIAS AND THE OSTEOARTHRITIC PHENOTYPE.

This study examined the distinct characteristics of precocious (early-onset) osteoarthritis that occurs as part of skeletal dysplasias, comparing it to typical late-onset osteoarthritis. The authors used a descriptive approach to analyze the clinical features and inheritance patterns of osteoarthritis associated with various rare skeletal disorders. They found that precocious osteoarthritis represents an aggressive phenotype that progresses rapidly, often includes both joint and non-joint symptoms not seen in classic osteoarthritis, and typically follows Mendelian inheritance patterns. These findings suggest that patients with early-onset osteoarthritis secondary to skeletal dysplasias may require specialized management approaches that account for their more severe disease progression and broader symptom profile compared to standard osteoarthritis treatment protocols.

MODULATION OF THE PHENOTYPIC AND FUNCTIONAL PROPERTIES OF PHAGOCYTIC MACROPHAGES BY WEAR PARTICLES FROM ORTHOPAEDIC IMPLANTS.

This study investigated the inflammatory response around failed joint implants by examining different types of immune cells (macrophages) that accumulate at the bone-implant interface. Researchers used specialized antibodies to identify distinct macrophage subgroups in tissue samples from 17 patients undergoing revision surgery, comparing these to samples from rheumatoid arthritis and osteoarthritis patients.

The key finding was that metal wear particles from implants triggered a much stronger immune response than plastic (polyethylene) particles, with 80% of macrophages showing an activated, antigen-presenting phenotype around metal debris compared to only 30% around plastic debris. This suggests that metal particles are more likely to cause sustained inflammation and immune system activation that can lead to bone destruction around implants.

These results indicate that the type of wear debris significantly influences the inflammatory phenotype, with metal particles creating a more aggressive immune environment. For clinical management, this suggests that implant material selection and strategies to minimize metal particle generation may be important for preventing implant failure, though this research focuses on the underlying biology rather than direct rehabilitation implications.

RETROVIRAL TRANSDUCTION WITH SOX9 ENHANCES RE-EXPRESSION OF THE CHONDROCYTE PHENOTYPE IN PASSAGED OSTEOARTHRITIC HUMAN ARTICULAR CHONDROCYTES.

This study investigated whether introducing the SOX9 gene into cartilage cells (chondrocytes) from osteoarthritic joints could restore their ability to produce healthy cartilage tissue. Researchers used gene therapy techniques to add SOX9 to chondrocytes from both healthy and osteoarthritic joints, then grew them in laboratory conditions with various growth factors to test cartilage formation.

The key finding was that osteoarthritic chondrocytes responded similarly to healthy chondrocytes when treated with SOX9 - both cell types regained their ability to produce cartilage proteins (collagen II) and other cartilage components, especially when combined with specific growth factors. Importantly, the study revealed that osteoarthritis does not permanently damage the cartilage cells' fundamental capacity to behave normally.

These results suggest that cartilage cells in osteoarthritic joints retain their potential for repair and regeneration, which could inform new treatment approaches focused on reactivating the cells' natural cartilage-forming abilities rather than just managing symptoms.

IN VIVO CARTILAGE DEFORMATION AFTER DIFFERENT TYPES OF ACTIVITY AND ITS DEPENDENCE ON PHYSICAL TRAINING STATUS.

This study aimed to understand how knee cartilage deforms during different physical activities and whether training status affects these responses in healthy individuals. Researchers used MRI and 3D imaging to measure cartilage volume changes before and after various activities (knee bends, squatting, walking, running, cycling) in the kneecap and knee joint, comparing professional athletes to untrained volunteers.

The findings revealed that cartilage deformation varied by activity intensity, with knee bends causing the greatest kneecap cartilage compression (-5.9%) and normal walking the least (-2.8%), while knee joint cartilage only showed significant deformation during high-impact activities (-7%). Importantly, no differences in cartilage deformation were found between trained athletes and untrained individuals, suggesting that adult cartilage properties cannot be improved through training.

These results indicate that cartilage responds predictably to mechanical loading regardless of fitness level, which has important implications for understanding osteoarthritis development and designing rehabilitation programs that consider the mechanical demands placed on different parts of the knee joint.

ASSESSMENT OF POSTERIOR STABILITY IN TOTAL KNEE REPLACEMENT BY STRESS RADIOGRAPHS: PROSPECTIVE COMPARISON OF TWO DIFFERENT TYPES OF MOBILE BEARING IMPLANTS.

This study aimed to compare the posterior stability of two different mobile bearing total knee replacement designs using stress X-rays in patients who had their posterior cruciate ligament removed during surgery. The researchers followed 34 patients with knee osteoarthritis who received either a Duracon or Genesis prosthesis, measuring posterior tibial translation (backward movement of the shin bone) through kneeling X-rays before and after surgery.

Both implant types showed significant backward movement of the tibia after surgery compared to before surgery, but there were no differences in stability or clinical outcomes between the two designs. The findings suggest that while removing the posterior cruciate ligament and using deep-dish mobile bearing inserts has surgical advantages, both implant types allow considerable posterior movement during knee flexion.

For physiotherapy and rehabilitation, this indicates that patients with either type of mobile bearing knee replacement may experience similar knee mechanics and stability, requiring comparable rehabilitation approaches focused on strengthening and functional training regardless of the specific implant design used.

IMPACT OF TWO TYPES OF EXPECTANCY ON RECOVERY FROM TOTAL KNEE REPLACEMENT SURGERY (TKR) IN ADULTS WITH OSTEOARTHRITIS.

This study aimed to examine how psychological factors—specifically future expectations and self-efficacy beliefs—influence recovery outcomes following total knee replacement surgery in adults with osteoarthritis. Researchers followed TKR patients and controls over 6 months, collecting validated outcome measures (SF-36, WOMAC, clinical assessments) before surgery, at 4-6 weeks, and at 6 months post-surgery. The study found that while TKR patients showed significant improvements in physical health compared to controls, patients' pre-surgery expectations and self-efficacy beliefs predicted 9-13% of the variance in both physical and mental health recovery outcomes. These findings suggest that identifying patients with different psychological profiles (high vs. low expectations/self-efficacy) could help physiotherapists tailor rehabilitation approaches and potentially improve post-surgical outcomes through targeted interventions that address psychological readiness for recovery.

INTRAJOINT COMPARISONS OF GENE EXPRESSION PATTERNS IN HUMAN OSTEOARTHRITIS SUGGEST A CHANGE IN CHONDROCYTE PHENOTYPE.

This study aimed to compare gene expression patterns between mildly and severely damaged cartilage areas within the same knee joint in osteoarthritis patients. The researchers collected cartilage samples from both minimal and advanced OA regions in the same patients, then analyzed tissue structure and measured the expression of nine genes involved in cartilage health and breakdown using molecular techniques.

The study identified distinct molecular phenotypes between cartilage regions, with severely damaged areas showing increased osteopontin (a bone-related protein) but decreased levels of most cartilage-building genes including aggrecan, SOX9, and BCL-2. The researchers also confirmed that BCL-2 (a cell survival gene) correlates with both SOX9 and aggrecan expression, suggesting these genes work together to maintain healthy cartilage.

These findings suggest that different areas within the same arthritic joint represent distinct disease phenotypes with different molecular characteristics. For physiotherapy and rehabilitation, this implies that treatments may need to consider that osteoarthritis affects joints unevenly, and interventions targeting cartilage preservation might be most beneficial when applied early before the shift to the more severe molecular phenotype occurs.

SUBCHONDRAL BONE OSTEOBLASTS INDUCE PHENOTYPIC CHANGES IN HUMAN OSTEOARTHRITIC CHONDROCYTES.

This study investigated how different types of bone cells beneath joint cartilage affect the behavior of cartilage cells (chondrocytes) in osteoarthritis. The researchers cultured human chondrocytes from osteoarthritic joints either alone or together with bone cells (osteoblasts) from two different zones: normal (non-sclerotic) and hardened/thickened (sclerotic) subchondral bone areas, then measured gene expression changes over 4-10 days.

The findings revealed distinct osteoarthritis phenotypes based on the source of bone cells - sclerotic osteoblasts caused more dramatic harmful changes in chondrocytes compared to normal osteoblasts, significantly reducing the expression of healthy cartilage markers (SOX9, collagen II) while increasing bone formation signals (OSF-1). Additionally, sclerotic osteoblasts disrupted important cartilage maintenance pathways by reducing PTHrP signaling, which normally helps preserve cartilage health.

These results suggest that the hardened bone beneath damaged cartilage actively contributes to cartilage breakdown by pushing cartilage cells toward an abnormal, hypertrophic state that promotes further joint deterioration. For physiotherapy and rehabilitation, this highlights the importance of targeting subchondral bone health through weight-bearing exercises and interventions that may help prevent or slow the progression of these harmful

IS THERE AN ASSOCIATION BETWEEN THE USE OF DIFFERENT TYPES OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND RADIOLOGIC PROGRESSION OF OSTEOARTHRITIS? THE ROTTERDAM STUDY.

This study aimed to investigate whether different types of nonsteroidal anti-inflammatory drugs (NSAIDs) affect the progression of hip and knee osteoarthritis over time. Researchers followed 1,695 people (for hip analysis) and 635 people (for knee analysis) aged 55+ for an average of 6.6 years, comparing X-ray changes and using statistical analysis to examine the relationship between NSAID use and joint deterioration.

The key finding was that people using diclofenac for more than 180 days had a 2.4 times higher risk of hip osteoarthritis progression and 3.2 times higher risk of knee osteoarthritis progression compared to short-term users, suggesting this particular NSAID may accelerate joint damage. For physiotherapy and osteoarthritis management, these results highlight the importance of considering long-term NSAID effects when developing treatment plans, potentially emphasizing non-drug approaches like exercise therapy and pain management strategies to reduce reliance on medications that may worsen joint health over time.

POLYARTICULAR OSTEOARTHRITIS--TWO MAJOR PHENOTYPES HYPOTHESIZED.

This study proposes a theoretical framework to classify polyarticular osteoarthritis (POA) into two distinct phenotypes based on joint involvement patterns and underlying genetics. The authors used clinical observation and genetic theory to hypothesize that Type 1 POA involves finger nodes, knee (inner compartment), and big toe joints (the traditional "nodal generalized" pattern), while Type 2 POA affects index/middle finger knuckles, elbows, ankles, and foot joints - similar to the pattern seen in hereditary hemochromatosis. The key finding is the proposed link between Type 2 POA and mutations in the HFE gene (associated with iron metabolism disorders), suggesting that iron overload may contribute to this specific osteoarthritis pattern. These proposed phenotypes could help physiotherapists and clinicians better predict disease progression and tailor joint-specific treatment approaches, though the hypothesis requires validation through genetic testing and clinical studies.

MACROPHAGE-LIKE SYNOVIOCYTES DISPLAY PHENOTYPIC POLYMORPHISMS IN A SERUM-FREE TISSUE-CULTURE MEDIUM.

This study aimed to develop a better method for studying synovial macrophages from osteoarthritis patients by comparing traditional serum-containing culture medium with a new serum-free approach. The researchers cultured synovial tissue from 11 osteoarthritis patients in both conditions and analyzed cell markers and inflammatory molecules over 2-3 weeks.

The key finding was that serum-free culture preserved distinct macrophage-like cell types (phenotypes) much better than traditional methods - with over 80% of cells showing macrophage markers compared to only 14% in serum-containing cultures. The serum-free method prevented unwanted fibroblast activation that typically occurs in standard culture conditions, allowing researchers to study the true diversity of synovial macrophage subtypes.

This improved culture technique could help researchers better understand the different roles that various macrophage phenotypes play in osteoarthritis, potentially leading to more targeted treatments and informing physiotherapy approaches based on individual patients' inflammatory profiles.

INTRAFAMILIAL PHENOTYPIC DIVERSITY IN MULTIPLE EPIPHYSEAL DYSPLASIA ASSOCIATED WITH A COL9A2 MUTATION (EDM2).

This study examined the varying symptoms and severity within a Japanese family of five members who all carried the same genetic mutation (COL9A2) causing multiple epiphyseal dysplasia, a condition affecting bone growth at joints. Researchers used genetic testing to confirm the mutation and X-rays to assess joint abnormalities across different family members ranging from 9 to 65 years old. Despite sharing the same genetic defect, family members showed dramatically different presentations - from severe wrist and knee deformities in the youngest boy requiring surgical limb lengthening, to mild symptoms in his brother, to primarily knee osteoarthritis in the adult relatives with no wrist problems. These findings highlight that individuals with the same genetic mutation can have vastly different symptoms and severity, suggesting that physiotherapy and management approaches for multiple epiphyseal dysplasia may need to be highly individualized rather than following a standard protocol based solely on genetic diagnosis.

EXPANSION ON SPECIFIC SUBSTRATES REGULATES THE PHENOTYPE AND DIFFERENTIATION CAPACITY OF HUMAN ARTICULAR CHONDROCYTES.

This study investigated how growing human cartilage cells (chondrocytes) on different surface materials affects their characteristics and ability to develop into different cell types. Researchers expanded chondrocytes from five donors on three different substrates: plastic dishes, collagen type II-coated dishes, and ceramic material-coated slides, then assessed their properties and differentiation capacity.

The key findings revealed distinct cellular phenotypes based on the expansion substrate: cells grown on collagen type II maintained better cartilage-like characteristics and showed enhanced ability to form cartilage tissue, while cells grown on ceramic developed more bone-like properties and improved capacity for bone formation. Compared to standard plastic surfaces, collagen-expanded cells produced 2.3-fold higher cartilage markers and 1.7-fold more cartilage matrix components, whereas ceramic-expanded cells showed 22.6-fold higher bone markers.

These substrate-induced changes may represent different stages of osteoarthritis progression, suggesting that understanding how cartilage cells respond to their environment could inform targeted rehabilitation strategies and tissue engineering approaches for treating cartilage damage.

COMBINED HIGH-RESOLUTION MAGNETIC RESONANCE IMAGING AND HISTOLOGICAL EXAMINATION TO EXPLORE THE ROLE OF LIGAMENTS AND TENDONS IN THE PHENOTYPIC EXPRESSION OF EARLY HAND OSTEOARTHRITIS.

This study aimed to understand how ligaments and tendons influence the early development and appearance of hand osteoarthritis by combining advanced MRI imaging with detailed tissue examination. Researchers used high-resolution MRI to examine finger joints in 20 patients with early osteoarthritis (within 12 months of onset) and compared findings with microscopic analysis of cadaver hand specimens. The key finding was that collateral ligaments and tendons play a central role in determining where bone swelling, erosions, and characteristic nodes develop in early hand osteoarthritis - essentially acting as the "directors" of how the disease manifests in different joint locations. These findings suggest that physiotherapy and management strategies for early hand osteoarthritis should consider the mechanical stresses and loading patterns of specific ligaments and tendons, potentially leading to more targeted interventions that address these soft tissue structures rather than focusing solely on joint cartilage.

[LUMBAR DISC ARTHROPLASTY: INDICATIONS, BIOMECHANICS, TYPES, AND RADIOLOGICAL CRITERIA].

This study aimed to review the indications, biomechanics, and radiological criteria for lumbar total disc replacement (TDR) as an alternative to spinal fusion surgery for treating painful degenerative disc disease. The authors examined clinical outcomes and described comprehensive imaging protocols including X-rays, CT scans, MRI, and bone density measurements to properly select patients and assess treatment results. Key findings showed that TDR patients experienced significant improvements in back pain and disability scores, with faster initial recovery compared to fusion surgery, but success depends heavily on careful patient selection using specific radiological criteria to exclude conditions like facet joint arthritis or bone quality issues. For physiotherapy practice, this suggests that patients with TDR may benefit from accelerated rehabilitation protocols compared to fusion patients, though treatment should be tailored based on the specific spinal pathology identified through detailed imaging assessment.

DIFFERENT LOSS OF BMD USING UNCEMENTED PRESS-FIT AND WHOLE POLYETHYLENE CUPS FIXED WITH CEMENT: REPEATED DXA STUDIES IN 96 HIPS RANDOMIZED TO 3 TYPES OF FIXATION.

This study aimed to compare bone mineral density (BMD) changes around different types of hip replacement cup fixation methods to understand complications like loosening and bone loss. Researchers used DXA scans to measure bone density around the hip socket in 96 hips at 1 week, 12 months, and 24 months after surgery, comparing three fixation types: two cemented cup methods and one uncemented press-fit cup. The key finding was that patients with uncemented cups showed significantly greater bone loss in the areas above and beside the cup after 2 years compared to those with cemented cups, while the two cemented methods performed similarly. This suggests that uncemented cups may cause "stress shielding" (where the implant takes load away from bone, causing it to weaken), potentially leading to the bone destruction problems commonly seen with this fixation type, though longer studies are needed to confirm this relationship.

PRIMARY OSTEOARTHRITIS IN THE ANKLE JOINT IS ASSOCIATED WITH FINGER METACARPOPHALANGEAL OSTEOARTHRITIS AND THE H63D MUTATION IN THE HFE GENE: EVIDENCE FOR A HEMOCHROMATOSIS-LIKE POLYARTICULAR OSTEOARTHRITIS PHENOTYPE.

This study investigated whether genetic mutations associated with hemochromatosis (iron overload disease) might be linked to primary ankle osteoarthritis. Researchers examined 13 patients with primary ankle OA and 6 with secondary (injury-related) ankle OA, conducting genetic testing for HFE gene mutations and assessing other joints for arthritis patterns.

The study found that 11 of 13 patients with primary ankle OA carried HFE gene mutations (particularly H63D), compared to much lower rates in secondary ankle OA patients and the general population. Additionally, 7 of these patients also had osteoarthritis in their finger knuckle joints (metacarpophalangeal joints), creating a distinctive pattern similar to that seen in hemochromatosis-related arthritis.

The findings suggest a new "Type 2" osteoarthritis subtype characterized by ankle and finger knuckle involvement, linked to specific genetic mutations but without actual iron overload. This discovery could help physiotherapists and clinicians recognize patients who may develop this particular multi-joint arthritis pattern, potentially allowing for earlier intervention and more targeted management strategies for this distinct OA phenotype.

IMMORTALIZED CELL LINES FROM MOUSE XIPHISTERNUM PRESERVE CHONDROCYTE PHENOTYPE.

This study aimed to develop and characterize immortalized chondrocyte cell lines from mouse xiphisternum (chest cartilage) as research tools for studying cartilage biology and osteoarthritis. The researchers used cell culture techniques and molecular analysis to test how these cells responded to different treatments, including bone morphogenetic protein-2 (BMP-2) and inflammatory factor IL-1, in both standard flat cultures and 3D alginate bead systems.

The key finding was that these cell lines maintained their chondrocyte characteristics, producing cartilage-specific proteins like collagen type II and aggrecan when stimulated with BMP-2, while showing cartilage breakdown responses (increased enzymes that destroy cartilage matrix) when exposed to IL-1. This demonstrates the cells preserved both their normal cartilage-building functions and their disease-related destructive responses.

These validated cell lines provide researchers with a reliable laboratory model to study how chondrocytes behave in health and disease, potentially leading to better understanding of osteoarthritis mechanisms and development of targeted treatments, though direct clinical applications for physiotherapy are not yet apparent from this basic research.

THE USE OF ILIZAROV TECHNIQUE AND OTHER TYPES OF EXTERNAL FIXATION FOR THE TREATMENT OF INTRA-ARTICULAR CALCANEAL FRACTURES.

This study examines the use of Ilizarov technique and other external fixation methods for treating severe calcaneal (heel bone) fractures that extend into the joint space. The researchers focused on minimally invasive closed treatment approaches using ring-type fine-wire external fixation devices as alternatives to traditional open surgery with internal plates and screws. The study highlights that severely fragmented calcaneal fractures represent a distinct subgroup of injuries with high soft tissue compromise that pose significant treatment challenges. The findings suggest that external fixation techniques may offer important management advantages for this specific fracture phenotype, potentially reducing complications like wound problems, infection, and post-traumatic osteoarthritis compared to conventional surgical approaches, which could lead to better long-term outcomes for physiotherapy and rehabilitation.

THE GENETICS OF GENERALIZED OSTEOARTHRITIS (GOGO) STUDY: STUDY DESIGN AND EVALUATION OF OSTEOARTHRITIS PHENOTYPES.

This large genetic study aimed to identify chromosomal regions linked to generalized osteoarthritis by recruiting 2,728 participants from 1,145 families where at least two siblings had clinical hand osteoarthritis. Researchers used radiographic imaging (X-rays) of hands, knees, hips, and spine to define osteoarthritis patterns, with the "gold standard" requiring specific hand joint involvement confirmed on X-rays.

The study identified distinct osteoarthritis phenotypes, finding that 73% of participants with clinical hand osteoarthritis also had radiographic confirmation, and among those with hand osteoarthritis, about half also had knee (51%) or spine (54%) involvement, while hip involvement was less common (25%). Importantly, 53% of affected sibling pairs showed similar patterns of multi-joint osteoarthritis, suggesting strong genetic clustering of specific osteoarthritis phenotypes.

These findings support the concept that generalized osteoarthritis represents distinct subgroups rather than a single condition, with different patterns of joint involvement that run in families. For physiotherapy and management, this suggests that treatment approaches may need to be tailored to specific multi-joint patterns, with practitioners assessing and addressing the broader pattern of joint involvement rather than treating individual joints in isolation.

FIVE TYPES OF INFLAMMATORY ARTHRITIS FOLLOWING TOTAL KNEE ARTHROPLASTY.

This study aimed to identify the different causes of joint swelling after total knee replacement surgery and examine the specific immune cell patterns in joint fluid for each cause. Researchers analyzed joint fluid from 95 patients (46 with rheumatoid arthritis, 49 with osteoarthritis) who developed swelling after knee replacement, using clinical assessment and specialized cell analysis techniques. They identified five distinct types of inflammation: deep infection, increased rheumatoid arthritis activity, particle-induced inflammation, metal sensitivity, and non-specific inflammation, with each type showing unique immune cell patterns (specific neutrophils, macrophages, or T-cells). These findings suggest that analyzing joint fluid cell types could help physiotherapists and clinicians better identify the underlying cause of post-surgical swelling, leading to more targeted treatment approaches rather than generic anti-inflammatory management.

PHENOTYPING OF CHONDROCYTES IN VIVO AND IN VITRO USING CDNA ARRAY TECHNOLOGY.

This study aimed to use advanced gene analysis technology (cDNA arrays) to identify and classify different types of cartilage cells (chondrocytes) in both living tissue and laboratory conditions. The researchers analyzed gene expression patterns in healthy and osteoarthritic cartilage samples using clustering algorithms to group cells with similar genetic profiles. The analysis successfully distinguished between cartilage cells in their natural environment versus laboratory cultures in 100% of cases, and could also differentiate between healthy and diseased cartilage based on their unique genetic signatures. These findings suggest that genetic profiling could potentially be developed into diagnostic tools for identifying osteoarthritis subtypes and disease progression, which may help physiotherapists and clinicians tailor more personalized treatment approaches based on the specific biological characteristics of a patient's cartilage.

GLUCOSAMINE PROMOTES CHONDROGENIC PHENOTYPE IN BOTH CHONDROCYTES AND MESENCHYMAL STEM CELLS AND INHIBITS MMP-13 EXPRESSION AND MATRIX DEGRADATION.

This study investigated whether glucosamine (a supplement commonly used for joint health) can promote cartilage-forming properties in both cartilage cells and stem cells, and protect against cartilage breakdown. The researchers used laboratory cell cultures to test different doses of glucosamine on human mesenchymal stem cells and cartilage cells from both healthy and arthritic joints, measuring cartilage-related gene expression and matrix production.

The study found that moderate doses of glucosamine (100 micromolar) enhanced the cells' ability to produce key cartilage components like collagen II and aggrecan, while also reducing the production of MMP-13, an enzyme that breaks down cartilage matrix - however, very high doses were actually harmful. Importantly, glucosamine showed similar beneficial effects in both normal and osteoarthritic cartilage cells, and helped counteract the damaging effects of inflammatory signals.

These findings suggest that glucosamine supplements may support cartilage health by promoting cartilage formation and reducing cartilage breakdown, potentially explaining why some patients with osteoarthritis report benefits from glucosamine supplementation as part of their management strategy.

INFLAMMATORY RESPONSE IN PATIENTS UNDERGOING HIP SURGERY DUE TO OSTEOARTHROSIS OR DIFFERENT TYPES OF HIP FRACTURES.

This study aimed to compare inflammatory responses in patients undergoing different types of hip surgery - elective hip replacement for osteoarthritis versus surgery for intracapsular (IC) or extracapsular (EC) hip fractures. Researchers measured various inflammatory markers and adhesion molecules in 65 patients before surgery and at multiple time points afterward (4 hours, 48 hours, and 7 days post-surgery).

The study identified three distinct inflammatory phenotypes: patients with intracapsular fractures showed the highest pre-surgical inflammation levels and slowest recovery, extracapsular fracture patients had intermediate responses, while elective surgery patients had the lowest baseline inflammation but still experienced significant post-surgical increases. An unexpected finding was that certain adhesion molecules (selectins) actually decreased after surgery in all groups, contrary to typical inflammatory patterns.

These findings suggest that hip fracture patients, particularly those with intracapsular fractures, may need more intensive anti-inflammatory management and potentially longer rehabilitation periods due to their prolonged inflammatory response, which could impact healing and recovery outcomes.

JOINT MODELLING OF MIXED OUTCOME TYPES USING LATENT VARIABLES.

This study aimed to develop and evaluate statistical methods for analyzing multiple different types of health outcomes together using latent (hidden) variables, with a specific application to osteoarthritis research. The researchers used theoretical calculations, computer simulations, and real osteoarthritis data to test how well these joint modeling approaches work compared to analyzing outcomes separately. The key finding was that joint models using latent variables provided more accurate and efficient results when analyzing mixed outcome types (such as combining pain scores, physical function measures, and imaging data) compared to traditional separate analyses. For osteoarthritis management and physiotherapy, this statistical approach could help identify distinct patient subgroups and phenotypes by better capturing the complex relationships between different symptoms and functional measures, potentially leading to more personalized treatment strategies.

SRC KINASE INHIBITION PROMOTES THE CHONDROCYTE PHENOTYPE.

This study investigated whether blocking SRC kinase proteins could help maintain healthy cartilage cell characteristics, which is important for understanding cartilage development and diseases like osteoarthritis. Researchers used mouse cartilage cells in laboratory cultures and treated them with a drug called PP2 that blocks SRC kinase activity, then measured changes in cell behavior and gene expression. They found that blocking SRC kinases promoted the cells to maintain their proper cartilage-producing characteristics - the cells became more rounded (their natural shape), produced more cartilage-specific proteins, and showed better markers of healthy cartilage cell function. These findings suggest that SRC kinase inhibitors could potentially be used in cartilage tissue engineering or as treatments to help preserve healthy cartilage cells in osteoarthritis, though this research was conducted in laboratory settings and would need further testing before clinical application.

ACQUISITION, CULTURE, AND PHENOTYPING OF SYNOVIAL FIBROBLASTS.

This methodological study aimed to establish standardized procedures for isolating, culturing, and characterizing fibroblast-like synoviocytes (FLS) from joint tissue to better understand rheumatoid arthritis disease mechanisms. The researchers used collagenase digestion to extract cells from synovial tissue obtained during joint surgeries or biopsies, then cultured and passaged the cells to enrich for synovial fibroblasts while eliminating other cell types like macrophages. They found that FLS develop a distinct phenotype in culture, expressing specific surface markers (VCAM-1, CD44, CD55, CD90, and cadherin-11) while lacking macrophage markers, and maintain their characteristics reliably through passage 3-9. This standardized approach for identifying and studying synovial fibroblast subpopulations could help researchers better understand different arthritis phenotypes and potentially lead to more targeted treatments, though direct physiotherapy applications are not immediately apparent from this technical methodology paper.

TRANSFORMING GROWTH FACTOR ALPHA SUPPRESSION OF ARTICULAR CHONDROCYTE PHENOTYPE AND SOX9 EXPRESSION IN A RAT MODEL OF OSTEOARTHRITIS.

This study investigated how transforming growth factor alpha (TGFα) contributes to cartilage breakdown in osteoarthritis using rat cartilage cells and tissue samples. The researchers cultured cartilage cells with TGFα and analyzed gene expression in cartilage samples from 13 healthy individuals and 12 people with severe knee osteoarthritis.

The key finding was that TGFα caused harmful changes to cartilage cells, reducing production of healthy cartilage components while increasing enzymes that break down cartilage. Importantly, the study identified distinct osteoarthritis phenotypes - about 40% of patients with severe osteoarthritis showed markedly elevated TGFα levels, while the remaining 60% had normal levels similar to healthy controls.

These findings suggest that osteoarthritis patients with high TGFα levels may represent a specific subgroup requiring targeted treatments, and TGFα could be a potential therapeutic target for developing personalized osteoarthritis management strategies.

THE HUNTER-MACDONALD SYNDROME WITH EXPANDED PHENOTYPE INCLUDING RISK OF MENINGIOMA: AN UPDATE AND REVIEW.

This study aimed to expand understanding of Hunter-MacDonald Syndrome (HMS) phenotypes by reviewing clinical manifestations in affected families and presenting two new cases. The researchers used case reports and family pedigree analysis to document the range of symptoms across multiple body systems. Key findings revealed that HMS presents with a consistent phenotype including early-onset osteoarthritis requiring joint replacement, spinal deformities (scoliosis), limb malformations, and notably an increased risk of brain tumors (meningiomas) which the authors now consider a major feature of the condition. For physiotherapy management, these findings suggest patients with HMS require specialized care focusing on early joint preservation strategies, scoliosis monitoring, and comprehensive musculoskeletal assessment, while being aware that neurological symptoms may indicate serious complications requiring immediate medical attention.

THE POTENTIAL OF N-RICH PLASMA-POLYMERIZED ETHYLENE (PPE:N) FILMS FOR REGULATING THE PHENOTYPE OF THE NUCLEUS PULPOSUS.

This study investigated whether a nitrogen-rich biomaterial (PPE:N) could help maintain the specialized cell characteristics of nucleus pulposus (NP) cells - the gel-like center of spinal discs that deteriorates in disc degeneration. The researchers cultured fetal bovine NP cells on surfaces with different nitrogen concentrations and measured the expression of genes that are markers of healthy NP tissue phenotype. They found that nitrogen concentration affected the expression of several NP-specific genes (GPC3, VIM, PTN, and MGP), with some genes decreasing as nitrogen levels decreased, while structural proteins like collagen and aggrecan remained unchanged. These findings suggest that PPE:N biomaterials could potentially serve as scaffolds for growing or maintaining healthy disc cells, which may have future applications in developing treatments for disc degeneration and back pain, though more research is needed to fully understand these cellular responses.

PHENOTYPIC CHARACTERIZATION OF OSTEOBLASTS FROM THE SCLEROTIC ZONES OF OSTEOARTHRITIC SUBCHONDRAL BONE.

This study aimed to characterize the specific traits of bone-forming cells (osteoblasts) found in hardened, sclerotic areas of bone beneath damaged cartilage in people with osteoarthritis. Researchers isolated osteoblasts from both sclerotic and normal areas of subchondral bone, cultured them for 14 days, and compared their gene expression, enzyme activities, and protein production using various molecular techniques.

The findings revealed that osteoblasts from sclerotic zones had a distinctly altered phenotype, showing increased expression of genes involved in bone formation, blood vessel growth, and inflammation, along with higher production of inflammatory proteins and bone markers. Paradoxically, despite this increased activity, these cells showed reduced ability to form mineralized bone tissue compared to osteoblasts from normal areas.

These results suggest that targeting the abnormal behavior of osteoblasts in sclerotic subchondral bone could be a new therapeutic approach for osteoarthritis, potentially informing future treatments that address both the cartilage damage and underlying bone changes that characterize this condition.

BIOMARKERS ASSOCIATED WITH CLINICAL PHENOTYPES OF HAND OSTEOARTHRITIS IN A LARGE MULTIGENERATIONAL FAMILY: THE CARRIAGE FAMILY STUDY.

This study aimed to identify biological markers that could serve as measurable traits for different clinical forms of hand osteoarthritis (OA) by examining a large family group over 6 years. Researchers assessed 287 family members using physical hand examinations and measured seven blood markers related to cartilage breakdown and inflammation, comparing those with hand OA to those without OA or with joint symptoms but no clinical OA.

The study identified distinct biomarker patterns for different hand OA phenotypes: people with clinical hand OA had higher levels of inflammatory markers (HA, COMP, hs-CRP) but lower levels of a cartilage repair marker (PIIANP), while those with joint symptoms but no clinical OA showed elevated blood sugar-related protein (GSP). This suggests that hand OA involves reduced cartilage repair capacity alongside increased inflammation, and that people with early symptoms may have different underlying biological processes.

These findings could help physiotherapists and clinicians identify patients at different stages of hand OA development and tailor treatments accordingly - for example, focusing on anti-inflammatory approaches for those with established OA versus preventive strategies for those with early symptoms but different biomarker profiles.

CHONDROCYTES HARVESTED FROM OSTEOCHONDRITIS DISSECANS CARTILAGE ARE ABLE TO UNDERGO LIMITED IN VITRO CHONDROGENESIS DESPITE HAVING PERTURBATIONS OF CELL PHENOTYPE IN VIVO.

This study aimed to compare the genetic characteristics of cartilage cells from osteochondritis dissecans (OCD) lesions versus normal cartilage, and test whether OCD cells could be "reprogrammed" to behave more normally under laboratory conditions. Researchers collected cartilage samples from horses with OCD during surgery and compared gene expression patterns to normal samples, then cultured both cell types under conditions designed to promote healthy cartilage formation.

The findings revealed that OCD cartilage cells had significantly altered gene expression patterns, producing more inflammatory enzymes and different types of collagen compared to normal cells, indicating a disrupted cellular phenotype. When cultured under optimal laboratory conditions, OCD cells showed some ability to form cartilage-like tissue, but their performance remained inferior to normal cells, producing less cartilage matrix and maintaining some abnormal characteristics.

These results suggest that while cartilage cells from OCD lesions retain some regenerative potential, they have fundamental defects that may limit the success of cell-based therapies, highlighting the importance of early intervention and the need for rehabilitation strategies that account for the altered biology of damaged cartilage.

INDUCTION OF CHONDROGENIC PHENOTYPE IN SYNOVIUM-DERIVED PROGENITOR CELLS BY INTERMITTENT HYDROSTATIC PRESSURE.

This laboratory study investigated whether intermittent hydrostatic pressure (IHP) - a type of mechanical loading - could stimulate synovium-derived progenitor cells to develop cartilage-like characteristics. Researchers exposed rabbit cells to different pressure levels (1.0-5.0 MPa) and measured the production of cartilage markers like collagen type II and proteoglycans using molecular biology techniques. The key finding was that only the highest pressure (5.0 MPa) successfully induced synovium cells to produce cartilage-building proteins, while lower pressures and other cell types showed no response. These results suggest that specific high-intensity mechanical loading protocols could potentially be developed as physiotherapy interventions to promote cartilage repair in osteoarthritis, though translation from laboratory to clinical practice would require further research on safe and effective pressure application methods.

EXPANDED HSAN4 PHENOTYPE ASSOCIATED WITH TWO NOVEL MUTATIONS IN NTRK1.

This study aimed to describe a rare, mild form of Hereditary Sensory and Autonomic Neuropathy Type IV (HSAN4) caused by two newly discovered genetic mutations. The researchers conducted a detailed clinical assessment of a Swedish patient with novel mutations in the NTRK1 gene. They identified an expanded, milder phenotype of HSAN4 that begins in adulthood rather than childhood, featuring painful joint destruction (Charcot arthropathy), slow wound healing, and reduced sweating, but without the typical severe complications like cognitive impairment or aggressive behavior. This finding suggests that HSAN4 can present as a milder adult-onset condition, which has important implications for diagnosis and may require different management approaches, including careful monitoring for joint problems and wound care in physiotherapy treatment.

MAGNITUDE AND MEANINGFULNESS OF CHANGE IN SF-36 SCORES IN FOUR TYPES OF ORTHOPEDIC SURGERY.

This study examined how well the SF-36 health questionnaire captures meaningful changes after four types of orthopedic surgeries: total hip replacement, total knee replacement, arthroscopic meniscectomy, and ACL reconstruction. The researchers analyzed data from 494 patients across these surgery types, measuring changes in physical, mental, and social health domains at various follow-up periods (3 months to 5 years).

The study found that different surgical procedures showed distinct patterns of improvement, with all surgeries producing large improvements in physical function and pain, but smaller gains in mental and social aspects - though patients with joint replacements still remained below normal population levels for physical function even years after surgery.

Importantly, while the SF-36 effectively measured group-level changes, it had poor sensitivity for tracking individual patient progress due to ceiling and floor effects. For physiotherapy practice, this suggests the SF-36 is useful for comparing treatment outcomes across patient groups or research studies, but clinicians should use more sensitive, condition-specific measures when monitoring individual patient recovery and tailoring rehabilitation programs.

ACTIVATION OF BETA-CATENIN SIGNALING IN ARTICULAR CHONDROCYTES LEADS TO OSTEOARTHRITIS-LIKE PHENOTYPE IN ADULT BETA-CATENIN CONDITIONAL ACTIVATION MICE.

This study aimed to investigate whether beta-catenin signaling activation in joint cartilage cells directly causes osteoarthritis (OA) development. Researchers used genetically modified mice where beta-catenin could be activated specifically in cartilage cells of adult animals, then examined joint changes over time and compared findings to human OA samples.

The study identified a clear OA-like disease pattern: younger mice (5 months) showed early cartilage damage and loss, while older mice (8 months) developed severe features including complete cartilage loss, bone changes, and bone spur formation - mimicking human OA progression. Key cartilage-degrading enzymes and bone-forming markers were significantly increased (3-6 fold), and similar beta-catenin overexpression was found in human OA joint samples.

These findings suggest that targeting beta-catenin signaling could be important for OA treatment, and the age-related progression pattern supports the concept that OA phenotypes may vary based on disease stage, potentially requiring different physiotherapy approaches for early versus advanced disease.

ASSOCIATION OF A NSSNP IN ADAMTS14 TO SOME OSTEOARTHRITIS PHENOTYPES.

This study aimed to investigate whether genetic variations in ADAM and ADAMTS protease genes increase susceptibility to osteoarthritis (OA). Researchers analyzed potentially damaging genetic variants in these genes across 3,217 OA patients and 2,214 healthy controls, all of Caucasian ethnicity, examining different OA phenotypes including knee, hip, and hand OA.

The key finding was that a rare genetic variant (rs4747096) in the ADAMTS14 gene was more common in women requiring knee joint replacement (41% increased risk) and patients with symptomatic hand OA (37% increased risk), but showed no association with other OA phenotypes. This suggests that ADAMTS14 genetic variation may contribute to specific, more severe forms of OA rather than affecting all joint types equally.

These findings highlight the importance of recognizing distinct OA phenotypes, particularly severe knee OA in women, which may have different underlying genetic mechanisms. For physiotherapy practice, this research supports the concept that OA patients may benefit from phenotype-specific treatment approaches, especially when managing severe knee OA in female patients who may have different underlying disease processes.

INDUCTION OF AN OSTEOARTHRITIS-LIKE PHENOTYPE AND DEGRADATION OF PHOSPHORYLATED SMAD3 BY SMURF2 IN TRANSGENIC MICE.

This study aimed to investigate whether SMURF2, a protein that blocks protective cartilage signaling, is involved in osteoarthritis development in both humans and mice. Researchers examined cartilage samples from patients undergoing knee replacement surgery and created genetically modified mice that overproduced SMURF2, then analyzed cartilage changes using various laboratory techniques.

The key findings showed that SMURF2 levels were much higher in human osteoarthritic cartilage compared to healthy cartilage, and mice with increased SMURF2 spontaneously developed osteoarthritis-like changes by 8 months of age, including cartilage breakdown, bone changes, and increased production of cartilage-destroying enzymes. This occurred through disruption of the TGF-beta signaling pathway, which normally protects cartilage from damage.

These findings suggest that SMURF2 plays an important role in osteoarthritis development and could represent a potential target for future treatments aimed at preserving cartilage and slowing disease progression, though this research is still in early laboratory stages before any clinical applications for physiotherapy or patient management.

SYNOVIAL B CELLS OF RHEUMATOID ARTHRITIS EXPRESS ZAP-70 WHICH INCREASES THE SURVIVAL AND CORRELATES WITH THE INFLAMMATORY AND AUTOIMMUNE PHENOTYPE.

This study aimed to investigate ZAP-70 as a biomarker of B cell immune activation in rheumatoid arthritis (RA) patients. Researchers analyzed B cells from synovial fluid and peripheral blood of RA and osteoarthritis patients, examining ZAP-70 expression, cell survival, and correlations with inflammatory markers and autoantibodies. The key finding was that RA patients had higher levels of ZAP-70-positive B cells in their joint fluid compared to osteoarthritis patients, and these ZAP-70-positive B cells showed increased survival and were associated with higher levels of autoantibodies and inflammatory markers (BAFF and IL-6). This identifies a specific B cell subgroup in RA that may be more resistant to cell death and more involved in driving joint inflammation, potentially offering a new target for personalized treatment approaches, particularly for patients who don't respond well to current anti-TNF therapies.

RELIABILITY OF CLUSTER RESULTS FOR DIFFERENT TYPES OF TIME ADJUSTMENTS IN COMPLEX DISEASE RESEARCH.

This study aimed to improve the reliability of identifying disease subtypes in osteoarthritis (OA) and Parkinson's disease (PD) by determining the best way to account for time-related changes in disease severity markers. The researchers tested different mathematical approaches to adjust for age effects in OA and disease duration effects in PD, then added varying levels of "noise" to the data to see which adjustments produced the most stable clustering results. They found that using a logarithmic adjustment for age in OA patients and a square root adjustment for disease duration in PD patients led to the most reliable identification of patient subgroups. These findings suggest that proper time adjustments are crucial for accurately identifying distinct disease phenotypes, which could help physiotherapists and clinicians better tailor treatments to specific patient subgroups rather than using one-size-fits-all approaches.

CHRONIC INCREASES IN SPHINGOSINE KINASE-1 ACTIVITY INDUCE A PRO-INFLAMMATORY, PRO-ANGIOGENIC PHENOTYPE IN ENDOTHELIAL CELLS.

This study investigated how increased levels of sphingosine kinase-1 (SK1), an enzyme that promotes inflammation and blood vessel formation, affects endothelial cells (cells lining blood vessels) and whether this pathway is involved in rheumatoid arthritis. Researchers genetically modified human endothelial cells to produce 3-5 times more SK1 and tested their inflammatory and blood vessel-forming properties, while also measuring SK1's product (S1P) in joint fluid from rheumatoid arthritis (RA) and osteoarthritis (OA) patients. The modified cells showed enhanced ability to migrate, form new blood vessels, and bind inflammatory cells, plus they were more sensitive to inflammatory signals compared to normal cells; additionally, RA patients had significantly higher S1P levels in their joint fluid than OA patients. These findings suggest that RA and OA represent distinct inflammatory phenotypes, with RA characterized by enhanced blood vessel formation and inflammation through the SK1 pathway, potentially offering new targets for personalized treatment approaches that could complement physiotherapy by addressing the underlying vascular and inflammatory differences between these conditions.

CONFIRMATION OF TWO MAJOR POLYARTICULAR OSTEOARTHRITIS (POA) PHENOTYPES--DIFFERENTIATION ON THE BASIS OF JOINT TOPOGRAPHY.

This study aimed to validate two proposed types of polyarticular osteoarthritis (POA) based on which hand joints are affected first and their clinical characteristics. Researchers examined X-rays and genetic markers in 67 patients, classifying them as Type 1 POA (affecting finger joints like DIP/PIP) or Type 2 POA (affecting knuckle joints like MCP2,3), and tested for haemochromatosis gene mutations.

The study confirmed two distinct phenotypes: Type 1 POA was more common in women (85%) and typically presented with Heberden's nodes, resembling classic generalized osteoarthritis, while Type 2 POA was more common in men (64%) and strongly associated with haemochromatosis gene mutations (75% vs 23% in Type 1).

These findings suggest that osteoarthritis patients can be meaningfully grouped into subgroups based on joint involvement patterns and underlying genetic factors, with Type 2 POA sharing characteristics with haemochromatosis-related joint disease. For physiotherapy practice, this phenotyping approach could help tailor treatment strategies based on the specific joint involvement patterns and underlying mechanisms, potentially leading to more personalized rehabilitation programs for different osteoarthritis subgroups.

EXTENDED APPLICATION OF WISH TYPE S-FORM HIP BRACE FOR PATIENTS WITH BILATERAL PAINFUL HIP OSTEOARTHRITIS: REPORT OF TWO CASES.

This study aimed to evaluate an extended version of the WISH-type hip brace for patients with painful osteoarthritis affecting both hips. The researchers modified their existing single-hip brace design to include two S-form portions that could stabilize both hips simultaneously, and tested it on two patients with bilateral hip OA, using measures like the Timed Up & Go test to assess functional mobility.

The key finding was that patients with bilateral hip osteoarthritis represent a distinct subgroup that responds poorly to single-hip bracing but shows improved hip function and mobility when both hips are supported simultaneously. The bilateral brace design provided better functional recovery compared to the original single-hip version for this specific patient phenotype.

These results suggest that bilateral hip OA patients may require different management approaches than those with single-hip involvement, and that bilateral bracing could serve as a non-surgical treatment option. For physiotherapy practice, this highlights the importance of considering bilateral stabilization strategies before recommending invasive procedures like total hip replacement for patients with painful OA in both hips.

NEUTROPHILS EXHIBIT DISTINCT PHENOTYPES TOWARD CHITOSANS WITH DIFFERENT DEGREES OF DEACETYLATION: IMPLICATIONS FOR CARTILAGE REPAIR.

This study investigated how different types of chitosan (a biomaterial used in cartilage repair) affect neutrophil immune cells, since chitosan with 80% deacetylation has shown promise in promoting cartilage regeneration after microfracture surgery. Researchers compared the effects of 80% versus 95% deacetylated chitosan on isolated human neutrophils using various laboratory assays to measure cell attraction, activation, and uptake of the materials. The key finding was that neutrophils showed distinct responses to the two chitosan types - 80% deacetylated chitosan attracted neutrophils without causing harmful inflammatory activation, while 95% deacetylated chitosan did not attract neutrophils at all, suggesting different therapeutic potential. These results indicate that the specific degree of chitosan deacetylation is crucial for optimizing cartilage repair therapies, and that 80% deacetylated chitosan may promote healing by recruiting neutrophils in a controlled, non-inflammatory manner.

CHARACTERIZATION OF HUMAN MESENCHYMAL STEM CELL-ENGINEERED CARTILAGE: ANALYSIS OF ITS ULTRASTRUCTURE, CELL DENSITY AND CHONDROCYTE PHENOTYPE COMPARED TO NATIVE ADULT AND FETAL CARTILAGE.

This study aimed to characterize cartilage tissue engineered from human mesenchymal stem cells (hMSCs) by comparing it to natural adult and fetal cartilage. Researchers grew hMSCs in laboratory conditions for 3 weeks and then analyzed the resulting cartilage using various microscopy techniques and measurements of cell density and tissue structure. The engineered cartilage showed similar cell types, structural proteins, and tissue organization to natural cartilage, with cell density falling between adult and fetal levels - specifically matching fetal cartilage in terms of cell-to-tissue ratios. These findings suggest that stem cell-engineered cartilage could potentially be used to repair damaged joints in conditions like osteoarthritis, offering a regenerative approach that mimics how cartilage naturally develops, which may inform future cartilage repair treatments and rehabilitation strategies.

C-REACTIVE PROTEIN LEVELS AFTER 4 TYPES OF ARTHROPLASTY.

This study aimed to compare inflammatory responses (measured by C-reactive protein levels) across four different types of joint replacement surgeries to understand how surgical trauma varies between procedures. The researchers measured CRP levels before surgery and at 2 and 7 days after surgery in 102 patients undergoing total knee arthroplasty, computer-assisted knee arthroplasty, hip resurfacing, and total hip arthroplasty. The findings revealed that less invasive surgical techniques (computer-assisted knee surgery and hip resurfacing) produced lower peak inflammatory responses compared to conventional procedures, with bone and bone marrow damage being the key factor driving inflammation rather than soft tissue injury. These results suggest that surgical technique selection could influence recovery patterns, potentially informing physiotherapy approaches where patients undergoing less invasive procedures might be expected to have faster initial recovery phases due to reduced surgical trauma.

INTERLEUKIN-1 REGION META-ANALYSIS WITH OSTEOARTHRITIS PHENOTYPES.

This study aimed to clarify conflicting research about whether genetic variations in the interleukin-1 (IL-1) region are linked to different types of osteoarthritis by combining data from multiple research centers. The researchers used meta-analysis methods to analyze genetic data from over 2,500 people of European descent, examining specific genetic patterns (haplotypes) associated with hand, knee, and hip osteoarthritis across four study centers. The findings showed that IL-1 genetic variants may have a modest protective effect against hand osteoarthritis, no clear association with knee osteoarthritis, and inconsistent results for hip osteoarthritis depending on how control groups were selected. These results suggest that genetic factors related to inflammation may influence osteoarthritis differently depending on which joints are affected, potentially informing future personalized treatment approaches and helping physiotherapists understand that osteoarthritis may require joint-specific management strategies.

CHANGES IN CONTENT AND SYNTHESIS OF COLLAGEN TYPES AND PROTEOGLYCANS IN OSTEOARTHRITIS OF THE KNEE JOINT AND COMPARISON OF QUANTITATIVE ANALYSIS WITH PHOTOSHOP-BASED IMAGE ANALYSIS.

This study aimed to analyze changes in cartilage composition during knee osteoarthritis and compare two methods for detecting these changes: molecular analysis (RT-PCR) and a novel Photoshop-based image analysis technique. Researchers examined cartilage samples from 20 osteoarthritis patients and 20 healthy controls using immunohistochemistry, RT-PCR, and digital image analysis to measure collagen types I and II, and proteoglycans.

The study found that osteoarthritic cartilage shows a pathological shift from healthy collagen type II to collagen type I, with this change being most pronounced in advanced disease stages and the upper damaged cartilage layers. Additionally, proteoglycan content decreased overall and lost its normal organized zonal distribution pattern in diseased cartilage.

The Photoshop-based image analysis showed strong correlation with molecular methods for some markers, suggesting it could serve as a valuable supplementary tool for grading cartilage damage. This research supports the concept of osteoarthritis phenotyping based on cartilage composition changes and suggests that digital image analysis could provide clinicians with a more accessible method for assessing cartilage quality, potentially informing treatment decisions and monitoring disease progression in physiotherapy and rehabilitation settings.

PHENOTYPIC CHARACTERIZATION OF EPIPHYCAN-DEFICIENT AND EPIPHYCAN/BIGLYCAN DOUBLE-DEFICIENT MICE.

This study aimed to understand how epiphycan (EPN), a protein involved in cartilage structure, affects joint health by examining genetically modified mice lacking this protein alone or in combination with another protein called biglycan. Researchers created mice with specific gene deletions and analyzed their joint tissues using microscopic examination and gene expression studies over time. The findings revealed distinct phenotypes: mice lacking both proteins developed osteoarthritis earliest and most severely, followed by those missing only EPN, suggesting these proteins work together to protect joints from degeneration. These results indicate that identifying patients with genetic variations affecting these cartilage proteins could help predict osteoarthritis risk and guide early intervention strategies, potentially informing personalized physiotherapy approaches that focus on joint protection before significant cartilage damage occurs.

EXPRESSION OF COLLAGEN TYPES I AND II ON ARTICULAR CARTILAGE IN A RAT KNEE CONTRACTURE MODEL.

This study aimed to understand how immobilization affects collagen expression in different areas of knee joint cartilage using a rat model of knee contracture. Researchers immobilized rat knees at 150 degrees of flexion and analyzed collagen types I and II expression in three distinct cartilage regions (noncontact, transitional, and contact areas) using multiple laboratory techniques including genetic analysis and tissue staining.

The study revealed that cartilage responded differently to immobilization depending on the specific region examined - collagen type II (the "good" cartilage collagen) decreased in areas not experiencing joint contact, while collagen type I (associated with inferior cartilage quality) increased in noncontact and transitional areas. These findings suggest that immobilization creates distinct patterns of cartilage degeneration, with different areas of the joint developing different types of structural problems.

For physiotherapy and rehabilitation, this research highlights the importance of early mobilization to prevent cartilage deterioration, and suggests that different areas of an immobilized joint may require targeted treatment approaches since they develop distinct degenerative patterns.

PREMATURE ARTHRITIS IS A DISTINCT TYPE II COLLAGEN PHENOTYPE.

This study aimed to identify genetic causes of premature arthritis by examining families with early-onset degenerative joint disease. The researchers analyzed the COL2A1 gene (which produces type II collagen) in two Australian families where multiple members developed arthritis in both large and small joints before age 30, and found specific genetic mutations in both families. The key finding was that these COL2A1 mutations can cause isolated early arthritis without the typical features usually seen with collagen disorders (like short stature, eye problems, or hearing loss), representing a distinct disease subgroup. This genetic identification is important for physiotherapy and management because it allows early identification of at-risk family members who can then benefit from preventive strategies such as weight management and joint-protective exercise programs before symptoms develop.

LOCAL LEPTIN PRODUCTION IN OSTEOARTHRITIS SUBCHONDRAL OSTEOBLASTS MAY BE RESPONSIBLE FOR THEIR ABNORMAL PHENOTYPIC EXPRESSION.

This study investigated whether leptin (a hormone involved in bone metabolism) produced by bone cells called osteoblasts contributes to abnormal bone changes in osteoarthritis (OA). The researchers compared osteoblasts from normal and OA knee bone tissue, measuring leptin production and testing how blocking leptin affected various cellular functions and biomarkers. They found that OA osteoblasts produced significantly more leptin than normal cells, and this excess leptin appeared to drive the abnormal characteristics of OA bone cells - when leptin was blocked, the abnormal biomarker levels were reduced by about 60%. These findings suggest that OA may involve distinct bone cell phenotypes driven by local leptin overproduction, which could potentially be targeted with therapies aimed at reducing leptin signaling to help normalize bone metabolism in OA patients.

IDENTIFYING DIFFERENT OSTEOARTHRITIS PHENOTYPES THROUGH EPIDEMIOLOGY.

I notice that the abstract is listed as "NA" (not available), which makes it impossible to provide a meaningful summary of the study's methods, findings, and implications.

Based solely on the title "Identifying Different Osteoarthritis Phenotypes Through Epidemiology," I can only infer that this study likely aimed to use population-based epidemiological approaches to classify different subtypes or patterns of osteoarthritis. However, without access to the abstract or full paper, I cannot provide details about the specific methods used, what phenotypes were identified, or what this means for patient management and physiotherapy practice.

To write the comprehensive 3-4 sentence summary you've requested covering the study objective, methods, findings, and clinical implications, I would need access to the actual abstract or study details.

CHARACTERISTICS OF SUBJECTS SELF-REPORTING ARTHRITIS IN A POPULATION HEALTH SURVEY: DISTINGUISHING BETWEEN TYPES OF ARTHRITIS.

This study aimed to determine whether people with different types of arthritis could be reliably distinguished in population health surveys based on their self-reported characteristics. Researchers analyzed data from nearly 120,000 Canadian adults who reported having osteoarthritis, rheumatoid arthritis, or other types of arthritis, comparing them across 34 variables including demographics, lifestyle, health conditions, medication use, and physical function. The key finding was that people reporting different arthritis types showed very few distinguishing characteristics, with only age and gender differences noted (osteoarthritis patients were older and more likely to be female). This suggests that current population surveys cannot reliably separate arthritis subtypes, limiting their usefulness for developing targeted management strategies, and highlighting the need for better survey questions to properly identify distinct arthritis phenotypes for more personalized physiotherapy and treatment approaches.

CHANGES IN CHONDROGENIC PHENOTYPE AND GENE EXPRESSION PROFILES ASSOCIATED WITH THE IN VITRO EXPANSION OF HUMAN SYNOVIUM-DERIVED CELLS.

This study aimed to understand how human synovium-derived stem cells from osteoarthritis patients change when grown in laboratory conditions over multiple passages. The researchers cultured these cells for up to 130 days, tracking their growth rates, surface markers, ability to form cartilage, and gene expression patterns at different time points. Key findings showed that cells from osteoarthritis patients could be successfully expanded, but after passage 6, they showed declining growth rates and significantly reduced ability to produce cartilage components (type II collagen and glycosaminoglycans), with gene expression shifting toward patterns associated with cellular aging. These results suggest that for potential cartilage repair therapies using synovium-derived cells, earlier passage cells (before passage 6) would likely be more effective, as they retain better cartilage-forming capabilities before age-related decline sets in.

PREVALENCE OF SPECIFIC TYPES OF ARTHRITIS AND OTHER RHEUMATIC CONDITIONS IN THE AMBULATORY HEALTH CARE SYSTEM IN THE UNITED STATES, 2001-2005.

This study aimed to estimate the prevalence of medically-treated arthritis and other rheumatic conditions (AORC) among US adults and determine healthcare utilization patterns. The researchers analyzed data from national ambulatory care surveys (2001-2005) and converted healthcare visit data into prevalence estimates using information about visit frequency per condition.

The study found that approximately 29.2 million US adults received medical treatment for AORC, generating nearly 78 million ambulatory care visits annually. The five most prevalent conditions were osteoarthritis and allied disorders, unspecified joint disorders, peripheral enthesopathies, unspecified arthropathies, and other synovium/tendon/bursa disorders.

These findings highlight the substantial healthcare burden of musculoskeletal conditions and suggest that physiotherapy services need to be prepared to manage a diverse range of arthritis phenotypes, with osteoarthritis being the most common condition requiring ongoing ambulatory care management.

RACIAL AND ETHNIC DISPARITIES IN OSTEOARTHRITIS PHENOTYPES.

This paper aimed to summarize existing research on how osteoarthritis varies across different racial and ethnic groups. The authors reviewed previous studies examining differences in disease prevalence, X-ray features, and pain/function levels between racial groups. Key findings revealed distinct osteoarthritis patterns by race and joint location: knee osteoarthritis was more common in African-Americans and Chinese women compared to Caucasians, while hip and hand osteoarthritis were less common in Chinese individuals, and African-Americans experienced greater pain and disability from knee osteoarthritis than Caucasians. These findings suggest that physiotherapy and rehabilitation approaches may need to be tailored by racial group, particularly emphasizing weight management and psychological support interventions for African-American patients with knee osteoarthritis.

STICKLER SYNDROME AND THE VITREOUS PHENOTYPE: MUTATIONS IN COL2A1 AND COL11A1.

This study aimed to identify genetic mutations causing Stickler syndrome and correlate them with specific eye abnormalities (vitreous phenotypes) to improve disease classification. The researchers analyzed 89 families with Stickler syndrome, identifying 57 new genetic mutations in the COL2A1 and COL11A1 genes and examining how these mutations affected the eye's vitreous structure. They found that different genetic mutations produce distinct vitreous phenotypes: COL2A1 mutations typically cause membranous vitreous abnormalities, COL11A1 mutations create irregular, beaded patterns, and a newly identified COL2A1 subgroup results in underdeveloped vitreous with sparse structures. These findings are important for physiotherapy and management because they help predict which patients are likely to develop premature osteoarthritis and other joint problems, allowing for earlier intervention and more targeted treatment approaches.

ALTERATIONS IN OSTEOCLAST FUNCTION AND PHENOTYPE INDUCED BY DIFFERENT INHIBITORS OF BONE RESORPTION--IMPLICATIONS FOR OSTEOCLAST QUALITY.

This study aimed to investigate how different types of bone resorption inhibitors affect osteoclast function and create distinct cellular phenotypes. Researchers treated human osteoclasts (bone-dissolving cells) with various inhibitors targeting acidification, protein breakdown, or bisphosphonate pathways, then measured their ability to break down organic and inorganic bone components.

The study found that different inhibitor types created markedly different osteoclast phenotypes: acidification inhibitors blocked both organic and inorganic bone breakdown equally, protein breakdown inhibitors primarily affected organic resorption, while bisphosphonates completely stopped all resorption activity. These findings suggest that the specific mechanism of inhibiting osteoclasts matters significantly, as each approach creates osteoclasts with different functional capabilities.

For musculoskeletal conditions like osteoarthritis and osteoporosis, this research implies that treatment selection should consider not just whether bone breakdown is reduced, but how the quality and function of remaining osteoclasts is altered, potentially leading to more targeted therapeutic approaches in physiotherapy and bone health management.

RECESSIVE MULTIPLE EPIPHYSEAL DYSPLASIA (RMED) WITH HOMOZYGOSITY FOR C653S MUTATION IN THE DTDST GENE--PHENOTYPE, MOLECULAR DIAGNOSIS AND SURGICAL TREATMENT OF HABITUAL DISLOCATION OF MULTILAYERED PATELLA: CASE REPORT.

This case report aimed to describe the clinical features, genetic diagnosis, and surgical treatment of a rare form of multiple epiphyseal dysplasia (MED) in a 27-year-old man. The researchers used clinical examination, imaging, genetic testing, and surgical intervention to characterize this specific subtype of skeletal disorder caused by a particular gene mutation (C653S in the DTDST gene).

The key finding was that this genetic variant causes a relatively mild form of MED compared to other mutations in the same gene, with the main problems being joint pain, instability, and unusual kneecap dislocation due to abnormally shaped bone structures. The surgical treatment (moving the attachment point of the kneecap tendon) successfully resolved the kneecap dislocation problem, demonstrating that even complex joint abnormalities in this rare condition can be effectively managed with appropriate orthopedic surgery.

This highlights the importance of genetic testing to identify specific subtypes of joint disorders, as this information helps predict outcomes and guides treatment decisions for both patients and their families.

THE HISTOLOGICAL FEATURES OF ANTEROMEDIAL GONARTHROSIS--THE COMPARISON OF TWO GRADING SYSTEMS IN A HUMAN PHENOTYPE OF OSTEOARTHRITIS.

This study aimed to characterize the histological features of anteromedial gonarthrosis (AMG), a specific pattern of knee osteoarthritis affecting the inner part of the knee joint. Researchers examined cartilage samples from 16 patients at five different regions from front to back of the knee, using two different microscopic grading systems (Modified Mankin and OOCHAS) to assess cartilage quality.

The findings confirmed that AMG represents a clear progression of cartilage damage from front to back - severe damage with exposed bone at the front, moderate damage in the middle, and normal healthy cartilage at the back of the knee. Both grading systems effectively captured this pattern, though the OOCHAS system was found to be quicker and easier to use.

These results suggest that AMG represents a distinct osteoarthritis phenotype with predictable spatial patterns of cartilage loss, which could help clinicians better understand disease progression and potentially guide more targeted treatment approaches, including surgical planning and rehabilitation strategies focused on protecting the remaining healthy cartilage.

ISOLATION OF ADIPOSE-DERIVED STEM CELLS AND THEIR INDUCTION TO A CHONDROGENIC PHENOTYPE.

This study aimed to develop a protocol for isolating adipose-derived stem cells (ASCs) from liposuction material and converting them into cartilage-like cells for potential osteoarthritis treatment. The researchers used growth factors to transform ASCs into chondrocyte-like cells using two different culture methods (cell pellets and alginate beads), with the complete process taking 10-12 weeks. The study successfully demonstrated consistent differentiation of ASCs into cartilage-producing cells, though results varied somewhat depending on the donor and culture conditions. This research has important implications for developing regenerative therapies for joint cartilage repair in osteoarthritis patients, potentially offering a more accessible alternative to bone marrow-derived stem cells for future tissue engineering treatments that could complement traditional physiotherapy approaches.

INDUCTION OF HYPERTROPHIC CHONDROCYTE-LIKE PHENOTYPES BY OXIDIZED LDL IN CULTURED BOVINE ARTICULAR CHONDROCYTES THROUGH INCREASE IN OXIDATIVE STRESS.

This study investigated whether oxidized low-density lipoprotein (ox-LDL) - a harmful form of cholesterol - can trigger abnormal changes in cartilage cells that contribute to osteoarthritis development. Researchers exposed bovine cartilage cells to ox-LDL in laboratory conditions and measured changes in specific proteins (Type X collagen and RUNX2) that indicate cells are becoming "hypertrophic" - an abnormal, enlarged state associated with cartilage breakdown. The results showed that ox-LDL caused cartilage cells to develop this harmful hypertrophic phenotype through increased oxidative stress, and this effect could be blocked using antioxidants or by preventing ox-LDL from binding to its receptor. These findings suggest that cardiovascular risk factors like high cholesterol may directly contribute to osteoarthritis progression, indicating that managing cholesterol levels and oxidative stress could be important therapeutic targets for preventing cartilage degeneration in osteoarthritis patients.

DIVERGENT EFFECTS OF INFLIXIMAB AND ANAKINRA THERAPIES ON MACROPHAGE PHENOTYPE FROM PATIENTS WITH REFRACTORY RHEUMATOID ARTHRITIS.

This study investigated how two different rheumatoid arthritis (RA) treatments affect inflammatory cell behavior in patients with severe, treatment-resistant RA. Researchers compared the effects of infliximab (which blocks TNF-alpha) and anakinra (which blocks IL-1) on macrophages (immune cells) from patients' blood, specifically examining how these treatments influenced the cells' ability to produce nitric oxide, an inflammatory molecule.

Both treatments improved patients' symptoms, but anakinra was more effective at reducing inflammation at the cellular level - it completely stopped macrophages from producing nitric oxide and significantly lowered nitric oxide levels in the blood, while infliximab did not have these effects. The study revealed that both TNF-alpha and IL-1 are needed for macrophages to develop their inflammatory, nitric oxide-producing characteristics.

These findings suggest that different RA medications work through distinct mechanisms and may be more suitable for different patient subgroups, potentially helping clinicians choose more targeted treatments. For physiotherapy practice, this research indicates that patients receiving anakinra may experience more complete reduction of underlying inflammation, which could influence rehabilitation outcomes and exercise tolerance.

PHENOTYPIC ALTERATIONS OF NEURONS THAT INNERVATE OSTEOARTHRITIC JOINTS IN RATS.

This study aimed to understand how nerve cells that sense pain change in osteoarthritis by examining specific protein markers in neurons that connect to arthritic knee joints in rats. Researchers induced arthritis in rats using a chemical injection, then used special labeling techniques to identify and analyze the pain-sensing neurons in the spinal ganglia that supply the knee joint. The key finding was that osteoarthritis caused significant changes in these neurons, including a 37% reduction in labeled nerve cells, enlargement of remaining nerve cell bodies, and most importantly, increased production of CGRP (a pain-signaling protein) particularly in medium and large-sized neurons. These neuronal changes represent a "phenotypic switch" where nerve cells alter their pain-processing characteristics in response to joint damage, which may explain why osteoarthritis pain can become chronic and difficult to manage, suggesting that effective physiotherapy and pain management strategies need to account for these underlying nerve changes rather than focusing solely on joint mechanics.

SHEDDING OF LARGE FUNCTIONALLY ACTIVE CD11/CD18 INTEGRIN COMPLEXES FROM LEUKOCYTE MEMBRANES DURING SYNOVIAL INFLAMMATION DISTINGUISHES THREE TYPES OF ARTHRITIS THROUGH DIFFERENTIAL EPITOPE EXPOSURE.

This study aimed to investigate how immune cell adhesion molecules (CD11/CD18 integrins) are shed from cell surfaces during joint inflammation and whether this differs between types of arthritis. The researchers analyzed synovial fluid and plasma samples from patients with rheumatoid arthritis, spondyloarthritis, and osteoarthritis, combined with laboratory experiments to understand the shedding process.

The key finding was that CD11/CD18 integrin shedding occurs in inflammatory arthritis types (rheumatoid arthritis and spondyloarthritis) but not in osteoarthritis, effectively distinguishing three distinct arthritis phenotypes based on their inflammatory profiles. The shedding process was driven by TNF-α, a major inflammatory protein, and the shed complexes varied in size and binding properties depending on the specific type of arthritis.

These findings suggest that osteoarthritis and inflammatory arthritis involve fundamentally different immune processes, which has important implications for targeted treatment approaches - TNF-α blocking therapies may be more relevant for inflammatory conditions, while osteoarthritis may require different therapeutic strategies focused on non-inflammatory mechanisms.

OXYCODONE/PARACETAMOL: A LOW-DOSE SYNERGIC COMBINATION USEFUL IN DIFFERENT TYPES OF PAIN.

This narrative review aimed to evaluate the effectiveness and safety of a fixed-dose combination of oxycodone and paracetamol for treating various types of chronic pain. The authors reviewed clinical evidence across multiple pain conditions including osteoarthritis, chronic musculoskeletal pain, neuropathic pain, cancer-related pain, and postoperative pain. The key finding was that this drug combination demonstrated effectiveness across diverse pain phenotypes - from pure nociceptive pain (like osteoarthritis) to mixed pain conditions with neuropathic components, suggesting it may work regardless of underlying pain mechanisms. For physiotherapy practice, this suggests that patients presenting with moderate-to-severe musculoskeletal pain who haven't responded to simpler medications may benefit from this combination therapy as part of a multimodal approach, though the review doesn't specifically address how this might interact with or complement rehabilitation interventions.

PREMATURE ARTHRITIS IS A DISTINCT TYPE II COLLAGEN PHENOTYPE: COMMENT ON THE ARTICLE BY KANNU ET AL.

I cannot provide a meaningful summary of this research as no abstract was provided. The title suggests this is a commentary piece discussing premature arthritis as a distinct phenotype related to type II collagen abnormalities, responding to work by Kannu and colleagues.

To write an accurate summary focusing on the study objective, methods, findings about phenotypes/subgroups, and implications for physiotherapy management, I would need access to the full abstract or article content.

If you can provide the abstract, I'd be happy to create the requested 3-4 sentence summary in plain language.

REST COREPRESSOR (COREST) REPRESSION INDUCES PHENOTYPIC GENE REGULATION IN ADVANCED OSTEOARTHRITIC CHONDROCYTES.

This study aimed to identify molecular mechanisms underlying changes in cartilage cell (chondrocyte) characteristics that occur during osteoarthritis progression. The researchers used advanced protein analysis techniques to compare normal and severely arthritic cartilage samples, then conducted laboratory experiments where they artificially reduced levels of a protein called CoREST in healthy cartilage cells.

The key finding was that CoREST levels were significantly reduced (by about 70%) in advanced osteoarthritic cartilage, and when CoREST was experimentally lowered in healthy cells, they began displaying disease-like characteristics - producing less healthy cartilage proteins (collagen II and aggrecan) and more of a protein associated with cartilage breakdown (collagen X). This suggests that CoREST acts as a protective factor that helps maintain healthy cartilage cell function, and its loss may contribute to different osteoarthritis disease patterns or subtypes characterized by varying degrees of cartilage deterioration.

CUSTOM CEMENTLESS THA IN PATIENTS WITH SKELETAL DYSPLASIA RESULTS IN LOWER APPARENT REVISION RATES THAN OTHER TYPES OF FEMORAL FIXATION.

This study aimed to evaluate the effectiveness of custom-made cementless femoral components in total hip arthroplasty (THA) for patients with skeletal dysplasia, comparing outcomes to other fixation methods. The researchers followed 25 patients (40 hip replacements) with skeletal dysplasia for an average of 10 years, measuring survival rates, function, and complications after surgery using specially designed implants.

The study identified that patients with skeletal dysplasia represent a distinct subgroup requiring hip replacement at a much younger age (average 37.5 years) due to their abnormal hip anatomy, making standard surgical techniques more challenging. Key findings showed that custom-made implants achieved a 92% survival rate for the femoral component and significantly improved function scores from 41 to 80 points, with only 10% requiring revision surgery.

These results suggest that patients with skeletal dysplasia benefit from individualized surgical approaches using custom-designed implants rather than standard components, potentially reducing the need for repeat surgeries and improving long-term outcomes in this challenging patient population.

RECOMMENDATIONS FOR STANDARDIZATION AND PHENOTYPE DEFINITIONS IN GENETIC STUDIES OF OSTEOARTHRITIS: THE TREAT-OA CONSORTIUM.

This study aimed to standardize osteoarthritis (OA) phenotype definitions across 28 research studies in the TREAT-OA consortium to reduce inconsistencies in genetic research. The researchers examined how different definitions of symptomatic and radiographic OA affected study results, tested various hip OA definitions in a large population study, and worked to create standardized definitions across multiple cohorts. They found that different OA definitions led to dramatically different research findings - for example, one hip OA definition showed no association with gender while another definition of the same condition showed a very strong association. After standardizing the radiographic OA definitions across nine studies, the variation in reported OA prevalence was greatly reduced, suggesting that consistent phenotype definitions are crucial for reliable research that can ultimately inform more personalized physiotherapy and management approaches for different OA subgroups.

NEW INTERMEDIATE PHENOTYPE BETWEEN MED AND DD CAUSED BY COMPOUND HETEROZYGOUS MUTATIONS IN THE DTDST GENE.

This study aimed to characterize a new genetic bone disorder by analyzing three brothers with unusual skeletal abnormalities caused by specific mutations in the DTDST gene. The researchers used genetic analysis, clinical examination, and radiographic imaging to document the patients' features and classify their condition. They identified a new intermediate phenotype between two known bone disorders (diastrophic dysplasia and multiple epiphyseal dysplasia), characterized by short stature, foot deformities, spinal abnormalities, hip problems, and notably severe early-onset osteoarthritis. This finding has important implications for physiotherapy and management, as patients with this genetic profile may require specialized treatment approaches that address both the skeletal deformities and the early development of severe joint arthritis.

THE INFRAPATELLAR FAT PAD OF PATIENTS WITH OSTEOARTHRITIS HAS AN INFLAMMATORY PHENOTYPE.

This study aimed to investigate whether the infrapatellar fat pad (IFP) - a fatty tissue inside the knee joint - has different inflammatory characteristics compared to regular subcutaneous fat in patients with knee osteoarthritis. Researchers collected paired samples of IFP and subcutaneous fat from 27 osteoarthritis patients and analyzed the types of inflammatory substances released and immune cells present in each tissue type.

The key finding was that the IFP displayed a distinctly inflammatory phenotype, secreting significantly higher levels of inflammatory molecules (including IL-6, adipsin, adiponectin, and visfatin) compared to subcutaneous fat. The IFP also contained different immune cell populations, with more mast cells, fewer T cells, and immune cells that were predominantly pro-inflammatory in nature.

These findings suggest that the IFP represents an important inflammatory subtype or phenotype in knee osteoarthritis, where this internal fat tissue actively contributes to joint inflammation. For physiotherapy and management, this highlights the potential importance of interventions that could reduce IFP inflammation, and suggests that patients with more inflammatory IFP involvement might benefit from targeted anti-inflammatory approaches alongside traditional rehabilitation strategies.

ELEVATED DICKKOPF-2 LEVELS CONTRIBUTE TO THE ABNORMAL PHENOTYPE OF HUMAN OSTEOARTHRITIC OSTEOBLASTS.

This study investigated why bone-forming cells (osteoblasts) from people with osteoarthritis behave abnormally and have poor bone formation ability. The researchers compared osteoblasts from healthy and osteoarthritic joints, measuring levels of signaling proteins and testing bone formation in laboratory cultures. They discovered that osteoarthritic osteoblasts have elevated levels of a protein called DKK2, which blocks normal bone formation pathways - this creates a distinct abnormal cellular phenotype compared to healthy bone cells. These findings suggest that targeting the TGF-β1/DKK2 pathway could potentially improve bone quality in osteoarthritis, though the direct implications for physiotherapy and rehabilitation approaches are not immediately clear from this cellular-level research.

OSTEOARTHRITIS: ALL TYPES OF TROUBLE--DEFINING OA IN THE GENOMIC ERA.

This study examines the challenge of defining osteoarthritis (OA) phenotypes for genetic research in the modern genomic era. The authors reviewed existing classification systems and found that the numerous, overlapping ways to define and categorize OA create significant complications for genetic studies trying to identify disease associations. The main finding is that this heterogeneity in OA definitions obscures clear patterns and makes it difficult to identify meaningful subgroups, though some new recommendations show promise for improving clarity. These findings suggest that standardized, consistent phenotyping guidelines are urgently needed to advance both genetic research and clinical management, which could ultimately lead to more personalized physiotherapy approaches based on clearer OA subgroup identification.

GENDER AND PREVALENCE OF KNEE OSTEOARTHRITIS TYPES IN ELDERLY KOREANS.

This study aimed to examine sex differences in knee osteoarthritis prevalence across different disease severity stages in elderly Koreans aged 65 and older. The researchers analyzed 696 participants using X-rays and statistical modeling to identify three distinct disease stages: mild radiographic changes, severe radiographic changes, and advanced disease requiring total knee replacement surgery. The study found that women had significantly higher rates of knee osteoarthritis at all severity levels, with female sex being the strongest risk factor - particularly for those needing knee replacement surgery (affecting 6.5% overall but disproportionately more women). These findings suggest that elderly Korean women represent a high-risk phenotype requiring targeted prevention strategies and early physiotherapy interventions to potentially delay disease progression and reduce the need for surgical treatment.

DIABETES-INDUCED OSTEOARTHRITIS: FROM A NEW PARADIGM TO A NEW PHENOTYPE.

This study proposes a new concept that diabetes may directly cause osteoarthritis (OA) in certain patients, rather than just being associated with it. The researchers reviewed epidemiological and experimental evidence to support the hypothesis that diabetes acts as an independent risk factor for developing OA. Their findings suggest there may be a distinct "diabetes-induced OA" phenotype - a specific subgroup of OA patients whose joint disease is directly triggered by their diabetes. If this diabetes-induced phenotype is confirmed through further research, it could revolutionize how we prevent and treat OA by targeting diabetes management as a primary strategy to stop joint disease from starting or worsening.

THE EFFECTS OF NSAIDS ON TYPES I, II, AND III COLLAGEN METABOLISM IN A RAT OSTEOARTHRITIS MODEL.

This study investigated how long-term use of three different NSAIDs (celecoxib, ibuprofen, and indomethacin) affects collagen production in joint cartilage using a rat model of osteoarthritis. Researchers surgically induced osteoarthritis in 130 rats and examined cartilage tissue at 3, 6, and 9 months using microscopy and specialized staining techniques to measure different types of collagen. The findings revealed distinct effects for each NSAID: celecoxib had minimal impact on collagen metabolism, ibuprofen increased all collagen types, while indomethacin reduced beneficial type II collagen but increased potentially problematic types I and III collagen. These results suggest that for patients requiring long-term NSAID treatment, celecoxib may be the safest choice for preserving cartilage health, while indomethacin could potentially worsen joint degeneration - important considerations for physiotherapists and clinicians managing chronic osteoarthritis.

NO DIFFERENCES IN IN VIVO KINEMATICS BETWEEN SIX DIFFERENT TYPES OF KNEE PROSTHESES.

This study aimed to compare how six different types of total knee replacement prostheses move during real-world activities, testing whether different design features (like fixed vs. mobile bearings or cruciate-retaining vs. sacrificing) produce distinct movement patterns. Researchers used fluoroscopy to record knee movements in 52 patients with rheumatoid arthritis or osteoarthritis as they performed step-up exercises, analyzing various prosthetic designs including multi-radius, single-radius, fixed-bearing, mobile-bearing, and different cruciate ligament management approaches.

The main finding was that despite theoretical design differences, there were no clear, recognizable differences in how the different prostheses actually moved during activity, with one exception (NexGen group) showing reduced knee flexion and smaller movements. This suggests that the various design features of current total knee replacements do not translate into meaningfully different movement patterns that would affect patient outcomes.

For physiotherapy and rehabilitation, this implies that post-surgical exercise programs and movement retraining approaches may not need to be substantially modified based on the specific type of prosthesis used, since functional kinematics appear relatively consistent across different implant designs.

INTERLEUKIN-1Α, -6, AND -8 DECREASE CDC42 ACTIVITY RESULTING IN LOSS OF ARTICULAR CHONDROCYTE PHENOTYPE.

This study aimed to investigate how inflammatory molecules (interleukins IL-1α, IL-6, and IL-8) affect cartilage cells by examining their impact on CDC42, a protein that controls cell shape and function. Researchers exposed cartilage cells to these inflammatory molecules for different time periods and measured changes in gene expression, CDC42 activity, and cell structure using molecular techniques and microscopy. The key finding was that all three interleukins decreased CDC42 activity, leading to harmful changes in cartilage cells - they produced less healthy cartilage components (collagen and aggrecan) and more destructive enzymes, while also developing abnormal stress fibers that altered their shape. These results suggest that inflammation in osteoarthritis may damage cartilage not just through direct tissue breakdown, but also by fundamentally changing how cartilage cells behave, which could inform the development of treatments that target these cellular changes rather than just managing symptoms.

HIGH MOBILITY GROUP BOX PROTEIN 1 IN COMPLEX WITH LIPOPOLYSACCHARIDE OR IL-1 PROMOTES AN INCREASED INFLAMMATORY PHENOTYPE IN SYNOVIAL FIBROBLASTS.

This study investigated how a protein called HMGB1 works together with other inflammatory molecules to promote inflammation in joint cells from arthritis patients. Researchers exposed synovial fibroblasts (cells lining the joints) from both rheumatoid arthritis and osteoarthritis patients to HMGB1 combined with various inflammatory triggers, then measured the production of inflammatory chemicals and tissue-damaging enzymes.

The key finding was that HMGB1 significantly amplified the inflammatory response in both disease types, boosting production of inflammatory molecules like TNF, IL-6, and IL-8, as well as matrix metalloproteinases that break down joint tissue. This suggests that both rheumatoid arthritis and osteoarthritis patients may share a common inflammatory phenotype characterized by enhanced HMGB1-driven inflammation.

These findings indicate that targeting HMGB1 could be a promising therapeutic approach for managing inflammation in both types of arthritis, potentially informing rehabilitation strategies that address the underlying inflammatory processes driving joint damage and symptoms.

ASSOCIATION BETWEEN THE CHONDROCYTE PHENOTYPE AND THE EXPRESSION OF ADIPOKINES AND THEIR RECEPTORS: EVIDENCE FOR A ROLE OF LEPTIN BUT NOT ADIPONECTIN IN THE EXPRESSION OF CARTILAGE-SPECIFIC MARKERS.

This study investigated how changes in cartilage cell (chondrocyte) characteristics affect the production of fat-derived hormones called adipokines and their ability to respond to these signals. Researchers examined chondrocytes from osteoarthritis patients under different culture conditions and measured the expression of leptin, adiponectin, and cartilage-specific genes.

The findings revealed that chondrocytes exist in different states or "phenotypes" that dramatically influence their adipokine production and responsiveness - cells grown in flat cultures lost their cartilage-like properties and switched from producing adipokines to producing their receptors, while 3D culture restored normal cartilage characteristics. Importantly, only leptin (not adiponectin) was found to promote healthy cartilage marker expression through specific cellular signaling pathways.

These results suggest that the contradictory effects of adipokines in cartilage research may be explained by different chondrocyte phenotypes, and highlight leptin's potential therapeutic importance for maintaining cartilage health in osteoarthritis management.

IDENTIFICATION OF PHENOTYPES WITH DIFFERENT CLINICAL OUTCOMES IN KNEE OSTEOARTHRITIS: DATA FROM THE OSTEOARTHRITIS INITIATIVE.

This study aimed to identify distinct subgroups of knee osteoarthritis patients based on clinical characteristics and compare their outcomes. Researchers analyzed data from 842 patients using cluster analysis based on four key factors: X-ray severity, leg muscle strength, body weight, and depression levels. They identified five distinct phenotypes: minimal joint disease, strong muscle, non-obese with weak muscle, obese with weak muscle, and depressive phenotypes. The depressive and obese-weak muscle groups experienced significantly more pain and activity limitations, suggesting that physiotherapy and treatment approaches should be tailored to target the specific combination of factors present in each patient's phenotype rather than using a one-size-fits-all approach.

DIFFERENCES IN MULTIJOINT RADIOGRAPHIC OSTEOARTHRITIS PHENOTYPES AMONG AFRICAN AMERICANS AND CAUCASIANS: THE JOHNSTON COUNTY OSTEOARTHRITIS PROJECT.

This study aimed to identify and compare patterns of osteoarthritis affecting multiple joints between African Americans and Caucasians using X-ray data from 1,419-2,083 participants in the Johnston County Osteoarthritis Project. Researchers analyzed X-rays of hands, knees, hips, and spine to identify 16 distinct hand OA patterns and 32 whole-body OA patterns, then compared how frequently these patterns occurred between racial groups.

The study found significant racial differences in OA patterns: African Americans had less frequent hand OA (especially in finger tip joints) but more than twice the likelihood of isolated knee OA and 77% higher odds of combined knee and spine OA compared to Caucasians. These differences persisted even after accounting for age, sex, and body weight.

These findings suggest that African Americans may experience a different type of "generalized OA" that primarily affects large joints (knees, spine) rather than hands, which could require different physiotherapy approaches focusing more on weight-bearing joint function, mobility, and strength training for the lower body and spine.

LOSS OF MATRILIN 1 DOES NOT EXACERBATE THE SKELETAL PHENOTYPE IN A MOUSE MODEL OF MULTIPLE EPIPHYSEAL DYSPLASIA CAUSED BY A MATN3 V194D MUTATION.

This study investigated whether removing matrilin 1 protein would worsen the skeletal problems in a mouse model of multiple epiphyseal dysplasia (MED), a genetic condition causing abnormal bone growth and early arthritis. The researchers bred mice with a specific matrilin 3 gene mutation (V194D) with mice lacking matrilin 1, then examined bone development, cartilage structure, and protein behavior using various laboratory techniques. They found that eliminating matrilin 1 did not make the skeletal abnormalities worse, and the mutant matrilin 3 protein could still be secreted from cells even without matrilin 1 present. These findings suggest that matrilin 1 is not a key factor in determining disease severity in this type of MED, which may help researchers focus on other therapeutic targets for managing this condition that leads to early-onset osteoarthritis.

PREVALENCE OF MAGNETIC RESONANCE IMAGING-DEFINED ATROPHIC AND HYPERTROPHIC PHENOTYPES OF KNEE OSTEOARTHRITIS IN A POPULATION-BASED COHORT.

This study aimed to identify different patterns of knee osteoarthritis by examining the relationship between bone spurs (osteophytes) and cartilage damage using MRI scans in over 1,500 knees from a community-based population. The researchers used detailed MRI scoring to classify knees into two distinct phenotypes: "atrophic" (severe cartilage damage with minimal bone spurs) and "hypertrophic" (large bone spurs with minimal cartilage damage). The study found that larger bone spurs were strongly associated with more severe cartilage damage, with the atrophic phenotype present in only 1.3% of knees and the hypertrophic phenotype extremely rare at 0.2%. These findings suggest that most knee osteoarthritis follows a typical pattern where cartilage damage and bone changes occur together, but the small subset with atrophic phenotype (cartilage loss without bone changes) may represent a distinct disease process that could require different physiotherapy approaches focused on cartilage protection rather than managing bone-related symptoms.

TESTING TWO TYPES OF SELF-HELP CBT-I FOR INSOMNIA IN OLDER ADULTS WITH ARTHRITIS OR CORONARY ARTERY DISEASE.

This study compared two self-help formats of cognitive-behavioral therapy for insomnia (CBT-I) in 106 older adults, including 33 with osteoarthritis, 33 with coronary artery disease, and 40 without significant medical conditions. Participants were randomly assigned to either a book-based or multimedia version of CBT-I, with sleep outcomes measured through sleep logs and global sleep assessments. Both treatment formats effectively improved sleep in all groups, with benefits maintained at one-year follow-up, and importantly, people with osteoarthritis responded just as well as those without medical conditions. These findings suggest that self-help CBT-I could serve as an accessible, cost-effective first-line treatment for sleep problems in older adults with osteoarthritis, potentially complementing physiotherapy and other management approaches without requiring intensive therapist involvement.

PHENOTYPIC SPECTRUM OF THE SMAD3-RELATED ANEURYSMS-OSTEOARTHRITIS SYNDROME.

This study aimed to characterize the clinical features of aneurysms-osteoarthritis syndrome (AOS), a genetic condition caused by SMAD3 gene mutations that combines heart problems with joint disease. The researchers screened 393 patients with aneurysms for SMAD3 mutations and performed detailed medical examinations on 45 patients from 8 families who had confirmed mutations.

The study identified two main phenotypic patterns: most patients first sought medical care for early-onset joint problems including osteoarthritis and cartilage damage, while nearly 90% also had cardiovascular abnormalities including dangerous aortic aneurysms throughout the body. Critically, 20% of patients who initially presented with joint symptoms later died suddenly from aortic rupture, highlighting the life-threatening nature of this condition.

For physiotherapy and management, this research emphasizes that patients presenting with early-onset osteoarthritis should be screened for associated features like mild facial abnormalities, as early identification could prevent sudden cardiac death through appropriate cardiovascular monitoring and intervention.

MOLECULAR DIFFERENTIATION BETWEEN OSTEOPHYTIC AND ARTICULAR CARTILAGE--CLUES FOR A TRANSIENT AND PERMANENT CHONDROCYTE PHENOTYPE.

**Study Summary:**

This study aimed to identify molecular differences between two types of cartilage cells: those in osteophytes (bone spurs) versus normal joint cartilage, to understand why some cartilage cells remain stable while others change over time. Researchers analyzed gene expression patterns in cartilage samples from 15 human knee joints using advanced molecular techniques including microarray analysis and microscopy. The study revealed distinct cellular phenotypes - osteophyte cartilage cells expressed genes promoting bone formation and tissue breakdown (like osteocalcin and matrix enzymes), while normal joint cartilage cells expressed genes that actively prevent bone formation and maintain cartilage stability (like gremlin-1 and SOX9). These findings suggest that understanding these different cartilage cell types could help develop targeted treatments - potentially promoting the "stable" cartilage phenotype while preventing the "transient" phenotype that leads to problematic bone spur formation in osteoarthritis management.

OSTEOARTHRITIS: METABOLOMIC CHARACTERIZATION OF METABOLIC PHENOTYPES IN OA.

I apologize, but I cannot provide a meaningful summary of this research as the abstract is listed as "NA" (not available).

To write an accurate summary focusing on the study objective, methods, findings about metabolic phenotypes in osteoarthritis, and implications for physiotherapy management, I would need access to the actual abstract content.

If you could provide the complete abstract, I would be happy to create a concise 3-4 sentence summary in plain language covering the key points you've requested regarding metabolomic phenotyping in osteoarthritis research.

PHENOTYPIC AND GENETIC EVALUATION OF ELBOW DYSPLASIA IN DUTCH LABRADOR RETRIEVERS, GOLDEN RETRIEVERS, AND BERNESE MOUNTAIN DOGS.

This study aimed to evaluate the prevalence, genetic factors, and characteristics of elbow dysplasia in three dog breeds to better understand disease patterns and inheritance. Researchers examined radiographs from over 4,800 dogs (Labrador Retrievers, Golden Retrievers, and Bernese Mountain Dogs) between 2002-2009, assessing for four types of elbow developmental diseases and signs of arthritis using standardized imaging protocols.

The study identified distinct breed-specific phenotypes: fragmented medial coronoid process (FCP) was the most common form across all breeds, but Bernese Mountain Dogs showed the highest incidence (15%) while having the lowest genetic heritability, and male Labradors were 1.7 times more likely to develop osteoarthritis than females. Sclerosis at the base of the medial coronoid process emerged as a highly reliable radiographic marker for FCP diagnosis across all breeds.

These findings suggest that elbow dysplasia management should be tailored by breed and sex, with particular attention to early detection in high-risk populations like male Labradors and Bernese Mountain Dogs, and emphasize the importance of accurate imaging techniques for proper diagnosis and treatment planning.

PHENOTYPIC CHARACTERIZATION OF OSTEOARTHRITIC OSTEOCYTES FROM THE SCLEROTIC ZONES: A POSSIBLE PATHOLOGICAL ROLE IN SUBCHONDRAL BONE SCLEROSIS.

This study aimed to investigate how osteocytes (bone cells) change in osteoarthritis and whether these changes contribute to the bone thickening (sclerosis) commonly seen beneath joint cartilage in OA patients. The researchers used multiple laboratory techniques including imaging, microscopy, and genetic analysis to compare osteocytes from OA patients with healthy controls. They found that OA osteocytes had distinctly altered shapes (rounder with fewer connecting branches), showed signs of cell death, and had disrupted gene expression patterns, which coincided with abnormal bone remodeling and increased bone volume in affected areas. These findings suggest that targeting osteocyte dysfunction could be important for developing treatments that address the bone changes in OA, potentially informing rehabilitation strategies that consider both cartilage and underlying bone health rather than focusing solely on joint surface problems.

STRUCTURED THREE-DIMENSIONAL CO-CULTURE OF MESENCHYMAL STEM CELLS WITH MENISCUS CELLS PROMOTES MENISCAL PHENOTYPE WITHOUT HYPERTROPHY.

This study aimed to investigate whether co-culturing mesenchymal stem cells (MSCs) with mature meniscus cells could effectively create meniscus tissue for potential transplantation in patients with meniscus damage. The researchers tested different ratios of these cell types (ranging from 100% meniscus cells to 100% stem cells) in laboratory pellets and measured the production of meniscus-specific proteins and structures over 21 days.

The key finding was that a 75:25 ratio of meniscus cells to stem cells produced the best results, creating the highest amounts of important meniscus components (collagen type I and glycosaminoglycans) while avoiding unwanted tissue changes that could lead to problems. All co-culture combinations performed better than using stem cells alone, successfully creating the fiber bundle structures that are essential for proper meniscus function.

This research suggests that tissue engineering using this specific cell combination could offer a promising treatment alternative to current meniscus removal surgeries, which often lead to knee osteoarthritis. For physiotherapy practice, this could eventually mean patients with meniscus tears might have regenerative treatment options that preserve knee joint health, potentially reducing the need for long-term osteoarthritis management strategies.

A ROLE FOR PACE4 IN OSTEOARTHRITIS PAIN: EVIDENCE FROM HUMAN GENETIC ASSOCIATION AND NULL MUTANT PHENOTYPE.

This study investigated whether genetic variations in the PACE4 gene (PCSK6) influence pain symptoms in people with knee osteoarthritis. Researchers analyzed genetic data from over 2,700 people with radiographic knee OA across four cohorts, comparing those with and without pain symptoms, and also tested pain responses in genetically modified mice lacking the PACE4 gene.

The study identified a specific genetic variant (rs900414) that was more common in people who had knee OA on X-rays but experienced no pain symptoms, suggesting this variant provides protection against OA pain. Mice without the PACE4 gene also showed significantly reduced pain responses in laboratory pain tests, supporting the genetic findings in humans.

These findings help explain why some people with similar joint damage on X-rays experience chronic pain while others remain pain-free, identifying a potential "pain-protected" phenotype in osteoarthritis. This discovery could lead to new approaches for managing OA pain and may help physiotherapists and clinicians better predict which patients are likely to develop chronic pain symptoms, allowing for more personalized treatment strategies.

DIABETES-INDUCED OSTEOARTHRITIS: FROM A NEW PARADIGM TO A NEW PHENOTYPE.

This article proposes that diabetes may be an independent risk factor for developing osteoarthritis (OA) in certain patients, suggesting a distinct "diabetes-induced OA phenotype." The authors reviewed epidemiological and experimental evidence supporting this connection between diabetes and OA development. Their findings indicate that diabetes could directly contribute to OA initiation and progression, representing a new way of understanding OA beyond traditional mechanical causes. If this diabetes-related OA phenotype is confirmed, it could significantly change how clinicians prevent and manage OA, potentially requiring integrated diabetes management alongside standard musculoskeletal treatments in physiotherapy practice.

DISCRIMINATION OF MENISCAL CELL PHENOTYPES USING GENE EXPRESSION PROFILES.

This study aimed to identify measurable genetic markers that could distinguish between different types of meniscal cells to improve tissue engineering approaches for cartilage repair. Researchers analyzed gene expression patterns in cells from different regions (cartilage, inner, middle, and outer meniscus) and found that three specific gene ratios (collagen VI/collagen II, ADAMTS-5/collagen II, and collagen I/collagen II) were most effective at identifying cell types based on their tissue origin. The findings revealed distinct cellular phenotypes across different meniscal regions, providing objective tools to evaluate and optimize cell-based treatments for cartilage damage. These genetic markers could help clinicians and researchers better understand how meniscal tissue degrades in osteoarthritis and develop more targeted rehabilitation strategies or tissue engineering treatments tailored to specific areas of the meniscus.

THE BONE DYSPLASIA ONTOLOGY: INTEGRATING GENOTYPE AND PHENOTYPE INFORMATION IN THE SKELETAL DYSPLASIA DOMAIN.

This study aimed to develop a comprehensive digital framework called the Bone Dysplasia Ontology to organize and integrate scattered knowledge about rare genetic skeletal disorders. The researchers created a structured database system that formally categorizes skeletal dysplasias along with their associated genetic causes and physical characteristics, and built a user-friendly platform called Skeletome where medical experts can contribute and access this information without needing technical expertise.

The ontology successfully identified and organized different phenotypic subgroups of skeletal dysplasias by linking specific genetic variations to their corresponding physical manifestations and complications, including joint degeneration and neurological problems. This comprehensive classification system enables better understanding of how these rare conditions present differently across patients and helps identify distinct disease patterns.

For physiotherapy and clinical management, this tool could significantly improve treatment planning by allowing therapists to access detailed information about specific skeletal dysplasia subtypes, understand their typical complications, and learn from similar cases to develop more targeted rehabilitation approaches for these complex rare conditions.

ISOLATION AND PHENOTYPIC CHARACTERISATION OF STEM CELLS FROM LATE STAGE OSTEOARTHRITIC MESENCHYMAL TISSUES.

This study aimed to investigate whether mesenchymal stem cells (MSCs) with regenerative potential could be found in tissues from patients with severe knee osteoarthritis requiring joint replacement surgery. Researchers collected samples from three different tissue types (bone, joint lining, and fat tissue around the joint) during knee replacement operations and tested the cells' ability to grow, multiply, and transform into different tissue types like bone, fat, and cartilage.

The findings showed that all three tissue types contained functional stem cells capable of regeneration, but cells from different tissues behaved differently - particularly, stem cells from fat tissue grew faster and were more active than those from bone or joint lining tissues. Importantly, these differences were consistent based on tissue type rather than varying between individual patients.

These results suggest that even in severely damaged arthritic joints, there are still viable stem cells that could potentially be harvested and used for regenerative treatments, offering hope for developing personalized therapies using a patient's own cells rather than requiring external cell sources.

LEAD INDUCES AN OSTEOARTHRITIS-LIKE PHENOTYPE IN ARTICULAR CHONDROCYTES THROUGH DISRUPTION OF TGF-Β SIGNALING.

This study investigated whether lead exposure causes cartilage damage that resembles osteoarthritis by disrupting normal cell signaling in joint cartilage cells (chondrocytes). Researchers exposed cartilage cells to various lead concentrations both in laboratory cultures and in living animals, then measured changes in cell behavior, cartilage proteins, and key signaling pathways that normally maintain healthy joints.

Lead exposure produced changes strikingly similar to osteoarthritis, including breakdown of the joint surface, decreased production of healthy cartilage protein (type II collagen), increased production of unhealthy cartilage protein (type X collagen), and elevated activity of enzymes that break down cartilage matrix. The researchers found that lead disrupted TGF-β signaling, a crucial pathway that normally helps maintain healthy cartilage, with up to 95% reduction in this protective signaling at higher lead doses.

These findings suggest that environmental lead exposure may be an underrecognized risk factor for developing osteoarthritis-like joint damage. For physiotherapy and joint health management, this research highlights the importance of considering environmental factors in osteoarthritis development and may support targeted interventions to protect cartilage signaling pathways in patients with known lead exposure.

CARRAGEENAN-INDUCED TRANSIENT INFLAMMATION IN A RABBIT KNEE MODEL: MOLECULAR CHANGES CONSISTENT WITH AN EARLY OSTEOARTHRITIS PHENOTYPE.

This animal study aimed to investigate whether acute knee inflammation triggers molecular changes associated with early osteoarthritis development. Researchers injected carrageenan (an inflammatory substance) into rabbit knees and measured inflammatory markers and cartilage-degrading enzymes at 1, 2, and 4 weeks post-injection. The study found that inflammation peaked at 2 weeks with elevated levels of inflammatory cytokines (IL-1β, IL-6) and cartilage-destroying enzymes (MMPs, cathepsin K), but these returned to normal by 4 weeks, with the tibial plateau cartilage showing stronger responses than other knee areas. The findings suggest that while acute inflammation can trigger early osteoarthritis-like molecular changes, a single inflammatory episode alone may not lead to chronic joint disease, indicating that physiotherapy and rehabilitation strategies should address multiple factors including ongoing mechanical issues and repeated injuries rather than focusing solely on initial inflammation management.

MITOCHONDRIAL HAPLOGROUPS DEFINE TWO PHENOTYPES OF OSTEOARTHRITIS.

This study investigated whether mitochondrial DNA variations (haplogroups H and J) create distinct osteoarthritis (OA) subtypes by analyzing blood levels of cartilage breakdown markers in 48 OA patients and 52 healthy controls. Researchers measured multiple biomarkers related to cartilage destruction and used statistical models to identify patterns that could predict OA diagnosis in each genetic group. The findings revealed two distinct OA phenotypes: patients with haplogroup H showed elevated levels of multiple collagen breakdown markers and could be diagnosed using a combination of MMP-13 and COLL2-1 markers, while those with haplogroup J only showed elevated MMP-13 levels. These results suggest that genetic testing combined with specific blood markers could enable personalized OA diagnosis and potentially guide tailored treatment approaches, though the study doesn't directly address specific physiotherapy implications.

AGGRESSIVE CARDIOVASCULAR PHENOTYPE OF ANEURYSMS-OSTEOARTHRITIS SYNDROME CAUSED BY PATHOGENIC SMAD3 VARIANTS.

This study aimed to characterize the cardiovascular features of Aneurysms-Osteoarthritis Syndrome (AOS), a genetic condition caused by SMAD3 gene variants that combines heart/blood vessel problems with joint arthritis. Researchers conducted comprehensive cardiovascular assessments on 44 AOS patients from 7 families, including imaging scans, artery stiffness measurements, and blood tests. The findings revealed an aggressive cardiovascular phenotype, with 71% having aortic aneurysms, 33% having aneurysms elsewhere, and a high mortality rate (mean age 54 years) primarily due to aortic ruptures that occurred even when aneurysms were only mildly enlarged. For physiotherapy and management, this suggests that AOS patients require specialized care protocols that account for their fragile cardiovascular system, with early surgical intervention recommended for aortic aneurysms and careful monitoring needed during any physical rehabilitation due to the high risk of life-threatening complications.

TYPE II TGFΒ RECEPTOR MODULATES CHONDROCYTE PHENOTYPE.

This laboratory study investigated how a specific cellular receptor (type II TGFβ receptor) influences cartilage cell behavior and characteristics in osteoarthritis. The researchers used human cartilage cells and stem cells in laboratory cultures, manipulating cellular conditions to study how cells change from healthy cartilage-producing cells to less functional forms and back again.

The key finding was that when cartilage cells lose their healthy characteristics (as happens in aging and osteoarthritis), they also lose this important receptor, which normally helps maintain proper cartilage function. When researchers restored the receptor or grew cells in 3D conditions that promote healthy cartilage formation, the cells regained their ability to produce key cartilage components like collagen and aggrecan.

These findings suggest there are distinct cellular subgroups in osteoarthritis based on receptor expression levels and cartilage-producing capability. For physiotherapy and rehabilitation, this research points toward the potential importance of mechanical loading and conditions that promote the 3D cartilage environment, as these may help maintain or restore healthy cartilage cell function through this receptor pathway.

A PROSPECTIVE, RANDOMIZED COMPARISON OF 3 TYPES OF PROXIMAL INTERPHALANGEAL JOINT ARTHROPLASTY.

This study aimed to compare three different implant types (titanium-polyethylene, pyrocarbon, and silicone) for finger joint replacement surgery in patients with osteoarthritis of the proximal interphalangeal joints. The researchers conducted a randomized trial with 43 patients (62 joints) across three centers, measuring outcomes including pain, range of motion, strength, and complications over approximately 3 years. All three implant types successfully reduced pain and slightly improved grip strength, with the newer surface replacement devices (titanium-polyethylene and pyrocarbon) showing temporarily better joint mobility compared to traditional silicone spacers, though this difference was not statistically significant. However, the newer implants had much higher complication rates requiring removal (27-39% vs 11% for silicone), suggesting that while silicone spacers may not restore optimal joint function, they remain a safer option for hand osteoarthritis management and may be preferable when considering risk-benefit ratios in rehabilitation planning.

BONE PARAMETERS ACROSS DIFFERENT TYPES OF HIP OSTEOARTHRITIS AND THEIR RELATIONSHIP TO OSTEOPOROTIC FRACTURE RISK.

This study aimed to compare bone characteristics and fracture risk between different hip osteoarthritis (OA) phenotypes, specifically examining the less-studied atrophic type (cartilage breakdown without bone spurs) versus osteophytic types (with bone spurs). Using data from 5,006 participants in the Rotterdam Study followed for nearly 10 years, researchers measured bone mineral density, hip structure, and tracked osteoporotic fractures across OA subtypes.

The key finding was that people with atrophic hip OA had systematically lower bone density throughout their body (6-9% lower) and nearly 50% higher risk of osteoporotic fractures compared to controls, while those with osteophytic OA actually had stronger, denser bones. Importantly, the increased fracture risk in atrophic OA couldn't be fully explained by lower bone density alone, suggesting other factors are involved.

For physiotherapy practice, this highlights the need to identify OA phenotypes early, as patients with atrophic hip OA may require more intensive fall prevention programs and bone health interventions beyond standard OA management.

DISPARITY IN PREOPERATIVE PATIENT FACTORS BETWEEN INSURANCE TYPES IN TOTAL JOINT ARTHROPLASTY.

This study examined how insurance type affects patient characteristics and functional status before hip or knee replacement surgery. Researchers analyzed 1,312 patients undergoing joint replacement, grouping them by insurance type (state indigent care, Medicare, Medicaid, or private insurance) and comparing their demographics, function scores, and access to care.

The study found clear differences between insurance groups, with patients having state indigent care or Medicaid showing significantly worse function scores, higher smoking rates, higher body weight, and needing to travel much farther (about 30 miles more) to receive care compared to those with Medicare or private insurance. Insurance type independently predicted how poorly patients functioned before surgery, suggesting these represent distinct patient subgroups with different baseline characteristics.

These findings highlight important healthcare disparities that could influence rehabilitation outcomes, suggesting that patients with public insurance may need more intensive pre- and post-surgical support, including smoking cessation programs, weight management, and potentially modified physiotherapy approaches to address their worse starting functional status.

MIGFILIN'S ELIMINATION FROM OSTEOARTHRITIC CHONDROCYTES FURTHER PROMOTES THE OSTEOARTHRITIC PHENOTYPE VIA Β-CATENIN UPREGULATION.

This study aimed to investigate the role of cell-ECM adhesion proteins, particularly migfilin, in osteoarthritis development by comparing cartilage cells from healthy individuals and OA patients. The researchers used primary human articular chondrocytes and examined expression levels of various adhesion molecules, then tested what happened when migfilin was experimentally reduced in OA cells.

The key finding was that migfilin levels were elevated in OA cartilage cells, but surprisingly, when researchers eliminated migfilin from these cells, it made the osteoarthritic features worse rather than better - increasing cartilage-degrading markers and reducing protective cartilage components like aggrecan. The study also revealed that migfilin works inversely with β-catenin, a protein involved in cartilage breakdown.

These findings suggest that migfilin may actually serve a protective role in OA, challenging assumptions about elevated proteins always being harmful, and highlight the complex molecular mechanisms underlying different OA phenotypes that could inform future targeted therapies and rehabilitation strategies.

RADIOGRAPHIC HIP JOINT PHENOTYPE OF THE PEMBROKE WELSH CORGI.

This study investigated the hip joint characteristics of Pembroke Welsh Corgis using X-rays from 399 dogs to understand their unique bone structure patterns. Researchers measured joint looseness and examined various signs of hip problems including arthritis, subluxation (partial dislocation), and specific types of bone growths called osteophytes. Despite having loose hip joints that typically predict arthritis in larger dogs, Corgis showed surprisingly low rates of conventional arthritis (6.8%), though they had high rates of circumferential bone growths around the hip (74.4%). This suggests that small, short-legged dog breeds like Corgis may need different assessment and management approaches for hip problems compared to larger breeds, as their joint looseness doesn't follow the same patterns of disease development.

ENHANCED HYALINE CARTILAGE MATRIX SYNTHESIS IN COLLAGEN SPONGE SCAFFOLDS BY USING SIRNA TO STABILIZE CHONDROCYTES PHENOTYPE CULTURED WITH BONE MORPHOGENETIC PROTEIN-2 UNDER HYPOXIA.

This study aimed to develop a method for improving cartilage repair by restoring the proper cellular characteristics of chondrocytes (cartilage cells) that lose their identity during osteoarthritis or laboratory expansion for transplantation procedures. The researchers tested different combinations of treatments including low oxygen conditions, growth factors (BMP-2 and IGF-I), collagen scaffolds, and gene silencing techniques to encourage dedifferentiated chondrocytes to regain their cartilage-producing properties. They found that BMP-2 treatment combined with low oxygen and targeted gene silencing successfully restored the cells' ability to produce healthy cartilage matrix without unwanted bone formation, while IGF-I produced mixed results with some undesirable effects. This approach could significantly improve autologous chondrocyte implantation (ACI) therapies, offering patients with cartilage damage from trauma or arthritis better treatment outcomes through more effective tissue engineering strategies.

C-REACTIVE PROTEIN (CRP) IN DIFFERENT TYPES OF MINIMALLY INVASIVE KNEE ARTHROPLASTY.

This study aimed to compare C-reactive protein (CRP) levels—a marker of inflammation and surgical trauma—across three different types of minimally invasive knee replacement surgeries. Researchers tracked CRP levels in 372 patients at multiple time points after minimally invasive total knee replacement (MI TKA), patient-specific instrument-guided TKA (PSI TKA), and unicompartmental knee replacement (UKA).

The key finding was that patients receiving UKA (partial knee replacement) showed significantly lower peak inflammation levels and faster recovery compared to those receiving total knee replacements, while PSI-guided surgery showed no clear advantage over conventional minimally invasive techniques. Importantly, 18% of patients still had elevated CRP levels at 6 weeks post-surgery, which the researchers determined was normal healing rather than infection.

For physiotherapy practice, this suggests that patients undergoing UKA may experience less systemic inflammation and potentially tolerate rehabilitation better, while those with persistently elevated CRP at 6 weeks shouldn't automatically be suspected of having an infection, allowing for continued appropriate rehabilitation protocols.

A COMPARISON OF THE NOISE GENERATED FROM DIFFERENT TYPES OF KNEE PROSTHESES.

This study aimed to compare noise generation between different types of knee replacement prostheses following total knee arthroplasty (TKA). Researchers conducted a prospective study with 465 patients who received different randomly-selected prostheses in each knee, then surveyed patients about noise-related symptoms. The study identified distinct subgroups based on prosthesis type, with medial pivot (12% noise) and ACL-PCL retaining prostheses (4% noise) producing significantly less noise than PCL retaining (31%), posterior cruciate-substituting (33%), and mobile bearing designs (42%). These findings suggest that prosthesis selection could be an important consideration in surgical planning, as noise can cause patient concern and dissatisfaction, potentially informing both surgeon decision-making and post-operative patient education regarding expected outcomes.

OSTEOARTHRITIS IN 2012: PARALLEL EVOLUTION OF OA PHENOTYPES AND THERAPIES.

This 2012 review examined advances in personalized osteoarthritis treatment approaches and methods for identifying which patients would benefit most from specific therapies. The study focused on developments in targeted treatments alongside improved patient selection strategies rather than using specific research methods. The key finding was that osteoarthritis patients can be better categorized into distinct groups or phenotypes that respond differently to various treatments. These advances in phenotyping and targeted therapies represent important progress toward developing disease-modifying treatments for osteoarthritis, which could allow physiotherapists and clinicians to tailor rehabilitation approaches more effectively to individual patient characteristics and needs.

BRIEF REPORT: DIFFERENCES IN MULTIJOINT SYMPTOMATIC OSTEOARTHRITIS PHENOTYPES BY RACE AND SEX: THE JOHNSTON COUNTY OSTEOARTHRITIS PROJECT.

This study aimed to identify different patterns of osteoarthritis (OA) symptoms across multiple joints and examine how these patterns vary by race and sex. Researchers analyzed data from 1,650 community-dwelling adults, looking at symptomatic OA in four body regions: hands, knees, hips, and lower back spine, then compared the patterns of joint involvement between African Americans versus Caucasians and men versus women.

The study found distinct differences in OA patterns between groups: African Americans were less likely to have hand OA (alone or combined with other joints) but more likely to have knee-only OA compared to Caucasians, while men were less likely to have hand-only OA but more likely to have lower back spine-only OA compared to women. These findings suggest that OA affects different joints preferentially based on demographic characteristics, which could help clinicians better understand and predict OA patterns in their patients.

For physiotherapy practice, this research highlights the importance of considering race and sex when assessing and treating patients with OA, as different groups may benefit from targeted interventions focusing on their most commonly affected joints.

ADULT CARTILAGE-SPECIFIC PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA KNOCKOUT MICE EXHIBIT THE SPONTANEOUS OSTEOARTHRITIS PHENOTYPE.

This study aimed to investigate the specific role of PPARγ (a protein that regulates gene activity) in cartilage health and osteoarthritis development using genetically modified mice. Researchers created mice that lacked PPARγ specifically in their cartilage cells and examined their joints for signs of osteoarthritis compared to normal mice. The mice without PPARγ spontaneously developed severe osteoarthritis-like changes, including cartilage breakdown, joint inflammation, tissue scarring, and increased levels of harmful enzymes that destroy cartilage. These findings suggest that PPARγ is essential for maintaining healthy cartilage, and its absence creates an aggressive osteoarthritis phenotype, indicating that treatments targeting PPARγ activation could be promising therapeutic approaches for managing osteoarthritis progression in patients.

THORACIC AORTIC ANEURYSM IN INFANCY IN ANEURYSMS-OSTEOARTHRITIS SYNDROME DUE TO A NOVEL SMAD3 MUTATION: FURTHER DELINEATION OF THE PHENOTYPE.

This case study aimed to characterize a newly identified genetic condition called Aneurysms-Osteoarthritis Syndrome (AOS) caused by mutations in the SMAD3 gene. The researchers analyzed a family with multiple members affected by aortic aneurysms, using genetic testing to identify a novel SMAD3 mutation after ruling out other similar conditions. The key finding was that this family displayed severe aortic complications from infancy (requiring surgery as early as 12 months) but notably lacked the typical osteoarthritis features usually seen in AOS, expanding our understanding of how this condition can present. This has important implications for genetic screening and early cardiovascular monitoring in families with connective tissue disorders, even when joint problems are absent.

SIRT1-DEFICIENT MICE EXHIBIT AN ALTERED CARTILAGE PHENOTYPE.

This study investigated how SIRT1 gene deficiency affects cartilage health by comparing knockout mice to normal controls at different ages (1-3 weeks and 6 months). The researchers examined cartilage tissue samples and measured key cartilage components, breakdown enzymes, and cell death markers. They found that mice lacking SIRT1 had a distinct cartilage phenotype characterized by reduced protective cartilage components (collagen and aggrecan), increased cartilage-destroying enzymes (MMP-13), and higher rates of cartilage cell death. These findings suggest that SIRT1 plays a crucial role in maintaining healthy cartilage, and its deficiency may predispose to cartilage degeneration, potentially informing future therapeutic targets for preventing osteoarthritis progression.

ROLE OF HORMONES IN CARTILAGE AND JOINT METABOLISM: UNDERSTANDING AN UNHEALTHY METABOLIC PHENOTYPE IN OSTEOARTHRITIS.

This review aimed to define and characterize "metabolic osteoarthritis" as a distinct subtype linked to poor metabolic health. The authors reviewed existing literature to examine how hormones (particularly estrogen and thyroid hormones), along with cytokines and adipokines, affect cartilage and joint metabolism. They identified that metabolic syndrome creates hormonal imbalances that directly and indirectly damage joint tissues, particularly cartilage, leading to a metabolic phenotype of osteoarthritis that is especially common in postmenopausal women. The findings suggest that osteoarthritis management and physiotherapy should consider addressing underlying metabolic health issues, including hormonal imbalances and metabolic syndrome, rather than focusing solely on traditional mechanical factors like joint loading.

AN IMPRINTED RHEUMATOID ARTHRITIS METHYLOME SIGNATURE REFLECTS PATHOGENIC PHENOTYPE.

This study aimed to investigate whether rheumatoid arthritis (RA) cells have stable DNA methylation patterns that distinguish them from osteoarthritis (OA) and normal cells, and whether these patterns affect disease-relevant biological pathways. The researchers used advanced genetic analysis to compare methylation patterns in joint lining cells from RA, OA, and healthy individuals across multiple cell generations in the laboratory.

The key finding was that RA cells maintained distinct and stable methylation signatures that were enriched in pathways directly related to RA disease processes, including immune system dysfunction, inflammation, and cell adhesion - with the "rheumatoid arthritis pathway" being the most significantly affected. These epigenetic changes persisted even when cells were grown in culture for extended periods, suggesting they represent a stable "imprint" that contributes to the aggressive behavior of RA joint cells.

This research suggests that RA joint cells have fundamental epigenetic differences that drive their pathogenic behavior, potentially offering new therapeutic targets for modulating disease progression and informing more personalized treatment approaches for RA management.

IDENTIFYING PHENOTYPES OF KNEE OSTEOARTHRITIS BY SEPARATE QUANTITATIVE RADIOGRAPHIC FEATURES MAY IMPROVE PATIENT SELECTION FOR MORE TARGETED TREATMENT.

This study aimed to identify distinct patterns (phenotypes) of knee osteoarthritis progression using detailed X-ray measurements to help improve patient treatment selection. Researchers analyzed X-ray images from people with early knee osteoarthritis over 5 years, measuring specific features like joint space width, bone spurs, and bone density, then used statistical clustering to group patients with similar progression patterns. They identified five distinct phenotypes: "severe progression," "no progression," "early progression," "late progression," and one characterized mainly by "bone density changes," with each group showing different baseline X-ray characteristics that could predict which pattern a patient might follow. These findings suggest that patients with knee osteoarthritis could be grouped into specific subgroups based on their X-ray features, potentially allowing physiotherapists and clinicians to tailor treatments more precisely to each patient's likely progression pattern rather than using a one-size-fits-all approach.

TRANSCRIPTOME ANALYSIS OF INJURED HUMAN MENISCUS REVEALS A DISTINCT PHENOTYPE OF MENISCUS DEGENERATION WITH AGING.

This study aimed to understand how injured meniscus tissue responds differently based on patient age and the degree of knee cartilage damage by analyzing gene expression patterns in torn meniscus samples from 12 patients. Researchers used advanced genetic analysis techniques to examine tissue removed during arthroscopic surgery from patients who had meniscus tears but no signs of osteoarthritis on X-rays. The findings revealed two distinct patterns: older patients showed a shift toward inflammation and abnormal cell growth with reduced ability to maintain healthy cartilage tissue, while younger patients maintained better tissue repair responses despite injury. These results suggest that meniscus injuries in older adults may require different treatment approaches than those in younger patients, potentially informing age-specific rehabilitation strategies and highlighting why older patients may be at higher risk for developing osteoarthritis after meniscus tears.

JOINT AWARENESS IN DIFFERENT TYPES OF KNEE ARTHROPLASTY EVALUATED WITH THE FORGOTTEN JOINT SCORE.

This study aimed to validate a French version of the Forgotten Joint Score (FJS-12) questionnaire and compare how well patients can "forget" their artificial knee joint in daily activities across different types of knee replacement surgery. The researchers assessed 122 patients who had received either partial knee replacement targeting the inner compartment (unicompartmental), kneecap area only (patellofemoral), or complete knee replacement (total knee arthroplasty).

The main finding was that patients with unicompartmental and total knee replacements showed similar levels of joint awareness, while those with patellofemoral replacements had significantly higher joint awareness (lower "forgetting" scores). However, the poorer outcomes in the patellofemoral group appeared to be related to patient characteristics, as this group consisted of younger and smaller patients rather than the surgery type itself.

These results suggest that patient demographics may influence post-surgical joint awareness more than the specific type of knee replacement, which could help physiotherapists tailor rehabilitation expectations and approaches based on individual patient profiles rather than surgery type alone.

THE TRANSIENT CHONDROCYTE PHENOTYPE IN HUMAN OSTEOPHYTIC CARTILAGE: A ROLE OF PIGMENT EPITHELIUM-DERIVED FACTOR?

This study aimed to understand why chondrocytes (cartilage cells) in osteophytes (bone spurs) die and turn into bone, while normal joint cartilage cells survive for decades. The researchers compared gene expression between osteophyte cartilage and normal joint cartilage using microarray analysis, then validated their findings with additional laboratory techniques. They discovered that a protein called PEDF was expressed 118 times higher in osteophytes compared to normal cartilage, and this high PEDF level promoted cell death by increasing pro-death signals. These findings suggest that targeting PEDF or the cell death pathways it activates could potentially be a therapeutic approach to prevent osteophyte formation and progression in osteoarthritis, though this would require further research before clinical applications.

TWO PHENOTYPES OF ARTHROPATHY IN LONG-TERM CONTROLLED ACROMEGALY? A COMPARISON BETWEEN PATIENTS WITH AND WITHOUT JOINT SPACE NARROWING (JSN).

This study aimed to identify different types of joint problems in acromegaly patients by comparing those with and without joint space narrowing (JSN), a sign of cartilage loss. Researchers examined hip and knee X-rays from 89 well-controlled acromegaly patients and used statistical models to identify risk factors for JSN while accounting for age, sex, BMI, and patient-specific factors.

The study found two distinct phenotypes of acromegalic arthropathy: most patients had the typical pattern with bone spurs but preserved joint spaces, while a minority (10-15%) developed JSN. Risk factors for JSN differed by joint location - in hips, JSN was linked to more severe acromegaly (higher hormone levels, longer disease duration, incomplete surgical cure), while in knees, previous knee surgery was the main risk factor rather than acromegaly-specific factors.

These findings suggest that hip JSN represents a more severe form of acromegaly-related joint damage, while knee JSN may be more related to mechanical factors or previous trauma. For physiotherapy management, patients with JSN experience more joint symptoms and may require different treatment approaches, with hip involvement potentially indicating more systemic acromegaly-related joint damage requiring closer monitoring.

SERUM METABOLIC SIGNATURES OF FOUR TYPES OF HUMAN ARTHRITIS.

This study aimed to identify unique metabolic signatures in blood samples that could help distinguish between four major types of arthritis: rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and gout. Researchers used advanced mass spectrometry techniques to analyze 196 different metabolites in serum samples from 114 arthritis patients and 60 healthy controls. They discovered both a common metabolic pattern shared across all arthritis types (reflecting joint inflammation and damage) and distinct metabolic signatures specific to each arthritis subtype that could serve as diagnostic biomarkers. These findings suggest that metabolic profiling could become a valuable diagnostic tool to help clinicians better identify arthritis subtypes and develop more personalized treatment approaches, potentially improving physiotherapy and management strategies by enabling earlier and more accurate diagnosis.

NOCICEPTIVE PHENOTYPE OF DORSAL ROOT GANGLIA NEURONS INNERVATING THE SUBCHONDRAL BONE IN RAT KNEE JOINTS.

This study aimed to identify the specific nerve cell characteristics involved in pain from the subchondral bone (the bone layer beneath cartilage) in rat knee joints, which is a major source of osteoarthritis pain. The researchers used a tracking technique to label nerve cells and examined their pain-related markers, comparing subchondral bone nerves to general knee joint nerves. They found that subchondral bone pain nerves had distinct characteristics - 60% were located in the L3 spinal segment, and most expressed high levels of CGRP (50%) and TrkA (65%) pain markers, which was significantly different from regular knee joint nerves. These findings suggest that subchondral bone pain represents a specific pain phenotype in knee osteoarthritis, and treatments targeting CGRP and TrkA pathways could provide more effective pain relief for patients with bone-related knee pain compared to general approaches.

OSTEOARTHRITIS: A PROGRESSIVE DISEASE WITH CHANGING PHENOTYPES.

I apologize, but I cannot provide a meaningful summary of this research paper because the abstract is listed as "NA" (not available).

To write an accurate summary focusing on the study objective, methods, findings about osteoarthritis phenotypes/subgroups, and implications for physiotherapy management, I would need access to the actual abstract content.

If you could provide the full abstract text, I would be happy to create a concise 3-4 sentence summary in plain language that addresses the specific areas you've requested regarding osteoarthritis phenotyping and musculoskeletal rehabilitation implications.

RELATIONSHIP BETWEEN KNEE PAIN AND THE PRESENCE, LOCATION, SIZE AND PHENOTYPE OF FEMOROTIBIAL DENUDED AREAS OF SUBCHONDRAL BONE AS VISUALIZED BY MRI.

This study aimed to investigate how denuded areas of subchondral bone (DABS) - regions where cartilage has worn away completely - relate to different types of knee pain in osteoarthritis. Researchers analyzed MRI scans from 633 participants, manually identifying areas of exposed bone and comparing pain patterns between people with and without DABS using various pain measures (weight-bearing, frequent, and moderate-to-severe pain).

The study identified distinct pain-related phenotypes: people with any DABS had 64% higher likelihood of frequent pain and 45% higher likelihood of moderate-to-severe pain compared to those without DABS. Crucially, DABS located in central, weight-bearing regions of the knee were most strongly associated with weight-bearing pain, especially when more than 10% of the central area was denuded (81% increased likelihood).

These findings suggest that the location and extent of cartilage loss may be more important than simply having cartilage damage, with central weight-bearing areas being particularly problematic for pain. For physiotherapy management, this indicates that patients with central cartilage loss may benefit from targeted interventions to reduce weight-bearing loads and modify movement patterns that stress these vulnerable regions.

DIFFERENCES IN STRUCTURAL AND PAIN PHENOTYPES IN THE SODIUM MONOIODOACETATE AND MENISCAL TRANSECTION MODELS OF OSTEOARTHRITIS.

This study aimed to compare two different rat models of knee osteoarthritis to help researchers choose the most appropriate model for testing treatments. The researchers induced arthritis using either meniscal transection (MNX, which mimics joint injury) or chemical injection (MIA), then measured joint damage and pain behaviors over time, including testing a steroid treatment.

The study identified two distinct disease phenotypes: the MNX model showed more inflammation, bone spur formation, and weight-bearing problems, while the MIA model caused more consistent widespread pain sensitivity. Both models developed cartilage damage at similar rates, but the MNX model had greater structural joint changes and responded better to steroid treatment.

These findings suggest that different osteoarthritis models represent different aspects of the human disease - one more structural/inflammatory and one more pain-focused. For physiotherapy research, this implies that treatment strategies may need to be tailored differently depending on whether patients present primarily with structural joint problems or widespread pain sensitivity.

DELETION OF THE TRANSFORMING GROWTH FACTOR Β RECEPTOR TYPE II GENE IN ARTICULAR CHONDROCYTES LEADS TO A PROGRESSIVE OSTEOARTHRITIS-LIKE PHENOTYPE IN MICE.

This study aimed to understand how TGFβ signaling affects cartilage health and osteoarthritis development by investigating whether specific enzymes (MMP13 and ADAMTS5) are key targets in this pathway. Researchers used genetically modified mice where the TGFβ receptor was deleted from cartilage cells, along with cell culture experiments and additional mouse models where MMP13 or ADAMTS5 genes were also removed. The key finding was that mice lacking TGFβ signaling developed progressive osteoarthritis-like changes, but this damage was significantly reduced when MMP13 or ADAMTS5 were also deleted, and treatment with an MMP13 inhibitor also slowed disease progression. These results suggest that targeting MMP13 and ADAMTS5 enzymes could be promising therapeutic approaches for osteoarthritis management, potentially informing future drug development and treatment strategies for patients with this condition.

EFFECT OF LOW-LEVEL LASER THERAPY ON METALLOPROTEINASE MMP-2 AND MMP-9 PRODUCTION AND PERCENTAGE OF COLLAGEN TYPES I AND III IN A PAPAIN CARTILAGE INJURY MODEL.

This study investigated whether low-level laser therapy (LLLT) could help repair cartilage damage in a rat model of osteoarthritis. Researchers used 60 rats divided into four groups: healthy controls, untreated injured rats, and two groups treated with different laser power levels (50mW and 100mW) after inducing cartilage damage with papain injections.

The key finding was that both laser treatments improved cartilage repair by reducing harmful collagen type III and increasing beneficial collagen type I, but the lower power laser (50mW) was more effective at reducing damaging enzyme MMP-9 after 21 days compared to the higher power treatment.

This suggests that different laser power settings may represent distinct treatment phenotypes, with lower power LLLT being superior for managing cartilage breakdown enzymes. For physiotherapy practice, this indicates that LLLT could be a valuable treatment option for osteoarthritis, but optimal dosing parameters (specifically lower power settings) are crucial for maximizing therapeutic benefits in cartilage repair.

AN OA PHENOTYPE MAY OBTAIN MAJOR BENEFIT FROM BONE-ACTING AGENTS.

This systematic review aimed to identify an osteoarthritis (OA) phenotype that would respond well to bone-acting medications by examining research from 1990-2013 on subchondral bone changes in OA. The researchers reviewed studies investigating various bone medications and used imaging techniques like bone density scans and scintigraphy to assess subchondral bone changes. The key finding was that while bone-acting drugs showed mixed results overall, a specific subgroup of postmenopausal women with high bone remodeling and/or low subchondral bone density appeared to benefit most from these treatments, particularly strontium ranelate which showed both structural and clinical improvements. For clinical management, this suggests that bone density scanning combined with scintigraphy could help identify OA patients who would benefit from bone-targeted therapies, allowing for more personalized treatment approaches rather than applying these medications broadly to all OA patients.

HOW MANY DIFFERENT TYPES OF FEMORA ARE THERE IN PRIMARY HIP OSTEOARTHRITIS? AN ACTIVE SHAPE MODELING STUDY.

This study aimed to identify different types of hip bone shapes in patients with severe hip osteoarthritis to better understand the variation in bone structure. Researchers used advanced computer modeling (Active Shape Modeling) to analyze X-rays and CT scans from 345 patients, then used statistical clustering to group patients with similar bone shapes together. The analysis revealed 10 distinct shape patterns that accounted for over 96% of the variation in hip bone structure, with each group showing different characteristics related to bone geometry and patient demographics. These findings could help improve hip replacement surgery by enabling better-fitted implants and more personalized surgical approaches, though the direct implications for physiotherapy and non-surgical management are less clear from this structural study.

PATIENTS WITH HIP OSTEOARTHRITIS HAVE A PHENOTYPE WITH HIGH BONE MASS AND LOW LEAN BODY MASS.

This study aimed to identify whether people with hip osteoarthritis have distinct body composition characteristics that might contribute to the development of the condition. The researchers used dual-energy X-ray absorptiometry (DEXA) scans to compare bone density, body mass index, and fat/lean muscle percentages between 62 hip osteoarthritis patients and 187 healthy controls.

The study found that both men and women with hip osteoarthritis shared a specific phenotype characterized by higher bone mineral density, higher BMI, greater percentage of fat mass, and importantly, lower percentage of lean muscle mass compared to healthy individuals. Men with hip osteoarthritis also showed larger skeletal size than controls.

These findings suggest that the combination of stiffer bones (from high bone density) and reduced muscle mass may create conditions that predispose individuals to hip osteoarthritis, as muscles normally help protect joints from excessive stress. For physiotherapy management, these results highlight the importance of strengthening programs to address the muscle mass deficits and weight management strategies to optimize the fat-to-lean mass ratio in patients with or at risk for hip osteoarthritis.

SIRT1 AND OSTEOARTHRITIS. COMMENTS ON THE PAPER BY GABAY ET AL.: "SIRT1-DEFICIENT MICE EXHIBIT AN ALTERED CARTILAGE PHENOTYPE", JOINT BONE SPINE 2013.

I apologize, but I cannot provide a meaningful summary of this research paper. The abstract is listed as "NA" (not available), and the title only indicates this is a commentary piece about SIRT1 and osteoarthritis, specifically discussing another study by Gabay et al. from 2013 that examined cartilage changes in SIRT1-deficient mice.

To provide the comprehensive summary you've requested covering study objectives, methods, phenotyping findings, and physiotherapy implications, I would need access to the actual abstract or full text content of this commentary paper.

If you could provide the abstract text, I would be happy to create the focused 3-4 sentence summary in plain language that addresses your specific requirements for osteoarthritis phenotyping and rehabilitation insights.

A GENE EXPRESSION STUDY OF NORMAL AND DAMAGED CARTILAGE IN ANTEROMEDIAL GONARTHROSIS, A PHENOTYPE OF OSTEOARTHRITIS.

This study aimed to identify genes and biological pathways involved in osteoarthritis progression by examining a specific knee OA pattern called anteromedial gonarthrosis (AMG). The researchers used gene expression analysis to compare damaged and undamaged cartilage samples taken from the same knee joint in nine patients undergoing knee replacement surgery. They found 754 genes with significantly different expression levels between damaged and healthy cartilage, with changes particularly affecting cell signaling, cartilage structure, and inflammation pathways, including several previously unknown OA-related genes. This research highlights that AMG represents a distinct OA subtype with specific molecular characteristics, suggesting that different OA phenotypes may require tailored treatment approaches and emphasizing the importance of considering cartilage location and damage patterns when developing physiotherapy interventions or other treatments.

REPLY TO THE COMMENT BY WENDLING ET AL. ON THE ARTICLE "SIRT1-DEFICIENT MICE EXHIBIT AN ALTERED CARTILAGE PHENOTYPE", JOINT BONE SPINE 2013;80:613-20.

I apologize, but I cannot provide a meaningful summary of this research paper. The document you've provided appears to be a reply/response to a comment rather than an original research article, and there is no abstract available to analyze.

Without the abstract or the content of the reply, I cannot determine:
- The study objectives
- Research methods used
- Findings about osteoarthritis phenotypes or subgroups
- Clinical implications for physiotherapy or management

To provide you with a proper summary focused on osteoarthritis phenotyping and rehabilitation implications, I would need access to either the full text of this reply or the abstract of the original research article it references (the SIRT1-deficient mice study from 2013).

CORR INSIGHTS(®): PATIENTS WITH HIP OSTEOARTHRITIS HAVE A PHENOTYPE WITH HIGH BONE MASS AND LOW LEAN BODY MASS.

I notice that the abstract is listed as "NA" (not available), which limits my ability to provide a comprehensive summary of this study. However, based on the title, I can offer some insights:

**Study Objective:** This study appears to investigate the body composition characteristics of patients with hip osteoarthritis, specifically examining bone mass and lean body mass as potential phenotypic markers.

**Key Methods:** Without the abstract, I cannot specify the exact methods used, though body composition studies typically involve imaging techniques like DEXA scans or similar assessments to measure bone density and muscle mass.

**Main Findings:** The title suggests researchers identified a distinct phenotype in hip osteoarthritis patients characterized by high bone mass combined with low lean body mass (reduced muscle mass).

**Clinical Implications:** This phenotyping finding could be important for physiotherapy management, as patients with low muscle mass may require targeted strengthening interventions, while the high bone mass component might influence exercise prescription and loading strategies.

To provide a more detailed and accurate summary, I would need access to the full abstract containing the specific methodology, sample size, detailed results, and authors' conclusions.

OPTIMAL TYPES OF EXERCISE FOR LOWER LIMB OSTEOARTHRITIS.

I apologize, but I cannot provide a meaningful summary of this research paper because the abstract is not available (marked as "NA").

To write an accurate summary focusing on the study objective, methods, findings about osteoarthritis phenotypes/subgroups, and physiotherapy implications, I would need access to the full abstract or paper content.

If you could provide the abstract text, I would be happy to create a concise 3-4 sentence summary in plain language covering the key points you've requested regarding optimal exercise types for lower limb osteoarthritis.

HMGB1-LPS COMPLEX PROMOTES TRANSFORMATION OF OSTEOARTHRITIS SYNOVIAL FIBROBLASTS TO A RHEUMATOID ARTHRITIS SYNOVIAL FIBROBLAST-LIKE PHENOTYPE.

This study investigated whether a complex of bacterial toxin (LPS) and inflammatory protein (HMGB1) can transform osteoarthritis joint cells into rheumatoid arthritis-like cells. Researchers exposed osteoarthritis synovial fibroblasts to the HMGB1-LPS complex for five cell generations in laboratory culture, then analyzed changes in cell behavior and tested their effects in mice. The transformed cells showed increased proliferation, reduced cell death, enhanced survival mechanisms, and gained the ability to invade and destroy cartilage when implanted in mice - characteristics typical of aggressive rheumatoid arthritis cells. These findings suggest that certain bacterial infections might trigger the transformation of osteoarthritis into a more destructive, rheumatoid arthritis-like condition, which could help explain why some osteoarthritis patients develop more severe inflammatory symptoms and may benefit from anti-inflammatory treatments typically used for rheumatoid arthritis.

HYPOXIA MODULATES THE PHENOTYPE OF OSTEOBLASTS ISOLATED FROM KNEE OSTEOARTHRITIS PATIENTS, LEADING TO UNDERMINERALIZED BONE NODULE FORMATION.

This study investigated how low oxygen levels (hypoxia) affect bone-forming cells (osteoblasts) from knee osteoarthritis patients to understand disease mechanisms. Researchers collected bone samples from knee replacement surgeries and cultured the isolated osteoblasts under normal and low oxygen conditions, then analyzed gene expression, enzyme activity, and bone formation capacity. The key finding was that hypoxia dramatically altered the osteoblast phenotype, causing these cells to produce weaker, poorly mineralized bone and increased inflammatory substances like PGE2, which differs significantly from healthy bone cells. These results suggest that poor oxygen supply in osteoarthritic joints may be a major driver of bone deterioration, potentially indicating that treatments targeting blood flow and oxygenation—through exercise, manual therapy, or other physiotherapy interventions that improve circulation—could be important for managing osteoarthritis progression.

GENOTYPE TO PHENOTYPE CORRELATIONS IN CARTILAGE OLIGOMERIC MATRIX PROTEIN ASSOCIATED CHONDRODYSPLASIAS.

This study aimed to establish clear relationships between specific genetic mutations in cartilage oligomeric matrix protein (COMP) and the resulting disease patterns in two related skeletal conditions - pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). The researchers analyzed 300 COMP mutations from multiple studies, including 25 newly identified mutations, to map which genetic changes lead to which disease type.

The analysis revealed that mutations in specific locations within the COMP protein are significantly associated with either PSACH or MED, establishing clear genotype-to-phenotype correlations for the first time. Both conditions cause short stature, joint pain and stiffness, and early-onset osteoarthritis, but the specific genetic mutation location can predict which form a patient will develop.

These findings could help clinicians predict disease severity and progression in patients with COMP mutations, potentially guiding more personalized treatment approaches and informing genetic counseling for affected families.

INDUCTION OF AN INFLAMMATORY AND PRODEGRADATIVE PHENOTYPE IN AUTOLOGOUS FIBROBLAST-LIKE SYNOVIOCYTES BY THE INFRAPATELLAR FAT PAD FROM PATIENTS WITH KNEE OSTEOARTHRITIS.

This study investigated whether the infrapatellar fat pad (IFP) - a fatty tissue inside the knee - contributes to joint inflammation in patients with severe knee osteoarthritis. Researchers collected tissue samples from 28 patients during knee replacement surgery and tested how substances released by the IFP affected nearby joint lining cells (synoviocytes) in laboratory conditions.

The results showed that the IFP triggered a strong inflammatory response in joint lining cells, causing them to produce high levels of inflammatory chemicals and enzymes that break down cartilage - this response was much stronger than what occurred with regular fat tissue from elsewhere in the body. Particularly, the IFP produced 75 times more of an inflammatory substance called PGE2, which appeared to drive much of the inflammatory reaction.

These findings suggest that in severe knee osteoarthritis, the infrapatellar fat pad develops a harmful inflammatory profile that may worsen joint damage and symptoms. For physiotherapy and management, this research highlights the IFP as a potential treatment target and suggests that interventions aimed at reducing inflammation in this specific tissue could be beneficial for patients with knee osteoarthritis.

CD4⁺CD25⁺/HIGHCD127LOW/⁻ REGULATORY T CELLS ARE ENRICHED IN RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS JOINTS--ANALYSIS OF FREQUENCY AND PHENOTYPE IN SYNOVIAL MEMBRANE, SYNOVIAL FLUID AND PERIPHERAL BLOOD.

This study aimed to compare the distribution and characteristics of regulatory T cells (Tregs) - immune cells that help control inflammation - in joint tissues, joint fluid, and blood samples from patients with rheumatoid arthritis (RA) versus osteoarthritis (OA). The researchers used flow cytometry to analyze samples from 40 patients (18 RA, 22 OA) and examined various cell surface markers to assess Treg function and activation status.

Key findings revealed that Tregs accumulate in both RA and OA joints at similar relative frequencies, but RA patients had significantly higher absolute concentrations of Tregs in joint tissue, challenging the idea that RA results from Treg deficiency. The study identified two distinct Treg phenotypes: synovial (joint) Tregs were activated memory cells, while peripheral blood Tregs were resting memory cells.

These findings suggest that both inflammatory (RA) and degenerative (OA) joint diseases involve similar immune regulatory responses, which may influence how physiotherapists and clinicians approach treatment strategies, potentially supporting more individualized management approaches rather than assuming fundamentally different immune profiles between these conditions.

QUANTITATIVE X-RAY MICRORADIOGRAPHY FOR HIGH-THROUGHPUT PHENOTYPING OF OSTEOARTHRITIS IN MICE.

This study aimed to develop and validate digital X-ray microradiography as a fast, affordable screening method to identify different joint disease patterns in mice with osteoarthritis. Researchers used this imaging technique to measure bone mineral content in the subchondral bone (bone just under cartilage) of mouse knee joints, testing it in both surgically-induced arthritis models and genetically modified mice with bone abnormalities. The method successfully detected increased bone mineral content in mice with osteoarthritis, showing high precision (3.6% variation) and ability to distinguish different disease phenotypes in both male and female mice at various time points. While this is a preclinical animal study, the validated screening approach could help researchers better understand different osteoarthritis subtypes, which may eventually inform more targeted physiotherapy and management strategies for patients with varying bone and joint characteristics.

THE RELATIVE CONTRIBUTION OF MECHANICAL STRESS AND SYSTEMIC PROCESSES IN DIFFERENT TYPES OF OSTEOARTHRITIS: THE NEO STUDY.

This study aimed to understand whether mechanical stress (like body weight) or systemic processes (like metabolic problems) are more important risk factors for osteoarthritis in different joint locations. Researchers analyzed data from 6,673 Dutch adults aged 45-65, measuring body composition and metabolic health, then using statistical models to compare osteoarthritis patterns in knees only, hands only, or both locations.

The study identified three distinct osteoarthritis phenotypes: knee-only OA (10% of participants) was primarily linked to mechanical factors like higher body weight and muscle mass, hand-only OA (8%) was mainly associated with metabolic syndrome, while combined knee-and-hand OA (4%) showed similar mechanical stress patterns to knee-only disease.

These findings suggest that different osteoarthritis phenotypes have different underlying causes, which has important implications for physiotherapy and management - knee OA patients may benefit most from weight management and mechanical load reduction strategies, while hand OA patients might need interventions targeting metabolic health alongside joint-specific treatments.

CELLULAR SENESCENCE AND THE SENESCENT SECRETORY PHENOTYPE IN AGE-RELATED CHRONIC DISEASES.

This review study aimed to examine how cellular senescence and the senescence-associated secretory phenotype (SASP) contribute to chronic inflammation in age-related diseases. The authors analyzed existing research on SASP mechanisms and their role in promoting inflammatory conditions including osteoarthritis, atherosclerosis, Alzheimer's disease, type 2 diabetes, and cancers. The key finding is that senescent cells appear to drive a state of chronic, low-grade "sterile" inflammation that underlies multiple age-related disorders, with the SASP serving as a key mechanism linking cellular aging to disease development. Understanding this senescence-inflammation connection could lead to new diagnostic approaches and therapeutic targets, potentially including interventions that target senescent cells or their inflammatory secretions, which may be relevant for developing anti-aging strategies in musculoskeletal rehabilitation and osteoarthritis management.

BAICALEIN AMELIORATES INFLAMMATORY-RELATED APOPTOTIC AND CATABOLIC PHENOTYPES IN HUMAN CHONDROCYTES.

This laboratory study investigated whether baicalein (a natural compound) could protect cartilage cells from the damaging effects of inflammation in osteoarthritis. Researchers exposed human cartilage cells to inflammatory molecules (IL-1β and TNF-α) and tested baicalein's protective effects using cell culture experiments and cartilage tissue samples. The study found that baicalein reduced two harmful processes in cartilage cells: it prevented cell death (apoptosis) by blocking nitric oxide production, and it reduced the release of enzymes (MMPs) that break down cartilage matrix. These findings suggest that baicalein could potentially be developed as a treatment to slow cartilage breakdown in osteoarthritis, though clinical trials would be needed to determine if this translates to benefits for patients receiving physiotherapy or other treatments.

CARDIOVASCULAR MANIFESTATIONS IN MARFAN SYNDROME AND RELATED DISEASES; MULTIPLE GENES CAUSING SIMILAR PHENOTYPES.

This study aimed to review the cardiovascular manifestations and underlying molecular mechanisms in Marfan syndrome and related connective tissue disorders that share similar clinical features. The researchers examined clinical and experimental evidence linking these conditions through dysregulated transforming growth factor β (TGFβ) signaling pathways. The key finding is that while Marfan syndrome results from mutations in extracellular matrix proteins, related conditions like Loeys-Dietz syndrome and aneurysm-osteoarthritis syndrome are caused by defects in TGFβ pathway components, yet all produce similar cardiovascular phenotypes through this common signaling disruption. These insights suggest that TGFβ antagonism could be a promising therapeutic target for managing these conditions, though the authors emphasize that more research is needed before this approach can be safely applied to patient care.

F-SPONDIN DEFICIENT MICE HAVE A HIGH BONE MASS PHENOTYPE.

This study aimed to understand the role of F-spondin (a protein found in cartilage) by examining mice that were genetically modified to lack this protein. The researchers used microscopic analysis, CT scans, and blood tests to compare bone and cartilage characteristics between normal mice and those missing the F-spondin gene over 6-12 months.

The key finding was that mice without F-spondin developed a distinct "high bone mass" phenotype, meaning they had denser, thicker bones than normal mice, while their joint cartilage remained relatively normal. The researchers discovered this occurred through changes in bone-building signals, with reduced TGF-β and increased BMP signaling leading to greater bone formation.

These findings suggest that F-spondin normally acts as a "brake" on bone formation, and its absence in osteoarthritis patients might contribute to abnormal bone changes seen in the condition, potentially informing future targeted treatments for managing bone-related aspects of joint disease.

NANOMECHANICAL PHENOTYPE OF CHONDROADHERIN-NULL MURINE ARTICULAR CARTILAGE.

This study investigated how deleting the chondroadherin (CHAD) protein affects the mechanical properties of joint cartilage in mice. Researchers used atomic force microscopy to measure the stiffness and mechanical behavior of cartilage at the nanoscale level in mice with and without the CHAD protein across different ages.

The key finding was that mice lacking CHAD showed a dramatic 70-80% reduction in cartilage stiffness in the surface layer of knee cartilage, along with abnormal collagen fiber structure, while deeper cartilage layers remained unaffected. Importantly, these significant mechanical changes occurred without obvious visual changes in cartilage appearance under standard microscopic examination.

This research identifies a distinct mechanical phenotype of cartilage that could be missed by conventional assessment methods, highlighting how genetic factors can create "hidden" cartilage weaknesses. For physiotherapy practice, this suggests that some patients may have cartilage that appears normal but has compromised mechanical properties, potentially requiring modified exercise programs or loading strategies to prevent further joint damage.

EXPRESSION OF RECEPTORS OF ADVANCED GLYCATION END PRODUCT (RAGE) AND TYPES I, III AND IV COLLAGEN IN THE VASTUS LATERALIS MUSCLE OF MEN IN EARLY STAGES OF KNEE OSTEOARTHRITIS.

This study investigated muscle protein changes in men with early-stage knee osteoarthritis by examining collagen types and receptors for advanced glycation end products (RAGE) in thigh muscle biopsies. The researchers compared muscle samples from 18 men with early knee osteoarthritis to 17 healthy controls using specialized staining techniques to measure protein expression. The key finding was that men with osteoarthritis showed increased levels of all collagen types (particularly types III and IV) in their muscle tissue, but no differences in RAGE receptor expression compared to healthy men. These results suggest that even in early osteoarthritis, the thigh muscles undergo structural changes that may represent protective adaptations to maintain muscle flexibility and prevent injury, which could inform physiotherapy approaches focused on preserving muscle quality alongside traditional strengthening exercises.

CANINE HIP DYSPLASIA: PHENOTYPIC SCORING AND THE ROLE OF ESTIMATED BREEDING VALUE ANALYSIS.

This study aimed to review methods for identifying and scoring canine hip dysplasia (CHD) to improve breeding selection and reduce disease prevalence. The researchers examined traditional radiographic scoring methods that assess joint structure and newer techniques that measure joint laxity (looseness), along with estimated breeding value (EBV) analysis that considers genetic information from both individual dogs and their relatives. The study found that traditional scoring methods have shown variable success in reducing CHD prevalence, with the best results occurring when scoring is mandatory and breeding records are openly accessible, while EBV analysis may provide superior breeding selection by better predicting genetic merit. These findings suggest that combining improved joint assessment techniques with genetic analysis could enhance breeding programs and potentially inform rehabilitation strategies, though this veterinary research has limited direct application to human osteoarthritis management.

MAJOR INTERCONTINENTALLY DISTRIBUTED SEQUENCE TYPES OF KINGELLA KINGAE AND DEVELOPMENT OF A RAPID MOLECULAR TYPING TOOL.

This study appears to be about bacterial genetics rather than osteoarthritis phenotyping, so it falls outside my specialization area. The research investigated the genetic diversity of Kingella kingae bacteria, which causes bone and joint infections in young children, by analyzing 324 bacterial strains from multiple continents using molecular typing methods. The researchers identified distinct bacterial subtypes (sequence types) and found that five major groups were distributed worldwide, with some strains showing optimal fitness characteristics. While this work could inform infection management in pediatric cases, it doesn't directly relate to osteoarthritis phenotyping or musculoskeletal rehabilitation approaches that would typically guide physiotherapy interventions.

PAIN PHENOTYPE IN PATIENTS WITH KNEE OSTEOARTHRITIS: CLASSIFICATION AND MEASUREMENT PROPERTIES OF PAINDETECT AND SELF-REPORT LEEDS ASSESSMENT OF NEUROPATHIC SYMPTOMS AND SIGNS SCALE IN A CROSS-SECTIONAL STUDY.

This study aimed to evaluate two questionnaires (painDETECT and S-LANSS) for identifying different pain types in 192 knee osteoarthritis patients, and tested their ability to detect abnormal central pain processing using quantitative sensory testing in 77 patients. The researchers found that painDETECT had better measurement properties than S-LANSS, and patients with higher painDETECT scores showed widespread increased pain sensitivity, suggesting problems with how the central nervous system processes pain signals. The two questionnaires showed poor agreement in classifying patients into pain subgroups, indicating they may be measuring different aspects of the pain experience. These findings suggest that painDETECT could help physiotherapists identify osteoarthritis patients with central pain sensitization, who may need different treatment approaches than those with more typical joint-related pain, though more research is needed to determine which tool best predicts treatment success.

MELANOCORTIN 1 RECEPTOR-SIGNALING DEFICIENCY RESULTS IN AN ARTICULAR CARTILAGE PHENOTYPE AND ACCELERATES PATHOGENESIS OF SURGICALLY INDUCED MURINE OSTEOARTHRITIS.

This study investigated how deficiency in melanocortin 1 receptor (MC1R) signaling affects joint health and osteoarthritis development using genetically modified mice. Researchers compared MC1R-deficient mice to normal mice, examining cartilage and bone changes both naturally and after surgically inducing osteoarthritis, using imaging techniques and tissue staining methods.

The key finding was that MC1R-deficient mice had a distinct joint phenotype characterized by smaller cartilage areas and reduced cartilage matrix proteins even before developing osteoarthritis. When osteoarthritis was surgically induced, these mice developed more severe disease with increased cartilage breakdown, more bone spurs (osteophytes), and denser subchondral bone compared to normal mice.

These results suggest that MC1R signaling plays a protective role in maintaining healthy cartilage and preventing excessive bone changes in osteoarthritis, indicating that some patients may have genetic variations affecting this pathway that make them more susceptible to severe joint degeneration and potentially requiring more intensive physiotherapy interventions.

LOW-FREQUENCY HIGH-MAGNITUDE MECHANICAL STRAIN OF ARTICULAR CHONDROCYTES ACTIVATES P38 MAPK AND INDUCES PHENOTYPIC CHANGES ASSOCIATED WITH OSTEOARTHRITIS AND PAIN.

This laboratory study investigated how excessive mechanical stress on cartilage cells (chondrocytes) contributes to osteoarthritis development and pain. Researchers applied high-magnitude mechanical strain to cartilage cells grown on flexible membranes and measured changes in gene expression, protein activity, and factors released by the cells. The study found that mechanically stressed cartilage cells developed an inflammatory, degenerative phenotype characterized by increased production of nerve growth factor, inflammatory molecules (TNFα), and cartilage-degrading enzymes (ADAMTS4), while also activating pain-related cellular pathways (p38 MAPK). These findings suggest that protecting joints from excessive mechanical loading may be crucial in physiotherapy management, as high-impact or repetitive loading could potentially worsen cartilage breakdown and pain in osteoarthritis patients.

PATIENTS WITH KNEE OSTEOARTHRITIS HAVE A PHENOTYPE WITH HIGHER BONE MASS, HIGHER FAT MASS, AND LOWER LEAN BODY MASS.

This study aimed to identify the body composition and bone characteristics (phenotype) of people with knee osteoarthritis compared to healthy controls. The researchers used dual-energy X-ray absorptiometry (DEXA) scans to measure bone density, body mass index, and fat/muscle proportions in 112 knee OA patients versus 243 controls. They found that both men and women with knee OA had a distinct phenotype characterized by higher bone density, higher BMI, proportionally more fat mass, and proportionally less lean muscle mass compared to healthy individuals. These findings suggest that physiotherapy and management approaches for knee OA should prioritize weight management and muscle strengthening exercises, as the combination of excess weight, reduced muscle mass, and stiffer bones may create a cycle that worsens joint loading and reduces the knee's natural protection.

MECHANOSTIMULATION CHANGES THE CATABOLIC PHENOTYPE OF HUMAN DEDIFFERENTIATED OSTEOARTHRITIC CHONDROCYTES.

This study investigated whether mechanical stimulation could improve the quality of cartilage cells from osteoarthritis patients for use in cartilage repair treatments. Researchers took cartilage cells from 9 knee replacement patients, embedded them in a collagen gel, and applied gentle cyclic compression (1 Hz frequency, 2.5% compression) for 4 days using an intermittent schedule (1 hour stimulation, 4 hour rest).

The mechanical stimulation dramatically improved the cellular phenotype, with cells producing more cartilage-building proteins (collagen II increased significantly, aggrecan increased) and fewer cartilage-destroying enzymes (MMP-13 decreased significantly), while also tripling the production of key cartilage components and returning to their normal rounded shape.

These findings suggest that even damaged cartilage cells from osteoarthritis patients can be "rehabilitated" through appropriate mechanical loading, potentially expanding the pool of patients eligible for cartilage repair procedures. For physiotherapy practice, this supports the importance of incorporating moderate, dynamic compression exercises in rehabilitation programs following cartilage repair surgeries to optimize healing outcomes.

ACQUIRING CHONDROCYTE PHENOTYPE FROM HUMAN MESENCHYMAL STEM CELLS UNDER INFLAMMATORY CONDITIONS.

This study aimed to review how human mesenchymal stem cells (MSCs) can develop into cartilage-forming cells (chondrocytes) in inflammatory conditions typical of joint diseases like osteoarthritis and rheumatoid arthritis. The researchers conducted a systematic literature search and identified nine relevant studies examining how inflammatory signals affect the ability of human MSCs to become chondrocytes. The review revealed that while inflammation typically destroys cartilage and kills existing cartilage cells, MSCs present in cartilage tissue may still be able to differentiate into new chondrocytes even under these harsh inflammatory conditions. These findings suggest that MSC-based therapies could potentially help repair irreversible cartilage damage in patients with degenerative joint diseases, though the authors note that the effectiveness and exact mechanisms of such treatments require further investigation before widespread clinical application.

PATIENTS WITH OSTEOARTHRITIS IN ALL THREE KNEE COMPARTMENTS AND PATIENTS WITH MEDIAL KNEE OSTEOARTHRITIS HAVE A PHENOTYPE WITH HIGH BONE MASS AND HIGH FAT MASS BUT PROPORTIONALLY LOW LEAN MASS.

This study aimed to determine whether knee osteoarthritis (OA) patients have a similar body composition phenotype to hip OA patients, specifically examining bone density and body composition patterns. The researchers compared body composition measurements using DEXA scans between 112 people with knee OA (either affecting all three knee compartments or just the medial compartment) and 243 healthy controls.

Both knee OA groups showed a distinct phenotype characterized by higher bone density, higher BMI, increased fat mass, but proportionally less lean (muscle) mass compared to people without arthritis. This pattern was consistent whether patients had arthritis in all knee compartments or just the medial (inner) compartment, suggesting this body composition profile is a common feature across different types of knee OA.

These findings have important implications for physiotherapy management, as the combination of excess weight, higher fat mass, and relatively low muscle mass may contribute to joint loading problems and functional limitations, highlighting the need for targeted interventions focusing on weight management and muscle strengthening in knee OA patients.

CLASSIFICATION OF OSTEOARTHRITIS PHENOTYPES BY METABOLOMICS ANALYSIS.

This study aimed to identify metabolic markers in synovial fluid that could classify osteoarthritis (OA) patients into distinct subgroups. The researchers analyzed synovial fluid samples from 80 patients (38 men, 42 women) undergoing knee or hip replacement surgery using targeted metabolomics, examining various metabolites while controlling for age, sex, BMI, and comorbidities. The analysis revealed two main patient groups with distinct metabolic profiles: Group A showed significantly higher levels of 37 out of 39 acylcarnitines but lower free carnitine, while Group B (further divided into B1 and B2 subgroups) was characterized by differences in 86 metabolites including glycerophospholipids and sphingolipids, suggesting involvement of carnitine, lipid, and collagen metabolism pathways. These findings indicate that OA consists of metabolically distinct subgroups that could potentially guide the development of targeted therapies and personalized treatment approaches, though the clinical implications for physiotherapy management require further investigation.

INTRA- AND INTEROBSERVER AGREEMENT ON RADIOGRAPHIC PHENOTYPE IN THE DIAGNOSIS OF CANINE HIP DYSPLASIA.

This study examined how consistently different groups of veterinary experts could identify specific bone changes (phenotypes) on hip X-rays when diagnosing canine hip dysplasia. The researchers had 50 hip X-rays evaluated by 9 experienced observers from three groups (surgeons, radiologists, and non-board certified practitioners) who looked for specific features like bone spurs and joint degeneration. The study found that agreement between observers was only fair to moderate, with radiologists and non-board certified observers showing more consistent scoring than surgeons for most features, and academic observers being more consistent than non-academic ones. These findings suggest that even experienced professionals have difficulty reliably identifying these radiographic phenotypes, which has important implications for screening programs and treatment decisions, highlighting the need for standardized training and potentially more objective assessment methods.

DECONSTRUCTING THE ANTERIOR CRUCIATE LIGAMENT: WHAT WE KNOW AND DO NOT KNOW ABOUT FUNCTION, MATERIAL PROPERTIES, AND INJURY MECHANICS.

This review aimed to identify knowledge gaps in anterior cruciate ligament (ACL) research that contribute to persistent injury rates, sex-based disparities, and long-term complications like osteoarthritis. The authors analyzed five decades of literature examining ACL structure, mechanics, and injury patterns to pinpoint critical research limitations. They identified three major gaps: lack of data on ACL mechanics under actual injury-level loading rates, oversimplified mechanical testing that doesn't capture the ligament's complex 3D behavior, and use of reconstruction grafts that are too stiff compared to native tissue. These limitations result in increased reinjury risk and altered knee joint mechanics that may predispose patients to osteoarthritis, suggesting that improved understanding of ACL biomechanics could lead to better surgical techniques and rehabilitation strategies to preserve long-term joint health.

SOLUBLE MACROPHAGE BIOMARKERS INDICATE INFLAMMATORY PHENOTYPES IN PATIENTS WITH KNEE OSTEOARTHRITIS.

This study aimed to determine whether macrophage biomarkers (CD163 and CD14) could identify different inflammatory phenotypes in knee osteoarthritis patients. The researchers analyzed blood and synovial fluid samples from 184 patients across two cohorts, using statistical models to examine relationships between these biomarkers and joint inflammation, structural damage, and pain levels.

The key finding was that higher levels of CD14 and CD163 in synovial fluid were associated with more activated macrophages in the joint, greater structural damage (joint space narrowing and bone spurs), faster disease progression, and increased pain severity. This suggests that patients can be classified into inflammatory versus non-inflammatory phenotypes based on these biomarker levels.

For physiotherapy and clinical management, these biomarkers could help identify patients with active inflammatory osteoarthritis who may have worse outcomes and need more intensive or targeted treatments, potentially allowing for more personalized rehabilitation approaches.

CARTILAGE-SPECIFIC DELETION OF EPHRIN-B2 IN MICE RESULTS IN EARLY DEVELOPMENTAL DEFECTS AND AN OSTEOARTHRITIS-LIKE PHENOTYPE DURING AGING IN VIVO.

This study aimed to investigate the role of ephrin-B2 (EFNB2) protein in skeletal development and osteoarthritis using genetically modified mice where EFNB2 was specifically removed from cartilage cells. Researchers used comprehensive imaging and tissue analysis techniques to examine mice from birth through one year of age, comparing normal mice to those lacking cartilage EFNB2.

The study revealed that mice without cartilage EFNB2 showed significant developmental problems including smaller size, disorganized growth plates, delayed bone formation, and reduced bone density throughout their skeletons. As these mice aged to one year old, they developed osteoarthritis-like changes in both knee and hip joints, and about 27% also developed movement problems due to spinal cord abnormalities.

These findings suggest that EFNB2 deficiency may represent a specific osteoarthritis phenotype characterized by both joint degeneration and underlying bone/cartilage developmental abnormalities. For physiotherapy and management, this research indicates that patients with early-onset or severe osteoarthritis might benefit from comprehensive assessment of bone health and neurological function, not just joint-focused treatments.

CD271(+) STROMAL CELLS EXPAND IN ARTHRITIC SYNOVIUM AND EXHIBIT A PROINFLAMMATORY PHENOTYPE.

This study aimed to investigate the distribution and functional properties of CD271(+) stromal cells in joint tissues from patients with rheumatoid arthritis (RA), osteoarthritis (OA), and healthy controls. The researchers used tissue analysis, cell sorting techniques, and laboratory experiments to compare the inflammatory and immune-regulating behaviors of CD271(+) versus CD271(-) cells.

The key finding was that CD271(+) stromal cells were more abundant in arthritic joints (both RA and OA) compared to healthy tissue, and these cells exhibited a distinctly pro-inflammatory phenotype. Specifically, CD271(+) cells from OA joints produced significantly higher levels of inflammatory molecules (IL-6) and tissue-damaging enzymes (MMP-1 and MMP-3) compared to CD271(-) cells.

These findings suggest that CD271(+) stromal cells may represent a specific inflammatory subgroup that contributes to joint damage in arthritis. For physiotherapy and rehabilitation, this research highlights the importance of targeting inflammation in treatment approaches, and suggests that future therapies might need to specifically address these pro-inflammatory cell populations to more effectively manage osteoarthritis progression.

OA PHENOTYPES, RATHER THAN DISEASE STAGE, DRIVE STRUCTURAL PROGRESSION--IDENTIFICATION OF STRUCTURAL PROGRESSORS FROM 2 PHASE III RANDOMIZED CLINICAL STUDIES WITH SYMPTOMATIC KNEE OA.

This study aimed to identify key characteristics that predict structural progression in knee osteoarthritis by analyzing data from over 2,200 patients followed for two years in clinical trials. Researchers examined relationships between radiographic progression and baseline factors including joint space width, disease severity (KL grade), pain scores, and BMI using post-hoc analysis of two large randomized controlled trials.

The key finding was that patient phenotypes (specific characteristic patterns) rather than disease stage drive structural progression, with only about half of patients showing meaningful structural worsening over two years. While BMI, disease severity, and pain levels were all associated with having osteoarthritis, only disease severity (KL grade) and pain levels could predict future progression, though pain showed a complex non-linear relationship.

These results suggest that physiotherapists and clinicians should focus on identifying patients with "progressor phenotypes" rather than treating all osteoarthritis patients the same way, as nearly half of patients may not experience significant structural worsening and might benefit from different management approaches tailored to their specific characteristics.

CLINICAL PHENOTYPES IN PATIENTS WITH KNEE OSTEOARTHRITIS: A STUDY IN THE AMSTERDAM OSTEOARTHRITIS COHORT.

This study aimed to identify and validate distinct clinical phenotypes (subgroups) of knee osteoarthritis patients using data from 551 participants in the Amsterdam Osteoarthritis cohort. Researchers used cluster analysis to group patients based on four key characteristics: muscle strength, body mass index, X-ray severity, and depressive symptoms. Five distinct phenotypes were identified: minimal joint disease, strong muscle strength, severe radiographic changes, obesity-related, and depression-related groups, which closely matched patterns found in previous research. These validated phenotypes suggest that knee osteoarthritis patients have different underlying disease patterns, which could help physiotherapists and clinicians tailor treatments more specifically - for example, focusing on weight management for the obese phenotype, strength training for those with weak muscles, or addressing mental health alongside physical symptoms for the depressive mood phenotype.

INDIVIDUALS WITH PRIMARY OSTEOARTHRITIS HAVE DIFFERENT PHENOTYPES DEPENDING ON THE AFFECTED JOINT - A CASE CONTROL STUDY FROM SOUTHERN SWEDEN INCLUDING 514 PARTICIPANTS.

This study aimed to determine whether people with primary osteoarthritis (OA) in different joints have distinct physical characteristics compared to healthy controls. The researchers compared body composition measurements (bone density, fat mass, lean mass, BMI) in 274 OA patients (affecting hip, knee, ankle/foot, or hand joints) against 240 healthy controls using specialized X-ray scans.

The key finding was that OA patients could be grouped into two distinct phenotypes: those with lower limb OA (hip, knee, ankle/foot) had higher bone density, higher BMI, more body fat, and less muscle mass compared to healthy controls, while hand OA patients had similar body composition to healthy people. This suggests that lower limb OA and hand OA may develop through different disease processes.

These findings have important implications for physiotherapy and management, as they suggest that people with lower limb OA may particularly benefit from interventions targeting weight management, muscle strengthening, and body composition optimization, while hand OA may require different treatment approaches.

PHENOMEEXPRESS: A REFINED NETWORK ANALYSIS OF EXPRESSION DATASETS BY INCLUSION OF KNOWN DISEASE PHENOTYPES.

This study developed PhenomeExpress, a new computational method to analyze gene expression data by combining protein interaction networks with known disease characteristics to better identify disease mechanisms. The researchers tested their approach using two case studies - subchondral bone changes in osteoarthritis and a type of leukemia - and compared it against existing analysis methods using both mouse and human datasets. The method successfully identified core disease pathways and enhanced detection of molecular disease patterns (phenotypes) by incorporating relevant disease information rather than relying solely on general protein interaction data. For osteoarthritis management, this approach could help identify distinct molecular subgroups of patients and guide more targeted physiotherapy interventions by better understanding the underlying bone and joint tissue changes driving different disease presentations.

CAN WE IDENTIFY PATIENTS WITH HIGH RISK OF OSTEOARTHRITIS PROGRESSION WHO WILL RESPOND TO TREATMENT? A FOCUS ON EPIDEMIOLOGY AND PHENOTYPE OF OSTEOARTHRITIS.

This European working meeting aimed to identify different patient profiles in osteoarthritis to better predict disease progression and treatment response. The researchers analyzed various risk factors including systemic factors (age, sex, obesity, genetics) and local biomechanical factors (joint injury, muscle weakness, malalignment), with joint injury, malalignment, and synovitis being key predictors of progression.

The study identified several distinct osteoarthritis phenotypes: generalized/polyarticular disease (often linked to inflammation or metabolic syndrome) versus localized/monoarticular disease (typically post-traumatic with severe malalignment), early-stage versus late-stage disease profiles, and subgroups based on subchondral bone lesion patterns. Additional biomechanical profiles were defined by factors like joint malalignment, meniscal loss, and ligament injury.

These findings suggest that personalized osteoarthritis management should consider the patient's specific clinical presentation, underlying disease mechanisms, and disease stage, potentially leading to more targeted and effective treatments including specialized physiotherapy approaches for different phenotypic subgroups.

TARGETED DELETION OF COLLAGEN V IN TENDONS AND LIGAMENTS RESULTS IN A CLASSIC EHLERS-DANLOS SYNDROME JOINT PHENOTYPE.

This study aimed to understand how collagen V deficiency in tendons and ligaments contributes to the joint problems seen in classic Ehlers-Danlos syndrome. Researchers used genetically modified mice that lacked collagen V specifically in their tendons and ligaments, then examined the structural and functional changes that occurred. The mice developed key features resembling Ehlers-Danlos syndrome, including joint looseness, weakness, abnormal movement patterns, and early arthritis, with more severe changes occurring in major joint-stabilizing ligaments (like the ACL) compared to smaller tendons. These findings suggest that people with Ehlers-Danlos syndrome may have different degrees of tissue damage throughout their body, indicating that physiotherapy and management strategies should be tailored based on which joints and structures are most affected, with particular attention to major weight-bearing and stabilizing structures.

DECONSTRUCTING CHRONIC LOW BACK PAIN IN THE OLDER ADULT--STEP BY STEP EVIDENCE AND EXPERT-BASED RECOMMENDATIONS FOR EVALUATION AND TREATMENT: PART I: HIP OSTEOARTHRITIS.

This study aimed to develop evidence-based recommendations for evaluating and treating hip osteoarthritis as a contributing factor to chronic low back pain in older adults. The researchers used a modified Delphi approach with expert panels to create evaluation and treatment algorithms specifically designed for healthcare settings. The key finding was that hip osteoarthritis represents an important but often overlooked contributor to chronic low back pain in older adults, forming part of what they termed "hip-spine syndrome" where multiple factors combine to cause pain and disability. The implications for physiotherapy and management are that clinicians should routinely screen older adults with chronic low back pain for hip osteoarthritis to ensure treatment targets all contributing factors rather than focusing solely on the spine.

INTRODUCTION TO SPECIAL SERIES: DECONSTRUCTING CHRONIC LOW BACK PAIN IN THE OLDER ADULT: SHIFTING THE PARADIGM FROM THE SPINE TO THE PERSON.

I apologize, but I cannot provide a meaningful summary of this research paper because the abstract is not available (marked as "NA").

While the title suggests this is an introductory piece for a special series focused on shifting from spine-centered to person-centered approaches for chronic low back pain in older adults, I cannot determine the specific study objectives, methods, findings about patient subgroups, or clinical implications without access to the abstract content.

To provide an accurate summary addressing the phenotyping, rehabilitation methods, patient subgroups, and physiotherapy implications you've requested, I would need the actual abstract text.

THE EFFECT OF DIFFERENT TYPES OF INSOLES OR SHOE MODIFICATIONS ON MEDIAL LOADING OF THE KNEE IN PERSONS WITH MEDIAL KNEE OSTEOARTHRITIS: A RANDOMISED TRIAL.

This randomized trial investigated how different shoe modifications affect knee loading and symptoms in 70 people with medial knee osteoarthritis. Participants underwent gait analysis while walking in five conditions: barefoot, control shoe, two types of lateral wedge insoles, and a mobility shoe, with pain and comfort assessed simultaneously.

The study found that lateral wedge insoles (both types) and barefoot walking effectively reduced harmful knee loading forces compared to regular shoes, while the mobility shoe provided significant pain relief and improved comfort but didn't reduce knee loading.

These findings suggest that different shoe interventions may benefit different patient subgroups - those needing biomechanical improvements might benefit from lateral wedge insoles, while those prioritizing immediate pain relief might prefer mobility shoes, indicating the importance of personalized footwear recommendations in knee osteoarthritis management.

CLINICAL PHENOTYPE CLASSIFICATIONS BASED ON STATIC VARUS ALIGNMENT AND VARUS THRUST IN JAPANESE PATIENTS WITH MEDIAL KNEE OSTEOARTHRITIS.

This study aimed to examine how different knee alignment patterns relate to walking pain in Japanese patients with medial knee osteoarthritis. Researchers classified 266 patients into four groups based on whether they had static varus alignment (knock-knee positioning at rest) and/or varus thrust (sudden inward knee movement during walking), then used statistical analysis to compare pain levels between groups.

The key finding was that patients with varus thrust experienced significantly more knee pain during walking, with the highest pain levels occurring in those who had both varus thrust and static varus alignment (17 times higher odds of walking pain). Even patients with varus thrust alone had over 3 times higher odds of experiencing walking pain compared to those without these alignment issues.

These results suggest that physiotherapists and clinicians should assess both static knee alignment and dynamic movement patterns during walking, as patients with varus thrust may benefit from targeted interventions to address this movement dysfunction and reduce walking-related pain.

DIFFERENTIATION OF OSTEOPHYTE TYPES IN OSTEOARTHRITIS - PROPOSAL OF A HISTOLOGICAL CLASSIFICATION.

This study aimed to develop a standardized classification system for osteophytes (bony outgrowths) in osteoarthritis to improve research consistency. Researchers analyzed 94 osteophytes from 10 knee replacement patients using detailed tissue staining techniques to examine their structure and composition. They identified four distinct osteophyte types based on how much bone formation had occurred and the amount of connective tissue present, with these types appearing regardless of osteophyte size or location in the joint. This classification system could help researchers and clinicians better understand osteophyte development and potentially guide more targeted treatment approaches, though the study doesn't directly address specific physiotherapy implications.

HYPOXIA-INDUCIBLE FACTOR 3-ALPHA EXPRESSION IS ASSOCIATED WITH THE STABLE CHONDROCYTE PHENOTYPE.

This study investigated the role of HIF-3α (a protein that responds to low oxygen levels) in cartilage cells and its relationship to different cell states in healthy and osteoarthritic cartilage. Researchers examined HIF-3α expression in laboratory-grown stem cells and cartilage cells, as well as in human embryonic and adult cartilage tissues, measuring it alongside markers that indicate unhealthy, degenerative cartilage cells. The key finding was that HIF-3α levels were consistently higher in healthy, stable cartilage cells and lower in degenerative cells that produce enzymes and proteins associated with cartilage breakdown - this pattern was seen in osteoarthritic cartilage, stem cells developing into cartilage, and in the breakdown zones of developing embryonic cartilage. These results suggest that HIF-3α could serve as a biomarker to identify different cartilage cell phenotypes, potentially helping clinicians better classify osteoarthritis subtypes and develop more targeted rehabilitation strategies that support the maintenance of healthy cartilage cell function.

PRENATAL ETHANOL EXPOSURE INDUCES THE OSTEOARTHRITIS-LIKE PHENOTYPE IN FEMALE ADULT OFFSPRING RATS WITH A POST-WEANING HIGH-FAT DIET AND ITS INTRAUTERINE PROGRAMMING MECHANISMS OF CHOLESTEROL METABOLISM.

This study aimed to investigate whether prenatal alcohol exposure increases the risk of developing osteoarthritis in adult female offspring, particularly when combined with a high-fat diet after weaning. Researchers used a rat model where pregnant mothers were exposed to ethanol, and then examined the offspring's joint cartilage and cholesterol metabolism both as fetuses and as adults fed a high-fat diet.

The key findings revealed that female offspring with prenatal alcohol exposure developed osteoarthritis-like changes in their joint cartilage as adults, along with unhealthy cholesterol levels (higher bad cholesterol, lower good cholesterol). The researchers identified that this increased vulnerability was due to programming that occurred in the womb, which impaired the body's ability to clear cholesterol from cartilage tissue and reduced levels of a growth factor important for joint health.

These findings suggest that prenatal alcohol exposure creates a distinct phenotype of individuals who are particularly susceptible to joint degeneration when exposed to poor dietary conditions later in life. For physiotherapy and management, this research highlights the importance of identifying patients with prenatal alcohol exposure history, as they may benefit from early preventive interventions focusing on diet modification and joint protection strategies to reduce osteoarthritis risk.

DOES CHONDROCALCINOSIS ASSOCIATE WITH A DISTINCT RADIOGRAPHIC PHENOTYPE OF OSTEOARTHRITIS IN KNEES AND HIPS? A CASE-CONTROL STUDY.

This study investigated whether chondrocalcinosis (calcium crystal deposits in cartilage) creates distinct patterns of osteoarthritis damage in knee and hip joints. Researchers analyzed x-rays from 3,170 participants, comparing those with osteoarthritis plus chondrocalcinosis against those with osteoarthritis alone, measuring different types of joint damage including bone spurs, joint space narrowing, bone wearing away (attrition), cysts, and bone hardening.

The study found that chondrocalcinosis in the knee, or even at distant joints, was strongly linked to more severe bone surface wearing in knee osteoarthritis, while hip chondrocalcinosis was associated with milder overall hip osteoarthritis features. Importantly, chondrocalcinosis was not associated with excessive bone spur formation, contradicting previous assumptions about this osteoarthritis subtype.

These findings suggest that patients with chondrocalcinosis may represent distinct osteoarthritis subgroups requiring different management approaches, with knee cases potentially needing more aggressive joint preservation strategies due to increased bone surface damage, while hip cases might have a more favorable prognosis for conservative physiotherapy interventions.

INVESTIGATIONS OF POTENTIAL PHENOTYPES OF FOOT OSTEOARTHRITIS: CROSS-SECTIONAL ANALYSIS FROM THE CLINICAL ASSESSMENT STUDY OF THE FOOT.

This study aimed to identify distinct types of foot osteoarthritis (OA) by examining patterns of joint involvement and associated symptoms in 533 adults over age 50 with foot pain. Researchers used X-rays to assess OA in five key foot joints and applied statistical analysis to identify different patterns of disease. The analysis revealed three distinct groups: people with no or minimal foot OA (64%), those with OA affecting only the big toe joint (22%), and those with OA in multiple foot joints (15%). People with multi-joint foot OA had more severe symptoms, higher body weight, and were more likely to have arthritis in their finger joints, suggesting this represents a more systemic form of the disease that may require more comprehensive physiotherapy and management approaches.

EDITORIAL: UNRAVELING OSTEOARTHRITIS PATHOGENESIS: NEW INSIGHTS INTO PRERADIOGRAPHIC DISEASE AND PATIENT PHENOTYPES.

I apologize, but I cannot provide a meaningful summary of this research paper because the abstract is not available (marked as "NA").

To write an accurate summary focusing on the study objective, methods, findings about osteoarthritis phenotypes/subgroups, and implications for physiotherapy management, I would need access to the full abstract or key content from the paper.

If you could provide the abstract text or main content from this editorial about osteoarthritis pathogenesis and patient phenotypes, I would be happy to create the concise 3-4 sentence summary you requested in plain language.

DETERMINATION OF PAIN PHENOTYPES IN KNEE OSTEOARTHRITIS: A LATENT CLASS ANALYSIS USING DATA FROM THE OSTEOARTHRITIS INITIATIVE.

This study aimed to identify distinct pain-related subtypes within knee osteoarthritis by analyzing data from 3,494 participants using statistical modeling that groups people with similar characteristics. The researchers examined multiple factors including joint damage, muscle strength, psychological distress, pain sensitivity, and comorbidities to create these groupings.

The analysis revealed four distinct knee osteoarthritis phenotypes: a small comorbid group (4%) with multiple health conditions, a knee-sensitive group (24%) with high joint tenderness, a psychologically distressed group (10%) with depression and catastrophizing, and a mild phenotype (62%) with less severe symptoms overall. The psychologically distressed group experienced the worst pain and disability, while the mild phenotype had the least symptoms and best function.

These findings suggest that knee osteoarthritis patients should receive tailored treatments based on their specific phenotype - for example, addressing mental health in the distressed group, managing multiple conditions in the comorbid group, or using pain desensitization approaches for the knee-sensitive group rather than applying one-size-fits-all physiotherapy interventions.

MULTICOLOR FLOW CYTOMETRY-BASED CELLULAR PHENOTYPING IDENTIFIES OSTEOPROGENITORS AND INFLAMMATORY CELLS IN THE OSTEOARTHRITIC SUBCHONDRAL BONE MARROW COMPARTMENT.

This study aimed to develop a method for directly analyzing the types of cells present in the bone marrow beneath damaged cartilage in knee osteoarthritis patients. Researchers used flow cytometry (a cell analysis technique) to examine bone marrow cells extracted from knee bones of patients undergoing knee replacement surgery, identifying different cell populations without needing to grow them in culture first.

The analysis revealed distinct cell subgroups in osteoarthritic bone: approximately 20% of non-blood cells were bone-forming cells (osteoprogenitors), while over 80% of immune cells were inflammatory monocytes, along with specific populations of macrophages and bone-destroying cell precursors (osteoclast progenitors).

This cellular phenotyping approach could help physiotherapists and clinicians better understand why certain osteoarthritis patients respond differently to treatment, potentially leading to more personalized rehabilitation strategies that account for the underlying inflammatory and bone remodeling processes in individual patients.

DEVELOPMENT OF HAND PHENOTYPES AND CHANGES IN HAND PAIN AND PROBLEMS OVER TIME IN OLDER PEOPLE.

This study aimed to identify different patterns (phenotypes) of hand pain and function in older adults and track how these change over 6 years. Researchers analyzed questionnaire data from 5,617 adults aged 50+ at three time points, using statistical methods to identify distinct subgroups based on hand pain and function measures. They found five phenotypes ranging from "least affected" to "severely affected," with most people showing stability in their phenotype over time, though some with "high pain" improved to become "least affected." People with widespread body pain, hand nodes, sleep problems, and pain in both hands were more likely to develop severe hand problems, suggesting these factors could help physiotherapists identify patients who need more intensive early intervention and monitoring.

RESULTS OF OPERATIVE AND NONOPERATIVE TREATMENT OF ROCKWOOD TYPES III AND V ACROMIOCLAVICULAR JOINT DISLOCATION: A PROSPECTIVE, RANDOMIZED TRIAL WITH AN 18- TO 20-YEAR FOLLOW-UP.

This study aimed to compare long-term outcomes of surgical versus non-surgical treatment for severe acromioclavicular joint (shoulder) dislocations over 18-20 years. The researchers randomly assigned 25 patients with complete shoulder separations to either surgical repair (using wires and sutures) or conservative treatment (using a sling for 4 weeks), then assessed shoulder function, pain, and x-ray changes at long-term follow-up.

The study identified two distinct injury severity subgroups (Rockwood types III and V), with surgical treatment producing less joint prominence and instability, particularly in the less severe type III injuries, while both groups showed similar rates of arthritis development. Despite anatomical differences on x-rays, both treatment approaches resulted in equally good functional outcomes, with similar shoulder pain, strength, and daily activity scores after nearly two decades.

These findings suggest that physiotherapists can reassure patients that both surgical and conservative management lead to comparable long-term function, allowing treatment decisions to be individualized based on patient preferences, activity demands, and cosmetic concerns rather than fear of poor outcomes with either approach.

GENETIC POLYMORPHISM DIRECTS IL-6 EXPRESSION IN FIBROBLASTS BUT NOT SELECTED OTHER CELL TYPES.

This study investigated how genetic variations affect IL-6 production in different cell types from patients with rheumatoid arthritis and osteoarthritis. Researchers analyzed IL-6 expression in synovial fibroblasts and monocytes from joint tissues, examining the relationship with a specific genetic polymorphism (rs1800795) in the IL-6 gene promoter. The key finding was that fibroblasts from different patients consistently fell into three distinct groups (low, medium, and high IL-6 producers), with high producers being significantly associated with a specific genetic variant, while this same genetic pattern was not seen in monocytes. This suggests that osteoarthritis and rheumatoid arthritis patients may have different inflammatory phenotypes based on their genetics, which could help explain why anti-IL-6 treatments work better for some patients than others and may guide more personalized approaches to managing joint inflammation.

LITHIUM CHLORIDE DEPENDENT GLYCOGEN SYNTHASE KINASE 3 INACTIVATION LINKS OXIDATIVE DNA DAMAGE, HYPERTROPHY AND SENESCENCE IN HUMAN ARTICULAR CHONDROCYTES AND REPRODUCES CHONDROCYTE PHENOTYPE OF OBESE OSTEOARTHRITIS PATIENTS.

This study investigated how inactivation of the enzyme GSK3β affects cartilage cells (chondrocytes) in osteoarthritis, particularly comparing obese and non-obese patients. Researchers analyzed cartilage samples from patients and treated isolated chondrocytes with lithium chloride to block GSK3β activity, then measured various cellular changes including DNA damage, cell aging (senescence), and inflammatory markers. The key finding was that chondrocytes from obese osteoarthritis patients naturally showed higher levels of inactivated GSK3β and more cellular damage, while laboratory experiments confirmed that blocking GSK3β leads to increased oxidative stress, DNA damage, and premature cell aging that impairs normal cartilage cell function. These results suggest that obese osteoarthritis patients may represent a distinct disease subgroup with different underlying cellular mechanisms, which could require specialized treatment approaches rather than therapies aimed at blocking GSK3β activity.

SYNOVITIS AND RADIOGRAPHIC PROGRESSION IN NON-EROSIVE AND EROSIVE HAND OSTEOARTHRITIS: IS EROSIVE HAND OSTEOARTHRITIS A SEPARATE INFLAMMATORY PHENOTYPE?

This study aimed to determine whether erosive hand osteoarthritis represents a distinct inflammatory subtype by comparing inflammation levels, pain, and disease progression between erosive and non-erosive hand osteoarthritis patients. The researchers followed 65 participants over 5 years, using MRI, ultrasound, and clinical examinations to measure joint inflammation (synovitis) and X-rays to track structural changes.

The findings revealed that erosive hand osteoarthritis patients had significantly more severe inflammation, greater joint tenderness, and faster radiographic progression compared to those with non-erosive disease, even when accounting for existing structural damage. Importantly, the increased rate of joint deterioration in erosive cases occurred independently of baseline inflammation levels, suggesting these represent fundamentally different disease processes.

These results indicate that erosive hand osteoarthritis should be considered a separate, more aggressive inflammatory phenotype that may require different treatment approaches, potentially including more intensive anti-inflammatory interventions and closer monitoring in physiotherapy and rehabilitation programs.

DIFFERENCES IN DEMOGRAPHIC, CLINICAL, AND SYMPTOM CHARACTERISTICS AND QUALITY OF LIFE OUTCOMES AMONG ONCOLOGY PATIENTS WITH DIFFERENT TYPES OF PAIN.

This study aimed to identify different pain patterns in cancer patients receiving chemotherapy and examine how patient characteristics and quality of life differed between these groups. Researchers surveyed 926 cancer outpatients using questionnaires about their pain, symptoms, and quality of life, asking patients to specify whether their pain was cancer-related or not.

The study identified four distinct pain phenotypes: no pain (27.5%), only non-cancer pain (21.5% of total), only cancer pain (37.0% of total), and both types of pain (41.5% of total). Patients with both cancer and non-cancer pain were younger, more often female, had more health problems, and experienced significantly worse depression, anxiety, fatigue, and quality of life, while those with only non-cancer pain were older and commonly had osteoarthritis and back pain.

These findings suggest that pain assessment and management in cancer care should address both cancer-related and non-cancer conditions simultaneously, as patients experiencing both types face the greatest burden and may require more comprehensive, multidisciplinary approaches including physiotherapy for musculoskeletal conditions like osteoarthritis.

DELETION OF THE MEMBRANE COMPLEMENT INHIBITOR CD59A DRIVES AGE AND GENDER-DEPENDENT ALTERATIONS TO BONE PHENOTYPE IN MICE.

This study investigated how the deletion of CD59A, a protein that regulates complement system activity, affects bone structure in mice to better understand osteoarthritis development. Researchers used bone imaging and cellular analysis to examine bone changes in male and female mice lacking the CD59A gene compared to normal mice. The key finding was that male mice without CD59A developed a distinct bone phenotype characterized by longer, wider bones with reduced bone density and increased bone turnover, while female mice showed no such changes. These results suggest that complement system dysregulation may contribute to gender-specific osteoarthritis susceptibility, potentially informing future targeted therapies and highlighting the importance of considering sex differences when developing rehabilitation strategies for degenerative joint diseases.

PRELUDE TO A BIOLOGICAL PHENOTYPE FOR OSTEOARTHRITIS: COMMENTARY ON AN ARTICLE BY NOBUAKI CHINZEI, MD, PHD, ET AL.: "INFLAMMATION AND DEGENERATION IN CARTILAGE SAMPLES FROM PATIENTS WITH FEMOROACETABULAR IMPINGEMENT".

I apologize, but I cannot provide a meaningful summary based on the information provided. The title indicates this is a commentary piece about osteoarthritis biological phenotyping related to femoroacetabular impingement, but there is no abstract available ("NA") to analyze.

To write the requested 3-4 sentence summary focusing on study objectives, methods, findings about phenotypes/subgroups, and physiotherapy implications, I would need access to the actual abstract content or the full commentary text.

If you could provide the abstract or main content of this commentary, I would be happy to create a concise summary in plain language addressing the four key areas you've specified.

CHANGES IN ANTEROPOSTERIOR STABILITY AND PROPRIOCEPTION AFTER DIFFERENT TYPES OF KNEE ARTHROPLASTY.

This study aimed to compare how different types of knee replacement surgery affect knee stability and position sense in patients with good clinical outcomes (knee scores above 80 points). Researchers tested 40 patients (10 per group) who had received different implant types, measuring anteroposterior (front-to-back) knee movement using a specialized device and assessing joint position sense through proprioceptive tests.

The study identified distinct mechanical phenotypes among knee replacement types: unicompartmental knee arthroplasty (UKA) most closely replicated normal knee stability, while posterior-stabilized designs showed increased looseness at multiple knee angles, and medial pivot designs performed similarly to UKA except at the important 60-degree flexion angle. Despite these measurable differences in knee mechanics, all patients reported similarly good outcomes on standard questionnaires, and proprioception testing was inconclusive.

These findings suggest that while knee replacement surgery inevitably alters joint mechanics compared to the natural knee, patients can achieve excellent functional outcomes regardless of the specific implant design used. For physiotherapy practice, this indicates that rehabilitation protocols may need to account for different stability patterns depending on the implant type, particularly focusing on strengthening and movement control at specific knee angles where increased looseness occurs.

SULFORAPHANE REGULATES PHENOTYPIC AND FUNCTIONAL SWITCHING OF BOTH INDUCED AND SPONTANEOUSLY DIFFERENTIATING HUMAN MONOCYTES.

This study investigated whether sulforaphane (SFN), a natural compound found in broccoli and other cruciferous vegetables, could influence how immune cells called monocytes develop into different types of macrophages in osteoarthritis and rheumatoid arthritis. The researchers used laboratory cell cultures to test how SFN affected monocyte differentiation, measuring specific cell surface markers and inflammatory proteins to identify whether cells became pro-inflammatory (M1) or anti-inflammatory (M2) macrophages.

The key finding was that SFN treatment shifted monocytes away from developing into harmful M1 macrophages and instead promoted their development into beneficial M2 macrophages, particularly by blocking inflammatory responses triggered by collagen (a key inflammatory trigger in joint diseases). SFN also successfully converted existing M1 macrophages into M2 macrophages through specific cellular signaling pathways.

These results suggest that sulforaphane could potentially be used as a natural anti-inflammatory treatment for osteoarthritis and rheumatoid arthritis by modulating immune cell behavior, though this would need to be tested in human clinical trials before being incorporated into physiotherapy or treatment protocols.

RHEB: A POTENTIAL REGULATOR OF CHONDROCYTE PHENOTYPE FOR CARTILAGE TISSUE REGENERATION.

This study aimed to investigate how the RHEB gene controls chondrocyte (cartilage cell) behavior to improve cartilage regeneration treatments. The researchers used human chondrocytes in laboratory experiments, manipulating RHEB expression levels and testing the cells' ability to maintain their cartilage-producing characteristics during expansion and in tissue formation experiments. They found that RHEB helps chondrocytes maintain their natural cartilage-producing phenotype by preventing cell aging, maintaining proper cell identity, and reducing harmful oxidative stress - key factors that typically cause transplanted cartilage cells to lose their effectiveness. These findings could lead to improved cell-based therapies for osteoarthritis and cartilage injuries, potentially making chondrocyte transplantation more successful by ensuring the transplanted cells retain their ability to produce healthy cartilage tissue.

IN VIVO H1 MR SPECTROSCOPY USING 3 TESLA TO INVESTIGATE THE METABOLIC PROFILES OF JOINT FLUIDS IN DIFFERENT TYPES OF KNEE DISEASES.

This study aimed to investigate whether proton magnetic resonance spectroscopy (MRS) could identify different metabolic patterns in knee joint fluid across various knee conditions. The researchers used 3 Tesla MRI to analyze joint fluid in 84 patients with knee effusions, focusing on 38 patients with confirmed diagnoses: degenerative osteoarthritis (21 patients), traumatic injuries (12 patients), and infectious/inflammatory diseases (5 patients).

The study found three main lipid metabolites in knee joint fluid, but these could not statistically distinguish between the different disease types, suggesting that MRS alone cannot reliably identify specific knee condition phenotypes. However, subtle differences were observed - degenerative arthritis showed the highest ratio of certain lipid types, and infectious diseases showed a different metabolic pattern compared to degenerative and traumatic conditions.

While this technique shows promise for understanding the underlying biological mechanisms of different knee problems, it currently has limited practical application for diagnosing specific conditions or guiding physiotherapy treatment decisions, though it may contribute to future research on osteoarthritis subtypes.

NOCICEPTIVE PHENOTYPE ALTERATIONS OF DORSAL ROOT GANGLIA NEURONS INNERVATING THE SUBCHONDRAL BONE IN OSTEOARTHRITIC RAT KNEE JOINTS.

This study aimed to understand how nerve cells that sense pain in the subchondral bone (the bone layer beneath joint cartilage) change during osteoarthritis development in rat knee joints. Researchers used a chemical to induce arthritis in rats, then tracked specific nerve pathways using tracer injections and examined pain-related proteins (CGRP and TrkA) at early (2 weeks) and advanced (6 weeks) stages of the disease. The study found that pain-sensing nerve cells in the subchondral bone showed increased expression of pain markers and enlarged cell bodies, with these changes becoming more pronounced over time and strongly correlating with the severity of bone damage. These findings suggest that targeting the subchondral bone, particularly in advanced knee osteoarthritis, could be an important therapeutic approach, and that specific molecular targets (CGRP and TrkA) might be valuable for developing new pain treatments for patients with bone-related joint damage.

GUIDING SYNOVIAL INFLAMMATION BY MACROPHAGE PHENOTYPE MODULATION: AN IN VITRO STUDY TOWARDS A THERAPY FOR OSTEOARTHRITIS.

This study aimed to test whether four different compounds could reduce joint inflammation in osteoarthritis by changing the behavior of immune cells called macrophages. The researchers treated synovial tissue samples from OA patients with dexamethasone, rapamycin, BMP-7, or pravastatin, and tested how these compounds affected different types of macrophages in laboratory cultures. The key finding was that dexamethasone effectively reduced inflammation by suppressing harmful pro-inflammatory macrophages while promoting beneficial anti-inflammatory ones, whereas the other compounds had mixed or less favorable effects. The results suggest that targeting specific macrophage subtypes could lead to new OA treatments, but the effectiveness depends on the stage of disease, highlighting the importance of identifying different OA phenotypes to guide personalized therapy approaches.

MEASURING THE MUSCULOSKELETAL AGING PHENOTYPE.

This review aimed to examine how to measure the musculoskeletal aging phenotype in older adults, given the rapidly aging global population and the significant burden of musculoskeletal disease in those over 60. The authors identified four key interconnected components that make up the musculoskeletal aging phenotype: osteoporosis, osteoarthritis, sarcopenia, and frailty. They found that measurement tools and approaches vary considerably across these four areas, with osteoporosis measurement being more established while sarcopenia assessment methods are still rapidly evolving. Accurate measurement of these phenotypes is essential for identifying high-risk individuals, designing effective treatment trials, and developing targeted interventions that could slow or prevent the progression of age-related musculoskeletal decline.

TRANSIENT EXPRESSION OF THE DISEASED PHENOTYPE OF OSTEOARTHRITIC CHONDROCYTES IN ENGINEERED CARTILAGE.

This study aimed to determine whether chondrocytes (cartilage cells) from osteoarthritic joints retain their diseased characteristics when grown in laboratory culture. The researchers isolated chondrocytes from dogs with post-traumatic osteoarthritis and healthy controls, then grew them as small pellets while measuring inflammatory markers and cartilage-degrading enzymes over time. They found that osteoarthritic chondrocytes maintained their diseased phenotype for about two weeks in culture, producing different levels of inflammatory molecules (IL-8, KC-like protein) and matrix-degrading enzymes (MMPs) compared to healthy cells. These findings suggest that the "memory" of disease in cartilage cells is temporary, which could inform timing of treatments and help researchers better understand how osteoarthritis progresses and potentially responds to interventions.

SUBCHONDRAL BONE SCLEROSIS AND CANCELLOUS BONE LOSS FOLLOWING OA INDUCTION DEPEND ON THE UNDERLYING BONE PHENOTYPE.

This study aimed to investigate how underlying bone mass affects the progression of knee osteoarthritis (OA) in mice with different bone density characteristics. Researchers surgically induced OA in two mouse strains - one with naturally low bone mass and another with high bone mass - then compared cartilage damage and bone changes after 36 weeks using microscopic analysis and bone imaging.

The key finding was that while cartilage deterioration was similar regardless of initial bone density, the bone changes differed significantly between the two groups. Mice with higher baseline bone mass developed bone thickening (sclerosis) proportional to their starting bone thickness, while those with low bone mass experienced more widespread bone loss that extended beyond the immediate joint area.

These results suggest that people's underlying bone health may influence how their bones respond to OA, even if cartilage damage progresses similarly. This could have important implications for physiotherapy and treatment approaches, suggesting that bone health assessment and targeted interventions to maintain bone density might be particularly important for individuals with naturally lower bone mass who develop OA.

NOTOCHORDAL CELL CONDITIONED MEDIUM (NCCM) REGENERATES END-STAGE HUMAN OSTEOARTHRITIC ARTICULAR CHONDROCYTES AND PROMOTES A HEALTHY PHENOTYPE.

This study investigated whether notochordal cell conditioned medium (NCCM) from dogs could restore healthy function to damaged human cartilage cells from patients with severe osteoarthritis. Researchers cultured cartilage cells from both healthy donors and osteoarthritis patients requiring knee replacement surgery, then treated them with NCCM to measure changes in cartilage production and inflammation markers. The results showed that NCCM helped osteoarthritic cartilage cells produce significantly more healthy cartilage components while reducing harmful enzymes and inflammatory chemicals that break down cartilage. These findings suggest that NCCM could potentially be developed into a minimally invasive treatment for osteoarthritis, offering hope for slowing cartilage breakdown and promoting repair rather than relying solely on joint replacement surgery or anti-inflammatory medications.

A NOVEL TYPE II COLLAGEN GENE MUTATION IN A FAMILY WITH SPONDYLOEPIPHYSEAL DYSPLASIA AND EXTENSIVE INTRAFAMILIAL PHENOTYPIC DIVERSITY.

This study aimed to investigate a family with spondyloepiphyseal dysplasia (a bone and joint disorder) and identify the genetic cause behind their condition. The researchers examined seven affected family members across two generations using clinical assessments, X-rays, and genetic testing of the COL2A1 gene (which makes collagen for cartilage and bone).

They discovered a new genetic mutation that caused widely varying symptoms within the same family - from extremely short stature to normal height, and from severe hip deformities and arthritis to milder joint problems, though all members had spine abnormalities and hip issues. Some family members also had potentially serious neck instability.

For physiotherapy and management, this highlights the importance of individualized assessment and treatment plans, even when patients have the same genetic condition, as symptoms can vary dramatically between family members with identical mutations.

DECONSTRUCTING CHRONIC LOW BACK PAIN IN THE OLDER ADULT-STEP BY STEP EVIDENCE AND EXPERT-BASED RECOMMENDATIONS FOR EVALUATION AND TREATMENT. PART VIII: LATERAL HIP AND THIGH PAIN.

This study aimed to develop an evidence-based algorithm to help primary care providers diagnose and manage lateral hip and thigh pain in older adults, particularly as it relates to chronic low back pain. The researchers used a modified Delphi approach with expert panels including physiatrists, geriatricians, internists, and physical therapists to create diagnostic and treatment recommendations, supplemented by a clinical case example.

The main finding emphasizes that lateral hip and thigh pain often coexists with chronic low back pain in older adults, creating complex pain patterns where the true source of pain can be difficult to identify among multiple age-related degenerative changes. The algorithm provides a systematic step-by-step approach to distinguish between actual pain generators and incidental findings on imaging.

For physiotherapy and clinical management, this work supports taking a holistic, systematic approach when evaluating older adults with back pain, recognizing that hip and thigh pain may be contributing factors that require targeted treatment alongside back pain interventions.

EXPERIMENTAL PAIN PHENOTYPING IN COMMUNITY-DWELLING INDIVIDUALS WITH KNEE OSTEOARTHRITIS.

This study aimed to identify distinct pain sensitivity patterns in people with knee osteoarthritis using laboratory pain tests. Researchers tested 292 community-dwelling individuals with knee OA using multiple experimental pain methods (pressure, heat, cold, and punctate stimuli), then used statistical clustering to group participants based on their pain responses. The analysis revealed five distinct subgroups: low pain sensitivity (39 people), average sensitivity (88 people), high sensitivity specifically to repeated sharp pain (38 people), high cold pain sensitivity (80 people), and high heat pain sensitivity (41 people). These findings suggest that people with knee osteoarthritis have different underlying pain mechanisms, which could help physiotherapists and clinicians develop more personalized treatment approaches rather than using one-size-fits-all pain management strategies.

THE INCIDENT TIBIOFEMORAL OSTEOARTHRITIS WITH RAPID PROGRESSION PHENOTYPE: DEVELOPMENT AND VALIDATION OF A PROGNOSTIC PREDICTION RULE.

This study aimed to develop and validate a clinical prediction rule to identify people at high risk of developing rapidly progressing knee osteoarthritis within 4-5 years. The researchers analyzed data from over 4,000 participants across two large longitudinal studies, examining risk factors including obesity, age, knee alignment, symptoms, existing knee damage, and injury history using statistical modeling techniques. They identified four key predictors of rapid OA progression: having osteoarthritis in the opposite knee, mild existing knee damage (K&L grade 1), higher body mass index, and higher baseline disability scores, with the prediction model showing good accuracy (79-81%). This prediction tool could help physiotherapists and clinicians identify high-risk patients early for more intensive monitoring and preventive interventions, and assist researchers in selecting appropriate participants for clinical trials testing treatments to slow OA progression.

RELATIVE EFFICACY OF DIFFERENT TYPES OF EXERCISE FOR TREATMENT OF KNEE AND HIP OSTEOARTHRITIS: PROTOCOL FOR NETWORK META-ANALYSIS OF RANDOMISED CONTROLLED TRIALS.

This study aims to compare the effectiveness of different types of exercise for treating knee and hip osteoarthritis, since direct head-to-head comparisons between exercise types are rare. The researchers will conduct a network meta-analysis using data from randomized controlled trials, analyzing pain as the primary outcome and function/quality of life as secondary outcomes. The study will include subgroup analyses based on patient, study, and disease characteristics to identify how different factors might influence treatment responses. This research will provide the first comprehensive evidence ranking different exercise approaches against each other, which could help physiotherapists and clinicians choose the most effective exercise programs for individual patients with osteoarthritis.

DO DIFFERENT TYPES OF BEARINGS AND NOISE FROM TOTAL HIP ARTHROPLASTY INFLUENCE HIP-RELATED PAIN, FUNCTION, AND QUALITY OF LIFE POSTOPERATIVELY?

This study aimed to compare patient-reported outcomes between different types of hip replacement bearings (ceramic-on-ceramic, metal-on-metal, and metal-on-polyethylene) and examine how joint noise affects patient satisfaction and function. The researchers conducted a nationwide survey of 3,089 hip replacement patients from the Danish registry, using validated questionnaires measuring pain, function, quality of life, and activity levels.

The study identified distinct patient subgroups based on bearing type and noise occurrence: ceramic-on-ceramic and metal-on-metal patients reported noise twice as frequently as metal-on-polyethylene patients (27-29% vs 12%), and patients with noisy hips consistently reported worse outcomes across all measures except activity levels. While bearing materials showed similar overall outcomes, ceramic-on-ceramic patients experienced more hip-related symptoms.

These findings suggest that physiotherapists and clinicians should specifically assess for joint noise complaints during post-surgical evaluations, as this may indicate a subgroup of patients requiring additional support or modified rehabilitation approaches to address the functional and psychological impacts of audible joint sounds.

THE C-TERMINAL DOMAIN OF CONNEXIN43 MODULATES CARTILAGE STRUCTURE VIA CHONDROCYTE PHENOTYPIC CHANGES.

This study investigated how a specific part of the connexin43 protein (the C-terminal domain) affects cartilage health and chondrocyte cell behavior. Researchers used genetically modified mice lacking this protein domain and examined their cartilage structure, cell communication, and key cellular characteristics. They found that mice without this domain had smaller body size, reduced cell-to-cell communication, increased cell proliferation, and decreased production of important cartilage components like collagen type II and proteoglycans - indicating abnormal chondrocyte phenotypes. These findings suggest that damage to connexin43 during inflammation or injury (common in osteoarthritis) may contribute to cartilage breakdown, potentially identifying new targets for treatments aimed at preserving healthy chondrocyte function and cartilage structure.

SYNOVIAL FLUID FROM PATIENTS WITH RHEUMATOID ARTHRITIS MODULATES MONOCYTE CELL-SURFACE PHENOTYPE.

This study investigated how synovial fluid from rheumatoid arthritis (RA) and osteoarthritis (OA) patients affects immune cell behavior, specifically examining whether different joint diseases create distinct inflammatory environments. Researchers exposed healthy immune cells (monocytes) to synovial fluid from RA or OA patients and measured changes in cell surface markers and inflammatory responses using flow cytometry and cell culture techniques. The key finding was that RA synovial fluid created a more pro-inflammatory phenotype compared to OA fluid, with monocytes showing increased activation markers (higher CD86, lower ILT4) that correlated with disease severity, and subsequently triggering stronger inflammatory responses in T-cells. These results suggest that RA and OA represent distinct inflammatory phenotypes at the cellular level, which could inform the development of more targeted anti-inflammatory treatments and help physiotherapists understand why patients with these different conditions may respond differently to rehabilitation approaches.

IDENTIFICATION OF CLINICAL PHENOTYPES IN KNEE OSTEOARTHRITIS: A SYSTEMATIC REVIEW OF THE LITERATURE.

This systematic review aimed to identify distinct clinical phenotypes (subgroups) of knee osteoarthritis patients by examining patterns of patient characteristics and disease features across existing research. The researchers searched PubMed for studies that used statistical methods to group knee osteoarthritis patients, then analyzed 24 high-quality studies to identify common patterns. They found strong evidence for six distinct phenotypes: chronic pain with central sensitization, inflammatory (high inflammation markers), metabolic syndrome (linked to obesity and diabetes), altered bone/cartilage metabolism, mechanical overload (often with knee malalignment), and minimal joint disease (mild symptoms with slow progression). These findings suggest that knee osteoarthritis patients should be assessed and treated differently based on their phenotype - for example, patients with chronic pain phenotypes may benefit more from pain management strategies, while those with mechanical problems might need movement-focused physiotherapy interventions.

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This study aimed to understand how mutations in the DMP1 gene (associated with hypophosphatemic rickets) lead to severe osteoarthritis by examining DMP1 knockout mice over their lifespan. The researchers used multiple imaging and histological techniques to characterize joint changes, created conditional knockout mice to test direct effects on cartilage, and tested whether dietary phosphate supplementation could improve outcomes.

The mice developed a unique osteoarthritis phenotype with a distinctive two-phase pattern: initial expansion of cartilage cells at 1 month followed by rapid cartilage loss by 3 months, plus typical OA features like cartilage degradation and bone spurs. Importantly, when DMP1 was removed only from cartilage cells (rather than the whole body), no joint problems occurred, and high-phosphate diet treatment for 8 weeks significantly improved the OA-like changes.

These findings suggest that DMP1-related osteoarthritis represents a distinct subgroup caused by phosphate imbalance rather than direct cartilage defects. For physiotherapy management, this implies that patients with hypophosphatemic rickets may require specialized approaches addressing their unique biphasic cartilage changes, and that systemic phosphate correction (rather than just local joint treatments) may be crucial for preventing or managing their osteoarthritis.

PRO-INFLAMMATORY CYTOKINES AND STRUCTURAL BIOMARKERS ARE EFFECTIVE TO CATEGORIZE OSTEOARTHRITIS PHENOTYPE AND PROGRESSION IN STANDARDBRED RACEHORSES OVER FIVE YEARS OF RACING CAREER.

This study aimed to track biomarker changes in racehorses with post-traumatic osteoarthritis (PTOA) over 5 years to understand disease progression and identify different patterns of joint degeneration. Researchers measured inflammatory markers (IL1-β, IL-6, TNF-α) and structural damage markers (CTXII, COMP) in blood and joint fluid annually in horses who developed fetlock joint injuries during their first racing year, compared to healthy controls.

The study identified distinct phases of PTOA progression: inflammatory markers peaked immediately after injury, decreased at year 1, then progressively increased from year 3 onward, while structural damage markers remained normal initially but rose significantly from years 2-3. TNF-α levels in joint fluid were particularly useful for predicting which horses would show worsening joint damage on X-rays.

These findings suggest there may be a critical early window (around year 1 when inflammation naturally decreases) where targeted interventions could potentially slow disease progression, and that TNF-α monitoring could help physiotherapists and clinicians identify patients at highest risk of joint deterioration requiring more intensive management.

EFFECTS OF MECHANICAL STRESS ON CHONDROCYTE PHENOTYPE AND CHONDROCYTE EXTRACELLULAR MATRIX EXPRESSION.

This study aimed to understand how mechanical stress affects cartilage cells (chondrocytes) and their surrounding matrix in osteoarthritis development. Researchers examined cartilage from different joint regions using microscopy and mechanical testing, and applied controlled stretching forces to human cartilage cells in the laboratory while measuring their properties and gene expression. The findings showed that cartilage in different joint areas had distinct characteristics and mechanical properties, and that mechanical stress changed how chondrocytes behaved and produced their surrounding matrix proteins. These results suggest that understanding how different joint regions respond to mechanical loading could help develop more targeted physiotherapy approaches that consider the specific mechanical environment and cellular responses in different areas of arthritic joints.

NOVEL ROLE OF CCN3 THAT MAINTAINS THE DIFFERENTIATED PHENOTYPE OF ARTICULAR CARTILAGE.

This study investigated the role of CCN3 protein in maintaining healthy cartilage and its potential as a treatment for osteoarthritis. Researchers used a chemical model to induce osteoarthritis in rats, then tested CCN3 effects both in laboratory cell cultures and in living animals during early disease stages. They found that CCN3 levels dropped when osteoarthritis developed, but when CCN3 was added back, it helped cartilage cells produce important protective substances like lubricin (which helps joints move smoothly) and maintained cartilage structure. These findings suggest that CCN3 could potentially be developed as a disease-modifying treatment for osteoarthritis, offering physiotherapists and clinicians a future therapeutic option that might help preserve joint cartilage rather than just managing symptoms.

SYSTEMATIC REVIEW OF RHEUMATIC DISEASE PHENOTYPES AND OUTCOMES IN THE INDIGENOUS POPULATIONS OF CANADA, THE USA, AUSTRALIA AND NEW ZEALAND.

This systematic review aimed to characterize how rheumatic diseases present and progress in Indigenous populations across Canada, USA, Australia, and New Zealand to better understand their healthcare needs. The researchers searched medical and Indigenous databases through 2015, reviewing over 5,000 studies and ultimately including 85 studies that reported on disease features and outcomes in these populations.

The review identified distinct disease phenotypes in Indigenous populations, including more severe rheumatoid arthritis with higher disease activity and worse quality of life, more frequent kidney involvement in lupus, advanced spondyloarthropathy presentations, and more severe gout and osteoarthritis in New Zealand Māori populations compared to non-Indigenous groups. However, most studies focused on North American populations, with limited research from Australia and New Zealand.

These findings suggest Indigenous patients may require more intensive management approaches and culturally appropriate physiotherapy interventions, though the authors emphasize the need for future research to distinguish whether these differences reflect true biological variations or disparities in healthcare access and treatment timing.

DYNAMIC CYCLIC COMPRESSION MODULATES THE CHONDROGENIC PHENOTYPE IN HUMAN CHONDROCYTES FROM LATE STAGE OSTEOARTHRITIS.

This study investigated whether mechanical compression loading could improve the damaged cellular characteristics of cartilage cells from patients with severe osteoarthritis. The researchers applied rhythmic compression forces to these cells grown in laboratory conditions and measured changes in key cellular markers related to cartilage health and breakdown. They found that mechanical loading helped restore normal cartilage cell function by increasing beneficial factors (like SOX9) and reducing harmful enzymes that break down cartilage matrix. These findings suggest that controlled mechanical loading through physiotherapy or exercise programs could potentially help repair cartilage damage in advanced osteoarthritis by reactivating the cells' natural repair mechanisms.

INCIDENT MYOCARDIAL INFARCTION ASSOCIATED WITH MAJOR TYPES OF ARTHRITIS IN THE GENERAL POPULATION: A SYSTEMATIC REVIEW AND META-ANALYSIS.

This systematic review and meta-analysis aimed to compare heart attack risks across five major types of arthritis (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout, and osteoarthritis) using population-based studies. The researchers analyzed 25 studies through meta-analysis to calculate pooled risk estimates for each arthritis type.

The study found that people with all types of arthritis had increased heart attack risk, with rheumatoid arthritis showing the highest risk (69% increase), followed by gout (47% increase), psoriatic arthritis (41% increase), and osteoarthritis (31% increase). This increased risk was partly explained by higher rates of traditional cardiovascular risk factors like high blood pressure and diabetes in people with arthritis.

These findings suggest that physiotherapists and healthcare providers should take a more comprehensive approach when treating people with arthritis, addressing both joint inflammation and cardiovascular health through integrated exercise programs and lifestyle interventions that target traditional heart disease risk factors.

ROCK/ACTIN/MRTF SIGNALING PROMOTES THE FIBROGENIC PHENOTYPE OF FIBROBLAST-LIKE SYNOVIOCYTES DERIVED FROM THE TEMPOROMANDIBULAR JOINT.

This study aimed to understand the cellular mechanisms behind fibrosis (scarring) in temporomandibular joint (TMJ) osteoarthritis, which contributes to jaw stiffness. Researchers used mouse TMJ cells and tested various chemical inhibitors to examine how the ROCK/ACTIN/MRTF signaling pathway controls the transformation of normal joint cells into scar-forming myofibroblasts. They found that this specific signaling pathway strongly promotes the development of fibrotic cell characteristics, and that blocking different parts of this pathway successfully reduced scar tissue formation markers. These findings suggest that TMJ osteoarthritis involves a distinct fibrotic phenotype driven by mechanical stress, and targeting this pathway could lead to new treatments that may complement physiotherapy approaches for managing jaw stiffness and improving joint function.

PHYTOESTROGEN (DAIDZEIN) PROMOTES CHONDROGENIC PHENOTYPE OF HUMAN CHONDROCYTES IN 2D AND 3D CULTURE SYSTEMS.

This study investigated whether daidzein, a plant-based estrogen (phytoestrogen), could help maintain healthy cartilage cell characteristics as a potential osteoarthritis treatment without the side effects of hormone therapy. Researchers tested daidzein on human cartilage cells grown in laboratory dishes (2D) and on special scaffolds (3D), measuring the production of cartilage-building materials like collagen and glycosaminoglycans, as well as gene activity. The results showed that low doses of daidzein significantly increased production of these important cartilage components and activated genes responsible for maintaining healthy cartilage cells, with particularly strong effects in the 3D environment. These findings suggest that daidzein could potentially be developed as a natural therapeutic option for osteoarthritis management, especially for postmenopausal women, though clinical trials would be needed to confirm its effectiveness in actual patients.

KNEE AND HIP INTRA-ARTICULAR ADIPOSE TISSUES (IAATS) COMPARED WITH AUTOLOGOUS SUBCUTANEOUS ADIPOSE TISSUE: A SPECIFIC PHENOTYPE FOR A CENTRAL PLAYER IN OSTEOARTHRITIS.

This study aimed to compare the characteristics of fat tissues inside joints (infrapatellar, suprapatellar, and hip fat pads) with fat tissue under the skin in osteoarthritis patients. Researchers collected these tissues during knee and hip replacement surgeries from 43 patients and analyzed their structure, inflammation levels, and gene expression patterns. The key finding was that all joint fat tissues showed a distinct inflammatory phenotype compared to subcutaneous fat, with increased fibrosis, blood vessel formation, immune cell infiltration, and higher levels of inflammatory molecules like IL-6 and IL-8. These results suggest that joint fat tissues may contribute significantly to osteoarthritis progression through inflammation, indicating that targeting these tissues could be important for developing new treatments, though this research doesn't directly impact current physiotherapy approaches.

ERRATUM TO: CAN WE IDENTIFY PATIENTS WITH HIGH RISK OF OSTEOARTHRITIS PROGRESSION WHO WILL RESPOND TO TREATMENT? A FOCUS ON EPIDEMIOLOGY AND PHENOTYPE OF OSTEOARTHRITIS.

I cannot provide a meaningful summary of this research as this appears to be an erratum (correction) notice with no abstract content available.

To write an effective summary focusing on osteoarthritis phenotyping, patient risk stratification, treatment response prediction, and physiotherapy implications, I would need access to either:
- The original research paper's abstract and methods
- The corrected abstract content
- Details about what specific corrections were made in this erratum

If you could provide the original paper's abstract or the corrected content, I'd be happy to summarize the study's objectives, methodology, phenotyping findings, and clinical management implications.

PRESENCE OF IL-17 IN SYNOVIAL FLUID IDENTIFIES A POTENTIAL INFLAMMATORY OSTEOARTHRITIC PHENOTYPE.

This study aimed to investigate whether IL-17, an inflammatory protein, could help identify a specific subtype of osteoarthritis patients with distinct characteristics. The researchers analyzed synovial fluid (joint fluid) and blood samples from 152 patients undergoing hip or knee replacement surgery, measuring various inflammatory markers and comparing them with clinical symptoms and X-ray findings.

The study identified that 9% of patients had detectable IL-17 in their joint fluid, and these patients showed a unique "inflammatory phenotype" characterized by higher levels of other inflammatory markers (IL-6, leptin, resistin) and pain-related substances, but paradoxically had less severe structural joint damage on X-rays compared to patients without IL-17. Interestingly, despite the increased inflammation, these patients did not report worse pain or function.

These findings suggest there may be a distinct inflammatory subgroup of osteoarthritis patients who could potentially benefit from targeted anti-inflammatory treatments, which could inform more personalized physiotherapy and medical management approaches rather than using a one-size-fits-all treatment strategy.

ASSOCIATIONS BETWEEN OBESITY AND THE RADIOGRAPHIC PHENOTYPE IN KNEE OSTEOARTHRITIS.

This study investigated how obesity relates to different X-ray patterns in knee osteoarthritis among 734 women. Researchers classified participants into groups based on whether their knee X-rays showed mainly bone spurs (osteophytes), joint space narrowing, both features equally, or normal appearance. The key finding was that obese women were much more likely to have the osteophyte-dominant pattern compared to non-obese women (74.5% vs 38%), with obesity being strongly linked to bone spur formation but only weakly associated with joint space narrowing. These results suggest that obese patients with knee osteoarthritis may represent a distinct subgroup with predominantly bone spur formation, which could influence treatment decisions and help physiotherapists tailor interventions based on the underlying disease pattern.

ANALYSIS OF THERAPEUTIC EFFECTIVENESS OF SELECTED TYPES OF COLLAGEN IN PREVENTION AND TREATMENT OF DEGENERATIVE JOINT DISEASE.

This study aimed to review and analyze the therapeutic effectiveness of different collagen types for preventing and treating osteoarthritis (OA). The researchers conducted a literature review using evidence-based medicine principles, examining studies ranging from laboratory (in vitro) experiments to human clinical trials (in vivo), including animal studies, tissue engineering approaches, and collagen scaffold development. The findings suggest that newer injectable medical collagen preparations show promising therapeutic benefits, demonstrating both pain-relieving properties and the ability to promote tissue regeneration at the cellular level. These results indicate that collagen-based treatments could become valuable components of comprehensive OA management, potentially offering physiotherapists and clinicians additional options for improving patient function and supporting joint tissue repair alongside traditional rehabilitation approaches.

QUANTITATIVE GENETICS OF CIRCULATING HYALURONIC ACID (HA) AND ITS CORRELATION WITH HAND OSTEOARTHRITIS AND OBESITY-RELATED PHENOTYPES IN A COMMUNITY-BASED SAMPLE.

This study aimed to investigate how genetics and obesity-related factors influence blood levels of hyaluronic acid (HA), a potential biomarker for osteoarthritis. The researchers analyzed data from 911 healthy European individuals, measuring HA levels, hand arthritis on X-rays, body composition, and metabolic factors, then used genetic modeling to determine how much genetics versus environment contributed to these traits.

The study found that HA levels were linked to age, hand arthritis severity, body fat measures, and waist-to-hip ratio, with genetics accounting for a substantial 66% of the variation in HA levels between individuals. Different traits showed varying degrees of genetic influence, ranging from 12% for waist-to-hip ratio to 46% for joint space narrowing in hand arthritis.

These findings suggest that HA levels as a biomarker for osteoarthritis are heavily influenced by a person's genetic makeup and metabolic health, indicating that osteoarthritis may have distinct subgroups based on these underlying factors. For physiotherapy practice, this implies that treatment approaches may need to be tailored based on individual metabolic profiles and genetic predisposition, with particular attention to managing obesity-related factors in osteoarthritis care.

NON-STEROIDAL ANTI-INFLAMMATORY DRUG RELATED UPPER GASTROINTESTINAL BLEEDING: TYPES OF DRUG USE AND PATIENT PROFILES IN REAL CLINICAL PRACTICE.

This study aimed to understand the real-world characteristics and patterns of NSAID use among patients hospitalized for upper gastrointestinal bleeding, since most previous research focused only on patients with chronic rheumatic diseases. The researchers conducted a large case-control study comparing 3,785 patients with endoscopy-proven upper GI bleeding to 6,540 controls, using logistic regression to analyze bleeding risks and patient profiles.

The study identified distinct patient subgroups: those using NSAIDs for acute musculoskeletal pain (36.1% - the largest group), chronic osteoarthritis (13.5%), and headaches (13.6%), with significant demographic differences between acute and chronic pain users. Importantly, the majority of patients (around 65%) had been using NSAIDs short-term rather than long-term, and only about 17% of bleeding cases were taking NSAIDs specifically for chronic osteoarthritis.

These findings suggest that current prevention strategies for NSAID-related complications may be inadequate since they primarily target patients with chronic rheumatic conditions, while most bleeding events occur in short-term users with acute musculoskeletal problems who may not receive appropriate risk counseling or protective medications from healthcare providers.

ASSOCIATIONS BETWEEN PROXIMAL TIBIOFIBULAR JOINT (PTFJ) TYPES AND KNEE OSTEOARTHRITIC CHANGES IN OLDER ADULTS.

This study aimed to examine how different anatomical shapes of the proximal tibiofibular joint (PTFJ) - the small joint where the top of the fibula meets the tibia - relate to knee osteoarthritis changes in older adults. Researchers used MRI scans to classify PTFJ shapes in 967 community participants and measured various signs of knee osteoarthritis including cartilage loss, defects, bone swelling, and bone spurs.

The study identified seven distinct PTFJ shape types, with the most common being plane (49%) and trochoid (32%) configurations, while five "irregular" types were less frequent but showed important associations with knee problems. Participants with irregular PTFJ shapes had significantly more osteoarthritis changes - including less cartilage, more cartilage damage, bone marrow lesions, and bone spurs - specifically in the outer (lateral) compartment of the knee, while the inner (medial) compartment was unaffected.

These findings suggest that PTFJ anatomy may represent an important structural phenotype that predisposes certain individuals to lateral compartment knee osteoarthritis. For physiotherapy practice, this could indicate that patients with lateral-dominant knee osteoarthritis symptoms might benefit from targeted interventions addressing lateral compartment loading patterns and fibular mobility, though more research is needed to establish whether PTFJ

PAIN AND MORTALITY IN OLDER ADULTS: THE INFLUENCE OF PAIN PHENOTYPE.

This study aimed to determine whether different pain phenotypes influence mortality risk in older adults aged 50 and above. The researchers analyzed data from two large population cohorts (totaling 17,309 participants) using survival analysis to compare mortality rates across different pain characteristics, including pain extent (number of sites, widespread pain) and pain impact (interference with daily activities, being troubled by pain).

The key finding was that pain phenotypes characterized by functional impact were associated with higher mortality risk, while pain extent was not - specifically, people "often troubled with pain" had a 29% increased mortality risk, and those with moderate to extreme pain interference had 38-88% increased risk. In contrast, simply having pain or widespread pain did not significantly increase mortality risk.

These findings suggest that physiotherapy and pain management should prioritize reducing pain's interference with daily activities rather than just focusing on pain intensity or number of pain sites, as functional impact appears more clinically meaningful for long-term health outcomes.

IS THE ATROPHIC PHENOTYPE OF TIBIOFEMORAL OSTEOARTHRITIS ASSOCIATED WITH FASTER PROGRESSION OF DISEASE? THE MOST STUDY.

This study aimed to determine whether people with the "atrophic" type of knee osteoarthritis (characterized by joint space narrowing but minimal bone spurs) experience faster disease progression than those with non-atrophic osteoarthritis. Researchers followed 476 knees from 432 participants for 30 months, using X-rays and MRI scans to identify atrophic cases (10.5% by X-ray, 3.4% by MRI) and track cartilage loss and joint space narrowing over time. Contrary to expectations, the study found that knees with atrophic osteoarthritis actually progressed more slowly than those with non-atrophic osteoarthritis, with less likelihood of rapid cartilage damage and joint space narrowing. These findings suggest that the atrophic phenotype may represent a less aggressive form of knee osteoarthritis, which could inform treatment planning and help physiotherapists better tailor rehabilitation strategies based on individual disease patterns.

DECONSTRUCTING A POPULAR MYTH: WHY KNEE ARTHROSCOPY IS NO BETTER THAN PLACEBO SURGERY FOR DEGENERATIVE MENISCAL TEARS.

I apologize, but I cannot provide a meaningful summary of this study as the abstract is listed as "NA" (not available).

To write an accurate summary focusing on the study objective, methods, findings about osteoarthritis phenotypes/subgroups, and implications for physiotherapy management, I would need access to the actual abstract content.

If you could provide the complete abstract, I would be happy to create a concise 3-4 sentence summary in plain language that addresses the key points you've requested regarding knee arthroscopy effectiveness and its relevance to osteoarthritis management.

RESISTIN PROMOTES THE ABNORMAL TYPE I COLLAGEN PHENOTYPE OF SUBCHONDRAL BONE IN OBESE PATIENTS WITH END STAGE HIP OSTEOARTHRITIS.

This study investigated how body weight affects bone structure and composition in patients with severe hip osteoarthritis requiring surgery. Researchers compared bone samples from the hip joint of normal-weight versus overweight/obese patients using advanced imaging and laboratory techniques to analyze bone architecture and collagen properties. The key finding was that overweight/obese patients had weaker, thinner bone structure and abnormal collagen composition, driven by higher levels of a hormone called resistin that is produced by fat tissue. These results suggest that obesity creates a distinct osteoarthritis subtype with compromised bone quality, indicating that weight management should be a critical component of treatment plans and that physiotherapy interventions may need to be modified to account for the weaker bone structure in obese patients with hip osteoarthritis.

BENEFICIAL EFFECT OF RESVERATROL ON PHENOTYPIC FEATURES AND ACTIVITY OF OSTEOARTHRITIC OSTEOBLASTS.

This study investigated whether resveratrol (a natural compound) could improve the abnormal behavior of bone-forming cells (osteoblasts) in osteoarthritis patients. Researchers compared osteoblasts from knee bones of OA patients versus healthy individuals, then tested how resveratrol treatment affected various cellular functions and signaling pathways. The key finding was that OA osteoblasts have distinct abnormal characteristics - they produce excessive enzymes and proteins but create poorly mineralized bone - and resveratrol partially corrected some of these problems by improving bone mineralization and restoring beneficial cellular pathways. While this laboratory research doesn't directly translate to physiotherapy practice yet, it suggests that targeting the bone component of OA (not just cartilage) could be important, and natural compounds like resveratrol might eventually complement rehabilitation approaches for managing this complex joint disease.

RAPAMYCIN MAINTAINS THE CHONDROCYTIC PHENOTYPE AND INTERFERES WITH INFLAMMATORY CYTOKINE INDUCED PROCESSES.

This laboratory study investigated whether rapamycin (an mTORC1 inhibitor) could protect cartilage cells from inflammatory damage in osteoarthritis. The researchers exposed patient-derived chondrocytes (cartilage cells) to inflammatory molecules (TNF-α and IL-1β) with and without rapamycin treatment, then measured cartilage breakdown, cell death, and inflammatory markers using various laboratory assays. The key findings showed that rapamycin successfully reduced cartilage matrix degradation, prevented cell death, maintained healthy cartilage cell characteristics, and decreased inflammatory processes even in the presence of damaging inflammatory signals. These results suggest rapamycin could be a promising addition to current osteoarthritis treatments, potentially offering a new therapeutic approach that targets the inflammatory processes underlying cartilage destruction, though clinical trials would be needed to confirm its effectiveness in patients.

BIOMARKERS REFLECT DIFFERENCES IN OSTEOARTHRITIS PHENOTYPES OF THE LUMBAR SPINE: THE JOHNSTON COUNTY OSTEOARTHRITIS PROJECT.

This study aimed to identify whether blood biomarkers could distinguish between different types of lumbar spine osteoarthritis affecting either the facet joints, the intervertebral discs, or both structures. Researchers analyzed data from 555 participants, measuring levels of hyaluronan (HA, an inflammation marker) and CTX-II (a marker of cartilage breakdown) in blood samples, while categorizing spine degeneration patterns using X-rays.

The study found three distinct phenotypes with different biomarker signatures: facet joint osteoarthritis alone (22% of participants) was associated with higher HA levels, while spine osteoarthritis affecting discs (15% of participants) was linked to elevated CTX-II levels. The combination of both conditions (35% of participants) did not show clear biomarker associations.

These findings suggest that different parts of the spine undergo distinct degenerative processes - facet joints showing more inflammation while disc degeneration involves more cartilage breakdown. This research could help physiotherapists and clinicians develop more targeted treatment approaches, with anti-inflammatory strategies potentially benefiting facet joint problems and cartilage-protective interventions being more relevant for disc-related spine osteoarthritis.

EXPOSURE TO REVERSINE AFFECTS THE CHONDROCYTE MORPHOLOGY AND PHENOTYPE IN VITRO.

This study investigated whether reversine (REV), a chemical compound, could restore the regenerative potential of chondrocytes (cartilage cells) taken from osteoarthritic joints, which typically have poor capacity for cartilage repair. Researchers treated osteoarthritic chondrocytes with REV for 6 days and analyzed changes in cell shape, gene expression, and cartilage-forming ability using various laboratory techniques.

REV treatment caused the cells to adopt a more rounded, chondrocyte-like shape and increased expression of some cartilage markers (SOX9, aggrecan) and growth factors, while reducing inflammatory markers and cell proliferation. However, the cells failed to produce adequate levels of type II collagen, a crucial component of healthy cartilage, indicating incomplete restoration of normal chondrocyte function.

While REV showed promise in partially reversing some degenerative changes in osteoarthritic chondrocytes, it did not fully restore their cartilage-forming potential, suggesting limitations for tissue engineering applications in cartilage repair and osteoarthritis treatment.

CARTILAGE-SPECIFIC DELETION OF ALK5 GENE RESULTS IN A PROGRESSIVE OSTEOARTHRITIS-LIKE PHENOTYPE IN MICE.

This study investigated how a specific cellular signaling pathway (TGF-β/ALK5) affects cartilage health and osteoarthritis development using genetically modified mice. Researchers created mice that lacked the ALK5 gene specifically in cartilage cells and used various laboratory techniques to examine cartilage structure, gene expression, and cell death over time. The mice without ALK5 developed a progressive osteoarthritis-like condition characterized by cartilage breakdown, joint inflammation, bone spurs, and increased cartilage cell death - essentially mimicking human osteoarthritis patterns. These findings suggest that the TGF-β/ALK5 pathway is crucial for maintaining healthy cartilage by regulating protective factors, indicating that treatments targeting this pathway or its downstream effects (particularly PRG4 protein production) could potentially slow osteoarthritis progression and inform rehabilitation strategies focused on preserving cartilage function.

NON-SYNONYMOUS WNT16 POLYMORPHISMS ALLELES ARE ASSOCIATED WITH DIFFERENT OSTEOARTHRITIS PHENOTYPES.

This study investigated whether genetic variations in the WNT16 gene are associated with different types of osteoarthritis (OA) in 509 patients requiring joint replacement surgery. Researchers analyzed two specific genetic variants and classified patients' OA as either "atrophic" (bone-thinning) or "hypertrophic" (bone-thickening) types using X-rays.

The key finding was that certain genetic variants were significantly more common in men with the hypertrophic (bone-growing) form of OA in both hip and knee joints, suggesting that genetics may influence which type of OA a person develops. This research indicates that OA should not be viewed as a single condition but rather as distinct subtypes with different underlying genetic factors, which could lead to more personalized treatment approaches in physiotherapy and medical management based on a patient's specific OA type and genetic profile.

MICRORNA-143 AND -145 MODULATE THE PHENOTYPE OF SYNOVIAL FIBROBLASTS IN RHEUMATOID ARTHRITIS.

This study aimed to identify specific microRNAs that distinguish rheumatoid arthritis (RA) from osteoarthritis by examining how they affect synovial tissue cells. The researchers used microarray analysis to compare microRNA and gene expression patterns in synovial fibroblasts from RA patients versus osteoarthritis patients, then performed laboratory experiments to understand the functional relationships.

The key findings revealed that two specific microRNAs (miR-143 and miR-145) were significantly elevated in RA synovial fibroblasts compared to osteoarthritis cells. These microRNAs suppress protective genes (IGFBP5 and SEMA3A), making the synovial cells more responsive to inflammatory signals and promoting harmful processes like inflammation, cell survival, and tissue invasion that characterize RA.

These findings suggest that RA and osteoarthritis represent distinct disease phenotypes at the molecular level, which could lead to more targeted treatments. For physiotherapy and rehabilitation, this research indicates that RA patients may require different management approaches than osteoarthritis patients, and targeting these specific microRNAs could potentially complement physical therapy interventions to better control joint inflammation and tissue damage.

SPONTANEOUS HYPERTENSIVE RAT EXHIBITS BONE AND MENISCUS PHENOTYPES OF OSTEOARTHRITIS: IS IT AN APPROPRIATE CONTROL FOR METS-ASSOCIATED OA?

I apologize, but I cannot provide a meaningful summary of this research as the abstract is listed as "NA" (not available).

To write an effective summary focusing on the study objective, methods, findings about osteoarthritis phenotypes, and implications for physiotherapy management, I would need access to the actual abstract content that describes:

- The research aims regarding spontaneous hypertensive rats as OA models
- The methodology used to assess bone and meniscus changes
- The specific phenotypic findings related to metabolic syndrome-associated osteoarthritis
- The conclusions about using this animal model for OA research

If you could provide the complete abstract, I would be happy to create the concise 3-4 sentence summary you requested, translating the findings into plain language relevant for osteoarthritis phenotyping and musculoskeletal rehabilitation.

KNEE OSTEOARTHRITIS PHENOTYPES AND THEIR RELEVANCE FOR OUTCOMES: A SYSTEMATIC REVIEW.

This systematic review examined how researchers have identified different subgroups (phenotypes) of people with knee osteoarthritis and what characteristics are most important for distinguishing these groups. The authors reviewed 34 studies from multiple databases, focusing on how different patient characteristics relate to clinically important outcomes like pain and function.

The review found that several key factors consistently identify distinct knee osteoarthritis subgroups: pain sensitization, psychological distress, X-ray severity, body weight, muscle strength, inflammation levels, and other health conditions. Most studies used only single characteristics to define subgroups, though some combined multiple factors, and eight studies specifically looked at different patterns of how symptoms progress over time.

The findings suggest that people with knee osteoarthritis are not all the same and may need different treatment approaches based on their specific combination of symptoms, physical findings, and other characteristics. However, the authors noted significant inconsistency between studies in how subgroups were defined, and called for a more standardized framework to better identify these different osteoarthritis phenotypes, which could ultimately lead to more personalized physiotherapy and management strategies.

KNEE INTERNAL CONTACT FORCE IN A VARUS MALALIGNED PHENOTYPE IN KNEE OSTEOARTHRITIS (KOA).

This study aimed to investigate whether different knee osteoarthritis phenotypes based on alignment and cartilage damage patterns experience different internal joint forces during walking. Researchers analyzed 39 knee osteoarthritis patients classified into three subgroups (varus medial disease, varus generalized disease, and neutral alignment) plus 18 healthy controls, using computer modeling to estimate compression forces in the knee joint during walking.

The key finding was that patients with varus medial disease (those with inward-angled knees and cartilage damage mainly on the inner side) had significantly higher compression forces on the medial (inner) side of their knee compared to all other groups. Additionally, in this specific phenotype, the degree of knee malalignment was strongly related to the magnitude of these harmful forces, whereas this relationship didn't exist in the other patient groups.

These results suggest that patients with varus alignment and isolated medial cartilage damage represent a distinct biomechanical phenotype that experiences excessive loading on the inner knee compartment. For physiotherapy and management, this indicates that interventions targeting load redistribution, such as gait retraining, strengthening exercises, or orthotic devices, may be particularly beneficial for this specific subgroup of patients.

SOLUBLE BIOCHEMICAL MARKERS OF OSTEOARTHRITIS: ARE WE CLOSE TO USING THEM IN CLINICAL PRACTICE?

This review examined whether soluble biochemical markers (biomarkers) could improve osteoarthritis diagnosis and treatment beyond current X-ray-based methods. The authors reviewed existing research on biomarkers that can be measured in blood or other body fluids, focusing on their potential to detect joint changes and inflammation that X-rays cannot capture. The key finding is that combining patient information, advanced imaging, and carefully selected panels of biomarkers can identify distinct osteoarthritis subgroups (called "molecular endotypes") and separate patients who will progress rapidly from those with stable disease. This biomarker-based approach could enable physiotherapists and clinicians to provide more personalized treatments tailored to each patient's specific osteoarthritis type, potentially leading to better outcomes and more targeted rehabilitation strategies.

RESPONSE TO: 'SPONTANEOUS HYPERTENSIVE RAT EXHIBITS BONE AND MENISCUS PHENOTYPES OF OSTEOARTHRITIS: IS IT AN APPROPRIATE CONTROL FOR METS-ASSOCIATED OA?' BY CHAN AND WEN.

I notice that while you've provided a title for this research paper, the abstract is listed as "NA" (not available). Without the abstract content, I cannot provide a meaningful summary of the study's objective, methods, findings, or implications for osteoarthritis phenotyping and physiotherapy management.

To write the concise 3-4 sentence summary you've requested focusing on study objectives, key methods, phenotype findings, and management implications, I would need access to the actual abstract content. Could you please provide the abstract text for this paper about spontaneous hypertensive rats and their potential as a control model for metabolic syndrome-associated osteoarthritis?

OSTEOARTHRITIS: IN SEARCH OF PHENOTYPES.

I notice that only the title "OSTEOARTHRITIS: IN SEARCH OF PHENOTYPES" was provided, but the abstract is marked as "NA" (not available).

Without the abstract content, I cannot provide the specific details you've requested about the study objective, methods, findings regarding phenotypes/subgroups, or implications for management and physiotherapy.

To write the concise summary you need, I would require the actual abstract text. Could you please provide the abstract content so I can create an accurate 3-4 sentence summary focusing on the key elements you've outlined?

VARIOUS TYPES OF ARTHRITIS IN THE UNITED STATES: PREVALENCE AND AGE-RELATED TRENDS FROM 1999 TO 2014.

This study aimed to examine how the prevalence of different types of arthritis changed in the United States between 1999 and 2014. The researchers analyzed data from over 43,000 adults participating in national health surveys, using statistical methods to track trends over time across different demographic groups.

The key finding was that osteoarthritis (OA) prevalence more than doubled from 6.6% to 14.3%, while rheumatoid arthritis (RA) prevalence decreased from 5.9% to 3.8%. The OA increase occurred across all demographic groups studied, while the RA decline was most notable in men, non-Hispanic Black individuals, and people with low income or obesity.

These findings suggest that physiotherapists and healthcare providers should expect to see increasing numbers of patients with OA, particularly requiring strategies for prevention and management across diverse populations, while RA caseloads may be stabilizing or decreasing in certain demographic subgroups.

NA

This study aimed to characterize a specific subset of immune cells (IL-6-secreting CD4+ T cells) found in the infrapatellar fat pad of knee osteoarthritis patients and understand their role in joint inflammation. The researchers analyzed these T cells directly from patient tissue samples, examining their activation markers, cytokine production patterns, genetic signatures, and interactions with fat cells (adipocytes).

The key finding was that IL-6-producing CD4+ T cells represent a distinct, highly activated immune cell population that doesn't fit into conventional T cell categories, and these cells appear to be stimulated by interactions with adipocytes in the fat pad. The study revealed that fat cells can enhance IL-6 production by these T cells, suggesting a harmful cycle where fat tissue and immune cells promote inflammation in the osteoarthritic joint.

These findings suggest that osteoarthritis patients with significant infrapatellar fat pad involvement may represent a distinct inflammatory phenotype that could benefit from targeted anti-inflammatory treatments, and highlight the importance of addressing obesity and metabolic factors in osteoarthritis management and physiotherapy approaches.

SYMPTOMATIC COURSE OF FOOT OSTEOARTHRITIS PHENOTYPES: AN 18-MONTH PROSPECTIVE ANALYSIS OF COMMUNITY-DWELLING OLDER ADULTS.

This study aimed to track how symptoms change over 18 months in three different types (phenotypes) of foot osteoarthritis among 533 community-dwelling adults aged 50 and older. Researchers used postal surveys and X-rays to compare changes in pain and other symptoms across three groups: those with no/minimal foot OA, isolated big toe joint OA, and multiple joint foot OA. All three phenotypes showed small improvements in foot pain over 18 months, with pain levels remaining relatively stable (ranging from 4.0-5.1 on a 0-10 scale), and people with isolated big toe joint OA were nearly three times more likely to develop bunions. These findings suggest that mild-to-moderate foot OA symptoms remain fairly stable with usual care, which has important implications for designing clinical trials and setting realistic expectations for physiotherapy outcomes in this patient population.

THE IMPACT OF LIPID TYPES AND LIPOSOMAL FORMULATIONS ON OSTEOBLAST ADIPOSITY AND MINERALIZATION.

This laboratory study investigated how different types of lipids used in drug delivery systems affect bone-forming cells (osteoblasts), since fat accumulation in bone cells can harm bone health. Researchers tested various liposomal formulations containing different lipids on mouse osteoblasts, measuring cell survival, bone formation (mineralization), fat droplet formation, and inflammatory responses. The study found that positively-charged lipids were more toxic and inflammatory, while neutral lipids caused less fat accumulation and better maintained the cells' ability to form bone; importantly, formulations containing phosphatidylcholine (PC) showed anti-inflammatory effects. These findings suggest that PC-based liposomal drug delivery systems may be preferable for treating bone and joint conditions like osteoarthritis, potentially offering better outcomes with reduced harmful effects on bone health.

CLASSIFICATION OF PATIENTS WITH KNEE OSTEOARTHRITIS IN CLINICAL PHENOTYPES: DATA FROM THE OSTEOARTHRITIS INITIATIVE.

This study aimed to classify people with knee osteoarthritis into six distinct clinical phenotypes (minimal joint disease, malaligned biomechanical, chronic pain, inflammatory, metabolic syndrome, and bone/cartilage metabolism) to better understand the varied nature of the condition. The researchers used data from 599 patients in the Osteoarthritis Initiative database and applied predetermined criteria to categorize participants into these phenotypes through a three-step selection process. They successfully classified 84% of patients, with 20% showing features of multiple phenotypes (termed 'complex knee osteoarthritis'), and found that different phenotypes had distinct characteristics - for example, the chronic pain group was predominantly women (81%) while the minimal joint disease group had shorter disease duration. These findings suggest that personalized physiotherapy and management approaches could be developed based on a patient's specific phenotype, potentially leading to more targeted and effective treatments rather than using a one-size-fits-all approach.

IMPROVEMENT OF THE CHONDROCYTE-SPECIFIC PHENOTYPE UPON EQUINE BONE MARROW MESENCHYMAL STEM CELL DIFFERENTIATION: INFLUENCE OF CULTURE TIME, TRANSFORMING GROWTH FACTORS AND TYPE I COLLAGEN SIRNAS ON THE DIFFERENTIATION INDEX.

This study aimed to optimize a cell-based therapy technique for cartilage repair by improving how bone marrow stem cells are converted into cartilage cells (chondrocytes) in horses, which serves as a model for human osteoarthritis treatment. Researchers tested three key factors affecting stem cell conversion: culture time (14-42 days), different growth factor combinations, and genetic modification techniques to suppress unwanted collagen production. They found that longer culture times (28-42 days) combined with specific growth factors (BMP-2 and TGF-β1) and targeted genetic modifications produced more stable, cartilage-like cells with improved functional characteristics. These findings could lead to better cartilage repair therapies for both horses and humans with osteoarthritis, potentially offering new treatment options where current approaches focus mainly on symptom management rather than actual tissue repair.

ROLE OF IFT88 IN ICARIIN‑REGULATED MAINTENANCE OF THE CHONDROCYTE PHENOTYPE.

This study investigated how the protein IFT88 contributes to icariin's ability to maintain healthy cartilage cell characteristics, which is important for cartilage repair and tissue engineering. Researchers used laboratory cell cultures and a rat model of post-traumatic osteoarthritis to test icariin's effects on cartilage cells, examining cell growth, gene expression, and protein signaling pathways. The key finding was that icariin helps maintain the cartilage cell phenotype by increasing IFT88 protein levels through a specific cellular signaling pathway (ERK phosphorylation), which promotes the formation of cellular structures called primary cilia that are essential for proper cartilage function. These results suggest that icariin could potentially be developed as a therapeutic agent for cartilage repair in osteoarthritis, though this is still early-stage research focused on understanding basic cellular mechanisms rather than direct clinical applications for physiotherapy.

ALTERATIONS OF SUBCHONDRAL BONE PROGENITOR CELLS IN HUMAN KNEE AND HIP OSTEOARTHRITIS LEAD TO A BONE SCLEROSIS PHENOTYPE.

This study investigated whether abnormal bone-forming cells contribute to the bone sclerosis (thickening and hardening) commonly seen in osteoarthritis of the knee and hip. Researchers extracted and analyzed bone progenitor cells from sclerotic and non-sclerotic areas of osteoarthritic joints, comparing them to healthy bone cells through laboratory tests and animal implantation studies. They found that osteoarthritic bone cells had twice the bone-forming potential compared to healthy cells, but produced poorly mineralized bone tissue - explaining why osteoarthritic bone becomes thick but weak. These findings suggest that targeting dysfunctional bone-forming cells could be a new treatment approach for osteoarthritis, potentially informing rehabilitation strategies that consider bone quality alongside joint function.

KNEE PAIN AND THE USE OF VARIOUS TYPES OF FOOTWEAR-A REVIEW.

This review examined how different types of footwear affect knee pain in patients with osteoarthritis (OA) and patellofemoral pain (PFP). The authors reviewed existing literature on various specialized footwear and orthotic interventions, focusing on how these modify forces and loads on knee joints. The study identified two main knee pain phenotypes - OA and PFP - but found conflicting results across studies regarding footwear effectiveness, though there were enough positive findings to suggest potential benefits, particularly for knee OA. The findings suggest that specialized footwear could be considered as a cost-effective treatment option in physiotherapy and rehabilitation programs, though more research is needed to determine which specific footwear types work best for different patient subgroups.

CELECOXIB-MEDIATED REDUCTION OF PROSTANOID RELEASE IN HOFFA'S FAT PAD FROM DONORS WITH CARTILAGE PATHOLOGY RESULTS IN AN ATTENUATED INFLAMMATORY PHENOTYPE.

This study aimed to compare inflammatory patterns in Hoffa's fat pad (tissue behind the kneecap) between osteoarthritis patients and those with only cartilage damage, and to test whether the anti-inflammatory drug celecoxib could reduce inflammation in this tissue. Researchers analyzed inflammatory substances called prostanoids and gene expression patterns in fat pad samples from 17 osteoarthritis patients and 12 patients with cartilage defects, both with and without celecoxib treatment. The key finding was that osteoarthritis patients fell into two distinct subgroups - high and low inflammatory producers - with the high producers showing much greater release of inflammatory substances and more pro-inflammatory immune cell activity compared to patients with only cartilage damage. Celecoxib was most effective at reducing inflammation and shifting the tissue toward a healthier, anti-inflammatory state in patients who were initially high inflammatory producers, suggesting that identifying these inflammatory subgroups could help physiotherapists and clinicians better target anti-inflammatory treatments for knee osteoarthritis.

RADIOCARPAL DISLOCATIONS AND FRACTURE-DISLOCATIONS: INJURY TYPES AND LONG-TERM OUTCOMES.

This retrospective study aimed to analyze injury patterns and long-term outcomes in 41 patients with radiocarpal dislocations and fracture-dislocations, which are severe but rare wrist injuries. The researchers classified injuries using the Dumontier system and followed 13 patients for an average of 14 years, measuring range of motion, grip strength, pain, and functional scores.

The study identified that Type 2 injuries were much more common than Type 1, and while 6 patients developed osteoarthritis and required wrist fusion, most patients achieved good functional outcomes with 100° flexion-extension range, 86% grip strength compared to the uninjured side, and low pain scores.

For physiotherapy and management, the findings suggest that effective initial reduction and stabilization are crucial for preventing long-term complications, and that patients who achieve good reduction without associated fractures tend to have better outcomes and less risk of developing osteoarthritis requiring fusion surgery.

DIFFERENTIAL CONTRIBUTIONS OF SPECIMEN TYPES, CULTURING, AND 16S RRNA SEQUENCING IN DIAGNOSIS OF PROSTHETIC JOINT INFECTIONS.

**Study Summary:**

This study aimed to compare different diagnostic methods for detecting prosthetic joint infections (PJI) versus non-infectious failures in patients undergoing hip or knee revision surgery. Researchers collected multiple specimen types (joint fluid, tissue biopsies, swabs, and sonication fluid from prosthetic components) from 114 surgical cases and tested them using conventional 6-day cultures, extended 14-day cultures, and 16S rRNA gene sequencing. The key finding was that extended 14-day cultures of joint fluid, soft-tissue biopsies, and prosthetic component sonication fluid detected 93% of infections compared to only 65% with conventional tissue biopsy cultures, while 16S rRNA sequencing identified 83% of cases. These results suggest that using multiple specimen types with extended culture periods significantly improves PJI diagnosis, which could help orthopedic surgeons and physiotherapists better identify patients who need infection treatment versus those suitable for standard rehabilitation protocols after revision surgery.

THE PRO-INFLAMMATORY PHENOTYPE OF THE HUMAN NON-CLASSICAL MONOCYTE SUBSET IS ATTRIBUTED TO SENESCENCE.

This study aimed to understand why non-classical monocytes (a specific type of immune cell) are highly inflammatory despite having markers that should suppress inflammation. Researchers analyzed three monocyte subsets from human blood, measuring cellular aging markers like telomere length, oxidative stress, and inflammatory protein production. They discovered that non-classical monocytes show clear signs of cellular senescence (aging), which explains their pro-inflammatory behavior through a process called senescence-associated secretory phenotype (SASP). These findings suggest that age-related accumulation of senescent immune cells may contribute to inflammatory conditions like osteoarthritis, potentially opening new therapeutic targets for managing chronic inflammation in musculoskeletal diseases through anti-senescence approaches.

RECENT INSIGHTS INTO THE CONTRIBUTION OF THE CHANGING HYPERTROPHIC CHONDROCYTE PHENOTYPE IN THE DEVELOPMENT AND PROGRESSION OF OSTEOARTHRITIS.

This review aimed to examine how changes in cartilage cell (chondrocyte) behavior contribute to osteoarthritis development and progression, specifically focusing on when these cells adopt characteristics similar to those seen in bone formation processes. The authors conducted a literature review to analyze current knowledge about the molecular mechanisms that drive chondrocytes to change from their normal cartilage-maintaining role to a bone-forming phenotype during osteoarthritis. The key finding suggests that osteoarthritic cartilage undergoes cellular changes that resemble the natural bone development process (endochondral ossification), but the exact contribution of this process to disease progression remains unclear. Understanding these cellular transformations could lead to new regenerative treatment approaches that target the underlying biological mechanisms rather than just managing symptoms, potentially offering more effective alternatives to current physiotherapy and medical management strategies that primarily focus on slowing disease progression.

THE VALUE OF PHENOTYPES IN KNEE OSTEOARTHRITIS RESEARCH.

This review aimed to comprehensively describe the various phenotypes (subgroups) that can be used to categorize knee osteoarthritis patients for research purposes. The authors conducted a literature review and organized phenotypes into four main groups based on simple clinical assessments: demographics (including metabolic factors like obesity and diabetes), mechanical characteristics (joint shape, alignment, and injury history), associated musculoskeletal disorders (multiple joint involvement, spine problems), and knee-specific tissue features (involving cartilage, meniscus, bone, and pain location). The review identified numerous potential phenotype clusters, though many still require further validation through research studies. These phenotyping approaches could significantly improve osteoarthritis research and treatment by allowing clinicians and researchers to better categorize patients and potentially tailor rehabilitation strategies based on individual patient characteristics rather than using a one-size-fits-all approach.

MITOCHONDRIAL DNA VARIATION AND THE PATHOGENESIS OF OSTEOARTHRITIS PHENOTYPES.

This study examines how variations in mitochondrial DNA (mtDNA) contribute to different types and patterns of osteoarthritis development. The research focuses on mitochondria - the cell's energy factories - and how genetic differences in their DNA affect various cellular processes including inflammation, cell death, and the production of harmful molecules that can damage joints. The findings suggest that specific mtDNA variations influence distinct OA characteristics related to metabolism, inflammation, and aging, essentially creating different OA "fingerprints" or phenotypes in patients. These genetic variations could potentially be used as biomarkers to better diagnose OA subtypes and predict disease progression, which may help physiotherapists and clinicians develop more personalized treatment approaches based on a patient's specific genetic and metabolic profile.

MOLECULAR CHARACTERIZATION OF MESENCHYMAL STEM CELLS IN HUMAN OSTEOARTHRITIS CARTILAGE REVEALS CONTRIBUTION TO THE OA PHENOTYPE.

This study aimed to understand the role of mesenchymal stem cells (MSCs) found in osteoarthritis (OA) cartilage and whether they contribute to disease progression. Researchers created stable cell lines from human OA cartilage and analyzed their molecular characteristics and behavior compared to normal cartilage cells.

The study identified two distinct populations of MSCs in OA cartilage - one that preferentially develops into cartilage cells and another that tends to form bone cells. Importantly, both types of OA-MSCs showed higher levels of harmful proteins (COL10A1 and RUNX2) associated with cartilage breakdown compared to regular cartilage cells, and they released enzymes that can damage cartilage.

These findings suggest that rather than helping repair cartilage as hoped, these stem cells may actually contribute to cartilage destruction in OA, representing a specific disease phenotype. This research indicates that targeting these problematic stem cells could be a new therapeutic approach, potentially informing future treatments that physiotherapists and clinicians could use alongside exercise and other rehabilitation strategies.

FUNCTIONAL KNEE PHENOTYPES: A CALL FOR A MORE PERSONALISED AND INDIVIDUALISED APPROACH TO TOTAL KNEE ARTHROPLASTY?

I apologize, but I cannot provide a meaningful summary of this research paper because the abstract is listed as "NA" (not available).

Without the abstract content, I cannot determine:
- The specific study objectives or research questions
- The methods used to identify functional knee phenotypes
- The key findings about different patient subgroups
- The implications for personalizing total knee arthroplasty approaches

To provide the concise 3-4 sentence summary you requested focusing on phenotypes, management implications, and physiotherapy relevance, I would need access to the actual abstract content. If you could provide the abstract text, I would be happy to create the summary in plain language as requested.

PHENOTYPIC INSTABILITY OF CHONDROCYTES IN OSTEOARTHRITIS: ON A PATH TO HYPERTROPHY.

This review study aimed to examine how cartilage cells (chondrocytes) change their behavior and characteristics during osteoarthritis development. The authors analyzed existing research literature focusing on cellular changes, particularly DNA modifications and inflammatory signaling pathways that occur when healthy cartilage cells lose their normal stable state. The key finding is that osteoarthritis involves cartilage cells shifting from their normal maintenance role to a harmful "hypertrophic" state, where they produce degrading enzymes and abnormal cartilage components, ultimately leading to permanent cartilage damage. Understanding these cellular changes at the molecular level could help develop more targeted treatments and rehabilitation strategies that address the underlying biological processes driving osteoarthritis progression, rather than just managing symptoms.

STATE OF ART AND LIMITATIONS IN GENETIC ENGINEERING TO INDUCE STABLE CHONDROGENIC PHENOTYPE.

This review aimed to examine genetic engineering approaches for creating stable cartilage-producing cells to overcome current limitations in cartilage repair therapies. The authors analyzed various gene targets that promote cartilage regeneration or prevent cartilage breakdown, along with different methods to deliver these genes into various cell types including chondrocytes, stem cells, and joint lining cells. The research highlighted that while genetic manipulation shows promise for maintaining stable cartilage-producing cell characteristics, significant technical challenges and safety risks remain that limit clinical application. These findings suggest that gene therapy approaches for cartilage repair are still experimental, meaning current physiotherapy and rehabilitation strategies remain the primary evidence-based treatments for managing cartilage-related joint conditions like osteoarthritis.

DIGITAL BIOMARKERS OF SPINE AND MUSCULOSKELETAL DISEASE FROM ACCELEROMETERS: DEFINING PHENOTYPES OF FREE-LIVING PHYSICAL ACTIVITY IN KNEE OSTEOARTHRITIS AND LUMBAR SPINAL STENOSIS.

This study aimed to identify distinct physical activity patterns (phenotypes) in people with lumbar spinal stenosis (LSS) and knee osteoarthritis using accelerometer data from daily life. Researchers analyzed movement data from over 4,000 people (75 with LSS, 1,950 with knee OA, and 2,003 pain-free controls) using 42 novel features that characterize how people move throughout the day. The study successfully identified unique activity patterns for each condition, achieving 80% accuracy in distinguishing between people with LSS or knee OA versus healthy controls, and 72% accuracy in differentiating between the two conditions - with differences mainly seen in light and moderate activity levels rather than vigorous exercise. These findings suggest that wearable devices could help physiotherapists and clinicians develop more personalized activity prescriptions by identifying specific movement patterns associated with each condition, potentially leading to more targeted rehabilitation approaches.

ALTERED N-METHYL D-ASPARTATE RECEPTOR SUBUNIT EXPRESSION CAUSES CHANGES TO THE CIRCADIAN CLOCK AND CELL PHENOTYPE IN OSTEOARTHRITIC CHONDROCYTES.

This study investigated whether N-methyl-D-aspartate receptors (NMDAR) control the internal body clock and behavior of cartilage cells (chondrocytes) in osteoarthritis. Researchers compared chondrocytes from normal and osteoarthritic human cartilage, using various laboratory techniques to block or enhance different NMDAR components and measure changes in clock genes and cartilage-related markers.

The key finding was that osteoarthritic chondrocytes have disrupted circadian clocks and uniquely express a specific NMDAR subunit called GLUN2B, which normal cartilage cells do not have. When researchers blocked GLUN2B in osteoarthritic cells, it restored normal clock function and reduced harmful enzymes that break down cartilage, while blocking NMDAR in normal cells actually made them behave more like diseased cells.

These results suggest that osteoarthritis involves distinct cellular subgroups - normal chondrocytes without GLUN2B and pathological chondrocytes with GLUN2B expression. For physiotherapy and management, this research indicates that targeting NMDAR pathways, particularly GLUN2B, could potentially help restore normal cartilage cell function and reduce joint degeneration, though this would require development of specific therapeutic interventions.

DELETION OF AXIN1 IN CONDYLAR CHONDROCYTES LEADS TO OSTEOARTHRITIS-LIKE PHENOTYPE IN TEMPOROMANDIBULAR JOINT VIA ACTIVATION OF Β-CATENIN AND FGF SIGNALING.

This study aimed to investigate the role of the AXIN1 protein in temporomandibular joint (TMJ) osteoarthritis by examining what happens when this protein is removed from jaw cartilage cells in mice. Researchers used genetically modified mice where AXIN1 was deleted from cartilage cells at 2 months of age, then analyzed the TMJ tissues at 4 and 6 months using microscopy, tissue staining, and gene expression techniques. The main findings showed that mice without AXIN1 developed severe TMJ osteoarthritis-like changes including cartilage surface breakdown, vertical cracks, increased cartilage-destroying enzymes (MMP13, ADAMTS5), and abnormal cell death and growth patterns - essentially creating distinct disease phenotypes through two specific cellular signaling pathways (β-catenin and FGF signaling). These results suggest that AXIN1 deficiency represents a specific molecular subtype of TMJ osteoarthritis, which could inform targeted treatments for patients with similar genetic or molecular profiles, though direct physiotherapy implications require further research in human studies.

FATTY ACIDS AND OSTEOARTHRITIS: DIFFERENT TYPES, DIFFERENT EFFECTS.

This review examined how different types of fatty acids affect osteoarthritis development and symptoms, moving beyond the traditional view that obesity impacts joints only through increased mechanical loading. The authors systematically reviewed animal studies, human laboratory studies, and human intervention trials to compare the effects of omega-3 fatty acids, omega-6 fatty acids, saturated fats, and monounsaturated fats on joint inflammation, cartilage breakdown, and osteoarthritis symptoms. The findings revealed distinct patterns: omega-3 fatty acids consistently reduced inflammation, cartilage damage, and pain/dysfunction, while saturated and omega-6 fatty acids promoted harmful inflammatory processes and joint deterioration. These results suggest that dietary fatty acid composition could represent an important phenotyping factor for osteoarthritis patients, with omega-3 supplementation potentially offering a complementary treatment approach alongside traditional physiotherapy, though more robust human clinical trials are needed to establish definitive treatment guidelines.

DEEP PHENOTYPING OF OSTEOARTHRITIS: A STEP FORWARD.

I apologize, but I cannot provide a meaningful summary of this research paper because the abstract is listed as "NA" (not available).

To write an accurate summary focusing on the study objective, methods, findings regarding osteoarthritis phenotypes/subgroups, and implications for physiotherapy management, I would need access to the actual abstract content that describes the research methodology, results, and conclusions.

If you could provide the complete abstract text, I would be happy to create a concise 3-4 sentence summary in plain language that addresses all the key points you've requested regarding osteoarthritis phenotyping and its clinical implications.

DIFFERENTIATING KNEE PAIN PHENOTYPES IN OLDER ADULTS: A PROSPECTIVE COHORT STUDY.

This study aimed to identify distinct knee pain patterns in older adults and track how they develop over nearly 11 years. Researchers followed 963 people (average age 63) using questionnaires, MRI scans, and statistical analysis to group participants based on factors like emotional health, knee damage, body weight, and pain levels.

The analysis revealed three distinct knee pain groups: a "high emotional problems/low structural damage" group (25% of people), a "high structural damage/low emotional problems" group (20%), and a "low problems in both areas" group (55%). The emotional problems group consistently experienced the worst pain and most widespread pain throughout the study period, even compared to those with significant knee joint damage.

These findings suggest that physiotherapy and treatment approaches should be tailored differently for each group - with those having emotional factors potentially needing psychological support alongside physical treatments, while those with mainly structural problems may benefit more from joint-focused interventions.

HAND OSTEOARTHRITIS: CLINICAL PHENOTYPES, MOLECULAR MECHANISMS AND DISEASE MANAGEMENT.

This review aimed to provide a comprehensive overview of hand osteoarthritis (OA), examining its clinical presentations, underlying mechanisms, and current management approaches. The authors synthesized recent evidence from genetic studies, clinical trials, and advanced imaging research (including radiography, ultrasound, and MRI) conducted over the past 5 years. The review highlights that hand OA is a heterogeneous condition with multiple clinical phenotypes, affecting various joint tissues (bone, cartilage, ligaments, and synovium) and having multifactorial causes. These findings suggest that understanding the different subtypes of hand OA could lead to more personalized treatment approaches and new therapeutic targets, potentially improving management strategies for the pain, functional limitations, and daily activity restrictions that patients commonly experience.

PAIN SUSCEPTIBILITY PHENOTYPES IN THOSE FREE OF KNEE PAIN WITH OR AT RISK OF KNEE OSTEOARTHRITIS: THE MULTICENTER OSTEOARTHRITIS STUDY.

This study aimed to identify pain susceptibility phenotypes (PSPs) in older adults without knee pain but with or at risk of knee osteoarthritis, and determine which phenotypes predict future persistent knee pain. Researchers analyzed 852 participants using latent class analysis, examining factors like widespread pain, sleep quality, psychological factors, and pain sensitivity measures through quantitative sensory testing over 2 years. Four distinct phenotypes were identified, primarily characterized by different levels of pain sensitization - with one phenotype showing high pressure pain sensitivity and moderate facilitated temporal summation being twice as likely to develop persistent knee pain within 2 years. These findings suggest that targeting pain sensitization through physiotherapy interventions may help prevent the onset of persistent knee pain in at-risk individuals, offering a new approach beyond treating structural joint changes alone.

MULTILEVEL GLENOID MORPHOLOGY AND RETROVERSION ASSESSMENT IN WALCH B2 AND B3 TYPES.

This study aimed to determine whether glenoid retroversion (backward tilting of the shoulder socket) measurements vary at different heights in patients with specific types of shoulder arthritis (Walch B2 and B3 classifications). Researchers analyzed CT scans from 37 patients and measured retroversion angles at three different levels of the glenoid (upper, middle, and lower portions) using standardized techniques.

The key finding was that retroversion measurements remained consistent across all three glenoid levels, with very small differences between measurements (less than 2 degrees on average). The study demonstrated that glenoid version can be reliably measured at any level between 25-75% of the glenoid height, though the researchers recommend using the middle level (equator) as the standard reference point.

These findings have important implications for shoulder replacement surgery planning, as accurate measurement of glenoid retroversion is crucial for optimal implant positioning and long-term surgical outcomes, helping surgeons make more consistent preoperative assessments.

CLINICAL PERSPECTIVE ON PAIN AND PAIN PHENOTYPES IN OSTEOARTHRITIS.

This review examined the literature on pain phenotypes in knee osteoarthritis to understand why patients experience such different pain patterns despite similar joint damage. The authors analyzed evidence across multiple pain dimensions including structural/peripheral factors, psychological factors, genetic influences, environmental factors like obesity, and neurological mechanisms. The review found that pain in osteoarthritis is highly complex and individual, with poor correlation between joint damage seen on scans and actual pain severity - suggesting that genetic, psychological, environmental, and neurological factors all contribute to creating distinct pain phenotypes or subgroups of patients. These findings suggest that the current "one-size-fits-all" treatment approach may be ineffective, and that identifying specific pain phenotypes could lead to more personalized physiotherapy and management strategies, though more research is needed to validate these phenotypes in clinical practice.

BASIC CALCIUM PHOSPHATE CRYSTALS INDUCE OSTEOARTHRITIS-ASSOCIATED CHANGES IN PHENOTYPE MARKERS IN PRIMARY HUMAN CHONDROCYTES BY A CALCIUM/CALMODULIN KINASE 2-DEPENDENT MECHANISM.

This study investigated whether basic calcium phosphate (BCP) crystals, commonly found in osteoarthritic joints, can trigger disease-related changes in cartilage cells (chondrocytes). Researchers treated healthy human chondrocytes with BCP crystals for up to 48 hours and measured changes in key cellular markers and proteins. The results showed that BCP crystals caused chondrocytes to shift toward a harmful phenotype similar to that seen in osteoarthritis, including increased production of cartilage-degrading enzymes and inflammatory markers, through activation of a calcium-dependent signaling pathway (CaMK2). These findings suggest that BCP crystals may accelerate osteoarthritis progression, potentially identifying a subgroup of patients with crystal-associated disease who might benefit from targeted treatments that address calcium crystal formation or the cellular pathways they activate.

MOLECULAR TAXONOMY OF OSTEOARTHRITIS FOR PATIENT STRATIFICATION, DISEASE MANAGEMENT AND DRUG DEVELOPMENT: BIOCHEMICAL MARKERS ASSOCIATED WITH EMERGING CLINICAL PHENOTYPES AND MOLECULAR ENDOTYPES.

This review examined how biochemical markers can be used to identify distinct subtypes of osteoarthritis and guide personalized treatment approaches. The authors analyzed molecular biomarkers (particularly from synovial fluid) to understand disease mechanisms and classify patients into different groups based on their underlying biological processes. They identified four main osteoarthritis subtypes: inflammatory, bone remodeling, metabolic syndrome-related, and age-related senescent types, each with distinct molecular signatures and clinical characteristics. These findings suggest that physiotherapy and other treatments could be tailored to each patient's specific osteoarthritis subtype, potentially leading to more effective and personalized management strategies in clinical practice.

INJECTION OF ADIPOSE-DERIVED STROMAL CELLS IN THE KNEE OF PATIENTS WITH SEVERE OSTEOARTHRITIS HAS A SYSTEMIC EFFECT AND PROMOTES AN ANTI-INFLAMMATORY PHENOTYPE OF CIRCULATING IMMUNE CELLS.

This study investigated whether injecting patients' own fat-derived stem cells (adipose-derived stromal cells) into severely arthritic knees could reduce the body-wide inflammation associated with osteoarthritis. The researchers used detailed blood tests to track different types of immune cells in 18 patients before injection and at 1 week, 1 month, and 3 months afterward. They found that the stem cell injections promoted an anti-inflammatory immune profile throughout the body, with increases in regulatory T cells and transitional B cells (which help control inflammation) and decreases in classical monocytes (which promote inflammation) lasting at least 3 months. These findings suggest that stem cell therapy for osteoarthritis may work not just locally in the joint but also by calming down the whole-body inflammatory response, supporting its safety and indicating that patients with severe osteoarthritis might benefit from this systemic immune-modulating effect in addition to any local joint improvements.

THE PHENOTYPIC APPROACH TO OSTEOARTHRITIS: A LOOK AT METABOLIC SYNDROME-ASSOCIATED OSTEOARTHRITIS.

This review examines metabolic syndrome-associated osteoarthritis (Met-OA), a distinct subgroup of osteoarthritis patients characterized by obesity, metabolic disorders, and chronic inflammation. The authors analyzed existing literature to understand how obesity and metabolic syndrome components (diabetes, high blood pressure, abnormal cholesterol) contribute to joint damage through increased joint loading, inflammatory chemicals from fat tissue, gut bacteria changes, and muscle loss. The key finding is that Met-OA represents a specific osteoarthritis phenotype that affects not only weight-bearing joints like knees but also hands, and is driven by systemic inflammation rather than just mechanical wear and tear. For physiotherapy and management, this suggests that treating Met-OA patients requires addressing the underlying metabolic conditions and inflammation alongside traditional joint-focused treatments, potentially through weight management, cardiovascular exercise, and coordinated care with other healthcare providers to reduce both joint symptoms and cardiovascular risks.

MODEL-BASED PAIN AND FUNCTION OUTCOME TRAJECTORY TYPES FOR PATIENTS UNDERGOING KNEE ARTHROPLASTY: A SECONDARY ANALYSIS FROM A RANDOMIZED CLINICAL TRIAL.

This study aimed to identify distinct patterns of pain and function recovery following knee arthroplasty surgery and determine what factors predict poorer outcomes. Researchers analyzed data from 384 patients in a clinical trial, tracking their pain and function scores before surgery and at 2, 6, and 12 months afterward using statistical modeling to identify different recovery trajectories. The analysis revealed two main recovery patterns - "good" and "poor" - for both pain and function, with approximately 18% of patients following the poor trajectory characterized by persistent problems after surgery. Key factors predicting poor outcomes included pain catastrophizing (tendency to focus on and magnify pain), having pain in multiple body areas, low income, higher baseline pain levels, and younger age, suggesting that targeted pre-surgical screening and tailored physiotherapy interventions could help identify and support patients at higher risk for suboptimal recovery.

MIDFOOT OSTEOARTHRITIS: POTENTIAL PHENOTYPES AND THEIR ASSOCIATIONS WITH DEMOGRAPHIC, SYMPTOMATIC AND CLINICAL CHARACTERISTICS.

This study aimed to identify different subtypes (phenotypes) of midfoot osteoarthritis based on which joints are affected and determine their associated characteristics in 533 adults over 50 with foot pain. Researchers used X-rays to classify participants into groups based on joint involvement patterns (medial midfoot, central midfoot, or both areas) and assessed their symptoms, foot structure, and function through questionnaires and clinical examinations. The study found three potential phenotypes, but only people with osteoarthritis affecting both medial and central midfoot areas showed distinct characteristics including higher pain scores, specific pain location on top of the foot, hallux valgus (bunions), flatter feet, and reduced joint mobility. These findings suggest that physiotherapists may need to focus on comprehensive foot structure and mobility assessment particularly for patients with widespread midfoot osteoarthritis, though the overlapping symptoms between phenotypes indicate that individualized rather than phenotype-specific treatment approaches may be more appropriate.

SIMVASTATIN PROMOTES RESTORATION OF CHONDROCYTE MORPHOLOGY AND PHENOTYPE.

This study investigated whether simvastatin (a cholesterol-lowering drug) could help restore the normal characteristics of cartilage cells (chondrocytes) that had lost their typical properties, and explored the biological mechanism behind this effect. Researchers tested simvastatin on different types of cartilage cells, including cells from osteoarthritic human knees, and measured changes in cell shape, gene expression, and production of cartilage-specific proteins. The key finding was that simvastatin successfully restored healthy chondrocyte characteristics across all cell types, increasing production of important cartilage markers like SOX9 and collagen type II while reducing harmful fibrotic markers. The mechanism worked through blocking protein modification pathways (specifically prenylation) rather than through cholesterol reduction, suggesting simvastatin might offer a novel therapeutic approach for treating cartilage degeneration in osteoarthritis by helping damaged cartilage cells regain their normal function.

DISTINCT DEGENERATIVE PHENOTYPE OF ARTICULAR CARTILAGE FROM KNEES WITH MENISCUS TEAR COMPARED TO KNEES WITH OSTEOARTHRITIS.

This study aimed to compare gene expression patterns in knee cartilage from patients with meniscus tears versus end-stage osteoarthritis to identify distinct disease phenotypes. Researchers used advanced genetic analysis techniques to examine cartilage samples from 10 patients undergoing meniscus surgery and 10 patients receiving total knee replacements, finding 81 genes that were expressed differently between the two groups.

The results revealed two distinct patterns: cartilage from end-stage osteoarthritis knees showed increased immune response and inflammatory gene activity, while cartilage from meniscus tear patients displayed genes related to cartilage repair, development, and cellular energy production. This suggests that knees with meniscus tears represent an earlier stage of joint degeneration with active repair processes, whereas end-stage osteoarthritis involves predominantly inflammatory destruction.

These findings indicate that patients with meniscus tears and those with advanced osteoarthritis may require different treatment approaches, with meniscus tear patients potentially benefiting more from interventions that support the body's natural repair mechanisms rather than anti-inflammatory treatments alone.

OSTEOARTHRITIS PHENOTYPES AND NOVEL THERAPEUTIC TARGETS.

This review examines why drug trials for osteoarthritis (OA) treatments have repeatedly failed and explores how identifying distinct OA phenotypes could improve treatment success. The authors analyzed current research on OA heterogeneity using advanced imaging techniques like MRI, biochemical markers, and clinical trial data to identify different patient subgroups based on bone/cartilage changes, inflammation patterns, and pain characteristics. The key finding is that OA patients fall into distinct phenotypes with different underlying disease mechanisms, and treating all patients the same way likely explains why drug trials have failed. For physiotherapy and clinical management, this suggests that identifying a patient's specific OA phenotype using imaging, blood markers, and clinical features could lead to more personalized and effective treatment approaches rather than using one-size-fits-all interventions.

EVIDENCE SYNTHESIS OF TYPES AND INTENSITY OF THERAPEUTIC LAND-BASED EXERCISES TO REDUCE PAIN IN INDIVIDUALS WITH KNEE OSTEOARTHRITIS.

This evidence synthesis aimed to identify the most effective types, durations, and frequencies of land-based exercises for reducing pain in knee osteoarthritis patients. The researchers analyzed 55 randomized controlled trials comparing various exercise interventions to non-exercise control groups, extracting data on exercise types, program parameters, and pain outcomes. The study found that strengthening, proprioception, and aerobic exercises all significantly reduced pain, with strengthening exercises showing the most substantial evidence base. For clinical practice, the findings suggest that physiotherapists should prescribe exercises three times per week for 8-11 or 12-15 week periods to achieve optimal pain reduction in knee osteoarthritis patients, providing a practical evidence-based framework for treatment planning.

STRESS-ACTIVATED MIR-204 GOVERNS SENESCENT PHENOTYPES OF CHONDROCYTES TO PROMOTE OSTEOARTHRITIS DEVELOPMENT.

This study aimed to investigate how cellular aging (senescence) in cartilage cells contributes to osteoarthritis development, specifically focusing on a molecule called miR-204. The researchers used laboratory experiments with cartilage cells and animal models to examine how miR-204 affects cartilage breakdown and repair processes. They found that miR-204 levels are significantly elevated in osteoarthritic cartilage and acts as a key driver of cartilage deterioration by blocking the production of protective cartilage components while promoting inflammatory responses that damage joints. These findings suggest that targeting miR-204 or the cellular senescence pathway could offer new therapeutic approaches for osteoarthritis treatment, potentially informing future rehabilitation strategies that address the underlying molecular causes of cartilage breakdown rather than just symptoms.

PHENOTYPING OF HIP-KNEE-ANKLE ANGLE IN YOUNG NON-OSTEOARTHRITIC KNEES PROVIDES BETTER UNDERSTANDING OF NATIVE ALIGNMENT VARIABILITY.

This study aimed to better understand the natural variation in knee alignment by analyzing 3D CT images of 308 healthy knees in young adults (ages 16-45) and developing a new classification system based on alignment patterns. The researchers measured the hip-knee-ankle angle (HKA) using specialized 3D planning software and created distinct phenotypes representing 3-degree increments of alignment, each covering a ±1.5° range around specific mean values.

The findings revealed significant variability in normal knee alignment (ranging from 172.6° varus to 187.1° valgus) with gender differences, and identified that the most common phenotype in both men and women was neutral alignment (36.4%), though men showed more varus tendency while women leaned more toward valgus alignment.

This phenotype-based classification system provides a more precise alternative to the oversimplified traditional categories (neutral/varus/valgus), which could help clinicians better understand individual patient alignment patterns and potentially guide more personalized treatment approaches in knee rehabilitation and surgical planning.

A MACHINE LEARNING APPROACH TO KNEE OSTEOARTHRITIS PHENOTYPING: DATA FROM THE FNIH BIOMARKERS CONSORTIUM.

This study aimed to use machine learning techniques to identify distinct knee osteoarthritis phenotypes based on disease progression patterns over 48 months. Researchers analyzed data from 597 individuals using advanced statistical methods to compare "progressors" (those with both radiographic joint space narrowing and increased pain) versus "non-progressors" (those with neither outcome), examining 73 baseline variables including MRI findings, clinical measures, and biochemical markers.

The analysis successfully distinguished between progression phenotypes, with MRI-based variables showing stronger associations than demographic or biochemical factors. Key features associated with non-progression included baseline WOMAC pain scores, lateral meniscal extrusion, and certain collagen markers, while progression was linked to bone marrow lesions, osteophytes, medial meniscal extrusion, and specific collagen breakdown markers.

These findings suggest that MRI structural features are particularly important for predicting osteoarthritis progression phenotypes, which could help physiotherapists and clinicians identify patients most likely to benefit from specific interventions and tailor treatment approaches based on individual progression risk profiles.

CHARACTERIZATION OF SYNOVIAL FLUID METABOLOMIC PHENOTYPES OF CARTILAGE MORPHOLOGICAL CHANGES ASSOCIATED WITH OSTEOARTHRITIS.

This study aimed to identify different osteoarthritis (OA) subtypes by analyzing the chemical composition of joint fluid from 75 donors at various disease stages. Researchers used advanced laboratory techniques to measure metabolites (chemical compounds) in synovial fluid from healthy joints, early OA, and late OA cases. The analysis revealed distinct metabolic patterns between disease stages and identified specific OA subgroups characterized by either increased inflammation, oxidative stress (cellular damage), or structural joint breakdown. These findings suggest that OA patients could be categorized into different subtypes based on their joint fluid chemistry, potentially allowing physiotherapists and clinicians to develop more personalized treatment approaches targeting the specific underlying mechanisms driving each patient's condition.

DIFFERENT PHENOTYPES OF OSTEOARTHRITIS IN THE LUMBAR SPINE REFLECTED BY DEMOGRAPHIC AND CLINICAL CHARACTERISTICS: THE JOHNSTON COUNTY OSTEOARTHRITIS PROJECT.

This study aimed to identify different types (phenotypes) of osteoarthritis in the lower back by examining how patient characteristics relate to spine and facet joint arthritis patterns. Researchers analyzed data from 1,793 participants in the Johnston County Osteoarthritis Project, categorizing them into four groups based on whether they had spine arthritis, facet joint arthritis, both, or neither, then used statistical models to identify associated demographic and clinical factors. The study found distinct patterns: African Americans were less likely to have facet joint arthritis, women and people with higher body weight were more prone to facet joint arthritis, knee arthritis was linked to all spine arthritis types, while back injuries were specifically associated only with spine arthritis. These findings suggest that lower back arthritis isn't a single condition but includes different subtypes that may require tailored physiotherapy approaches - for example, focusing on weight management for facet joint problems or injury-specific rehabilitation for spine arthritis following back trauma.

INTRACELLULAR IRON UPTAKE IS FAVORED IN HFE-KO MOUSE PRIMARY CHONDROCYTES MIMICKING AN OSTEOARTHRITIS-RELATED PHENOTYPE.

This study investigated how iron overload affects cartilage cells (chondrocytes) in mice with HFE gene mutations, which cause hereditary hemochromatosis - a condition linked to increased osteoarthritis risk. Researchers compared chondrocytes from normal mice and HFE-knockout mice when exposed to high iron concentrations, measuring markers of cartilage breakdown and iron metabolism. Both cell types developed osteoarthritis-like characteristics when exposed to excess iron, including increased production of cartilage-degrading enzymes and reduced protective cartilage matrix, but HFE-knockout cells showed greater iron uptake and more severe cartilage breakdown. These findings suggest that patients with hereditary hemochromatosis may represent a distinct osteoarthritis phenotype requiring specialized management approaches that address both iron overload and joint protection through targeted physiotherapy and potentially iron-reduction therapies.

HYPERPHYSIOLOGICAL COMPRESSION OF ARTICULAR CARTILAGE INDUCES AN OSTEOARTHRITIC PHENOTYPE IN A CARTILAGE-ON-A-CHIP MODEL.

This study aimed to develop a laboratory model that could better replicate osteoarthritis (OA) development for testing potential new treatments. The researchers created a "cartilage-on-a-chip" device that applies controlled mechanical compression to 3D cartilage tissue samples, testing whether excessive compression (30% strain) could trigger OA-like changes. They found that this high level of compression successfully induced an OA phenotype, characterized by increased tissue breakdown, inflammation, cell enlargement (hypertrophy), and gene expression patterns similar to those seen in actual OA patients. This model could be valuable for screening new disease-modifying OA drugs and may help physiotherapists and clinicians better understand how mechanical loading contributes to OA progression, potentially informing exercise prescription and joint protection strategies.

SYNOVIAL FLUID BIOMARKERS ASSOCIATED WITH OSTEOARTHRITIS SEVERITY REFLECT MACROPHAGE AND NEUTROPHIL RELATED INFLAMMATION.

This study aimed to identify synovial fluid biomarkers that characterize people with an inflammatory type of knee osteoarthritis (OA). Researchers analyzed 47 different inflammatory molecules in synovial fluid from 48 knees and compared these with imaging measures of joint inflammation, X-ray severity, and symptom levels. They found six key biomarkers (sVCAM-1, sICAM-1, TIMP-1, VEGF, MMP-3, and MCP-1) that were strongly linked to worse inflammation, more severe joint damage, and greater symptoms - all connected to activated immune cells called macrophages and neutrophils. These findings suggest there is a distinct "inflammatory" subgroup of OA patients who could potentially benefit from targeted anti-inflammatory treatments, helping physiotherapists and clinicians identify which patients might need different management approaches focused on controlling inflammation rather than just mechanical factors.

THE ROLE OF CHONDROCYTE MORPHOLOGY AND VOLUME IN CONTROLLING PHENOTYPE-IMPLICATIONS FOR OSTEOARTHRITIS, CARTILAGE REPAIR, AND CARTILAGE ENGINEERING.

This review examined how the size and shape of cartilage cells (chondrocytes) control their behavior and function, which has important implications for understanding osteoarthritis and developing cartilage repair strategies. The researchers used advanced microscopy techniques to visualize individual chondrocytes within cartilage tissue, revealing significant differences in cell size, shape, and organization between healthy and mildly damaged cartilage. They found that chondrocytes in early osteoarthritis show distinct changes including increased cell volume, development of cellular projections, and clustering together - indicating these cells are changing from their normal healthy state to problematic forms that produce weaker cartilage. These findings suggest that monitoring and potentially controlling chondrocyte size and shape could lead to new treatment approaches for preventing cartilage breakdown in osteoarthritis and improving cartilage repair techniques, which could inform physiotherapy strategies aimed at maintaining joint health and function.

MOLECULAR PHENOTYPING OF THE SURFACEOME OF MIGRATORY CHONDROPROGENITORS AND MESENCHYMAL STEM CELLS USING BIOTINYLATION, GLYCOCAPTURE AND QUANTITATIVE LC-MS/MS PROTEOMIC ANALYSIS.

This study aimed to identify and compare cell surface proteins (the "surfaceome") between two types of stem cells relevant to cartilage repair: bone marrow mesenchymal stem cells (MSCs) and chondrogenic progenitor cells (CPCs) derived from osteoarthritic knee cartilage. The researchers used advanced laboratory techniques including biotinylation, glycocapture, and mass spectrometry to analyze the surface proteins of these cells. They identified 1,256 proteins total, with 791 (63%) being cell surface or related proteins, creating the first comprehensive comparison of surface proteins between these two cell types. These findings could help researchers better understand how cartilage cells change during osteoarthritis development and may lead to improved identification and use of these therapeutically promising cells for cartilage repair treatments.

A TRADITIONAL HIP IMPLANT IS AS EFFECTIVE AS NEWER TYPES FOR PEOPLE OVER 65.

I cannot provide a proper summary based on the information provided. The text appears to be a header or citation information rather than a complete abstract with study details.

To write an effective summary focusing on osteoarthritis phenotyping and rehabilitation implications, I would need:
- The actual study abstract describing methods, patient populations, and outcomes
- Information about any patient subgroups or phenotypes studied
- Results comparing implant effectiveness
- Details about rehabilitation protocols or physiotherapy considerations

If you could provide the full abstract, I'd be happy to create a concise summary addressing the four key areas you've requested (study objective, methods, phenotype findings, and management implications).

FRACTURE TYPES AFFECT CLINICAL OUTCOMES OF PATIENTS MANAGED WITHIN THE FRACTURE LIAISON AND OSTEOPOROSIS MEDICATION MANAGEMENT SERVICES.

This study examined how different fracture types affect clinical outcomes in 974 patients receiving fracture liaison and osteoporosis medication management services. Researchers grouped participants by fracture type (hip fracture only, vertebral fracture only, both hip and vertebral fractures, or neither) and tracked one-year mortality, refractures, and falls using statistical analyses. The study identified distinct patient phenotypes, with hip fracture patients being oldest with lowest body weight and highest fracture risk, while those with both hip and vertebral fractures had the worst outcomes for refractures and falls despite treatment. These findings suggest that fracture type should guide risk stratification and management intensity, with patients having multiple fracture types (especially hip plus vertebral) requiring more aggressive monitoring and potentially enhanced rehabilitation programs to prevent future fractures and falls.

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This study aimed to investigate the functional characteristics of a specific subset of immune cells called CD56⁺CD16⁻ natural killer (NK) cells in osteoarthritis (OA) patients compared to healthy individuals. The researchers analyzed blood samples from both groups, measuring the proportion of these NK cells and testing their ability to produce various proteins and regulate other immune cells through laboratory experiments.

The key finding was that OA patients had more CD56⁺CD16⁻ NK cells in their blood, and these cells showed an altered immune profile - they produced significantly more IFN-γ (a pro-inflammatory protein) but less granzyme and perforin (proteins involved in immune regulation). Additionally, these NK cells from OA patients were less effective at controlling the activation of T cells (another type of immune cell) and actually promoted more inflammatory responses.

These results suggest that OA patients may have a distinct immune system phenotype characterized by dysfunctional NK cells that contribute to chronic inflammation rather than helping to resolve it. This immune dysfunction could represent a potential target for future OA treatments, though the findings don't directly translate to immediate physiotherapy implications, as they focus on underlying biological mechanisms rather than movement-based interventions.

IDENTIFICATION OF PATHOLOGICAL RA ENDOTYPES USING BLOOD-BASED BIOMARKERS REFLECTING TISSUE METABOLISM. A RETROSPECTIVE AND EXPLORATIVE ANALYSIS OF TWO PHASE III RA STUDIES.

This study aimed to identify distinct rheumatoid arthritis (RA) patient subgroups using blood-based biomarkers that reflect joint tissue breakdown and metabolism. Researchers analyzed blood samples from 705 RA patients across two clinical trials, measuring seven different biomarkers related to cartilage degradation, bone turnover, tissue breakdown, inflammation, and immune cell activity, then used statistical clustering to group patients with similar biomarker patterns.

The analysis identified five distinct RA subgroups: two "high activity" groups with elevated tissue breakdown (one with particularly high immune activity), one "average" group with moderate biomarker levels, and two "low activity" groups (one specifically characterized by high bone turnover). Importantly, these subgroups showed different disease progression patterns over time, with significant differences in joint damage scores at one year.

These findings suggest that RA patients can be categorized into metabolically distinct subgroups based on which tissues are most affected and how active the disease process is. This approach could potentially help physiotherapists and clinicians tailor treatments more precisely—for example, focusing on bone health interventions for the high bone turnover subgroup or more intensive joint protection strategies for the high tissue breakdown groups.

VELVET ANTLER POLYPEPTIDE PARTIALLY RESCUE FACET JOINT OSTEOARTHRITIS-LIKE PHENOTYPE IN ADULT Β-CATENIN CONDITIONAL ACTIVATION MICE.

This study aimed to test whether velvet antler polypeptide (VAP) could treat facet joint osteoarthritis using genetically modified mice that develop arthritis-like changes in their spine joints. The researchers used mice engineered to over-express β-catenin (a protein involved in joint degeneration) and treated them with VAP, then analyzed joint structure using micro-CT scans, tissue examination, and molecular markers. VAP treatment partially improved the osteoarthritis-like changes by reducing bone spur formation, preserving cartilage area, decreasing harmful β-catenin levels, and reducing enzymes that break down cartilage (MMP13, ADAMTS4, and ADAMTS5). These findings suggest VAP could potentially be developed as a treatment for facet joint osteoarthritis, though this animal model research would need translation to human studies before considering clinical applications in physiotherapy or rehabilitation settings.

BIOMARKERS OF CARDIOVASCULAR RISK ACROSS PHENOTYPES OF OSTEOARTHRITIS.

This study examined whether different types of osteoarthritis (OA) are linked to cardiovascular disease risk by comparing joint damage scores with blood vessel stiffness measurements in 366 people with OA. Researchers used ultrasound and X-rays to assess joint damage in hands, hips, and knees, then grouped patients into three categories: isolated hand OA (42%), isolated lower limb OA (30%), and generalized OA affecting multiple joints (27%). The key finding was that hand bone spurs (osteophytes) were associated with increased arterial stiffness, and all OA types showed higher central blood pressure compared to healthy controls from two comparison groups. These results suggest that people with OA, particularly those with hand involvement, may need cardiovascular risk monitoring and management as part of their overall care, highlighting the importance of a holistic approach in physiotherapy and medical management beyond just treating joint symptoms.

CORRELATION BETWEEN SENESCENCE-ASSOCIATED SECRETORY PHENOTYPES FACTORS IN SYNOVIAL FLUID AND SERUM AND STRUCTURAL CHANGES IN OSTEOARTHRITIS.

I apologize, but I cannot provide a summary of this research study because the abstract is listed as "NA" (not available).

To write an accurate summary focusing on the study objective, methods, phenotype findings, and physiotherapy implications, I would need access to the actual abstract content that describes:
- The study's purpose and research questions
- The methodology and participant characteristics
- The specific senescence-associated secretory phenotype (SASP) factors measured
- The correlation results between synovial fluid/serum markers and structural changes
- The clinical implications of any identified osteoarthritis subgroups

If you could provide the complete abstract, I would be happy to create the requested 3-4 sentence summary in plain language focusing on the phenotyping and rehabilitation aspects.

EFFICACY AND SAFETY OF THE FIRST-IN-CLASS IMIDAZOLINE-2 RECEPTOR LIGAND CR4056 IN PAIN FROM KNEE OSTEOARTHRITIS AND DISEASE PHENOTYPES: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2 TRIAL.

This study tested whether a new pain medication called CR4056 could effectively treat knee osteoarthritis pain in different patient subgroups. The researchers conducted a 14-day randomized controlled trial with 213 patients, comparing CR4056 (given at different doses for men and women) against placebo, and specifically analyzed results in pre-defined osteoarthritis phenotypes including metabolic, neuropathic, and inflammatory subtypes.

The medication showed significant pain reduction in men and particularly strong benefits in overweight patients (BMI ≥27.5) representing the "metabolic" osteoarthritis phenotype, with pain improvements of 12-18 points compared to placebo. However, there were too few patients with neuropathic or inflammatory phenotypes to draw meaningful conclusions about these subgroups.

These findings suggest that osteoarthritis patients, especially those who are overweight, may respond differently to certain pain treatments, supporting the importance of personalized approaches in physiotherapy and medical management based on patient characteristics like body weight and metabolic factors.

COPPER-INCORPORATED BIOACTIVE GLASS-CERAMICS INDUCING ANTI-INFLAMMATORY PHENOTYPE AND REGENERATION OF CARTILAGE/BONE INTERFACE.

This study aimed to develop and test copper-incorporated bioactive glass-ceramic (Cu-BGC) scaffolds as a treatment for osteoarthritis by targeting both cartilage damage and inflammatory responses. Researchers used 3D-printing to create the scaffolds and tested them on cells in the lab and in animal models with cartilage defects. The key finding was that copper release from the scaffolds promoted an anti-inflammatory phenotype in immune cells (macrophages) while enhancing cartilage cell growth and maturation, leading to better healing of both cartilage and underlying bone compared to control treatments. These results suggest that copper-containing biomaterial scaffolds could offer a promising surgical treatment option for osteoarthritis patients with cartilage defects, potentially reducing inflammation while promoting tissue regeneration at the critical cartilage-bone interface.

SKELETAL PHENOTYPE/GENOTYPE IN PROGRESSIVE PSEUDORHEUMATOID CHONDRODYSPLASIA.

This study aimed to characterize the clinical and genetic features of progressive pseudorheumatoid chondrodysplasia (PPRC) in seven patients ranging from children (ages 9-17) to adults (ages 25-40). The researchers conducted detailed clinical examinations, skeletal imaging, and genetic testing through sequencing of the WISP3 gene to confirm diagnosis and understand disease patterns.

The study identified distinct phenotypic features including early joint pain, walking difficulties, spine deformities with flattened vertebrae, hip joint deterioration, and joint swelling - findings that were often initially misdiagnosed as juvenile rheumatoid arthritis or muscle disorders. Two specific loss-of-function mutations in the WISP3 gene were identified as the genetic cause.

For physiotherapy and management, this research emphasizes the importance of recognizing PPRC's unique clinical presentation early to avoid inappropriate treatments, and suggests that rehabilitation approaches should focus on addressing the progressive joint stiffness, abnormal spine mechanics, and mobility limitations that characterize this genetic condition rather than treating it as inflammatory arthritis.

REGULATION OF THE INFLAMMATORY SYNOVIAL FIBROBLAST PHENOTYPE BY METASTASIS-ASSOCIATED LUNG ADENOCARCINOMA TRANSCRIPT 1 LONG NONCODING RNA IN OBESE PATIENTS WITH OSTEOARTHRITIS.

This study aimed to identify long noncoding RNAs (lncRNAs) that contribute to increased inflammation in synovial fibroblasts from obese patients with osteoarthritis compared to normal-weight patients. Researchers collected synovial tissue from patients with hip OA (both normal-weight and obese) and controls, then used RNA sequencing and laboratory experiments to analyze inflammatory markers and lncRNA expression patterns.

The key finding was that synovial fibroblasts from obese OA patients showed a distinctly inflammatory phenotype, producing 3-fold higher levels of inflammatory proteins (IL-6 and CXCL8) compared to normal-weight OA patients. The researchers identified MALAT1 as a specific lncRNA that was significantly elevated in obese OA patients and appeared to regulate this inflammatory response - when MALAT1 was experimentally reduced, inflammation decreased and cell proliferation was inhibited.

These findings suggest that obesity creates a more inflammatory subtype of osteoarthritis through specific molecular pathways, which could help explain why obese patients often experience more severe joint inflammation and may require different treatment approaches targeting these inflammatory mechanisms.

ELEVATED LEVELS OF 15-LIPOXYGENASE-1 CONTRIBUTE TO THE ABNORMAL PHENOTYPES OF OSTEOBLASTS IN HUMAN OSTEOARTHRITIS.

This study investigated how the enzyme 15-lipoxygenase-1 (15-LOX-1) contributes to abnormal bone cell behavior in osteoarthritis. Researchers used laboratory techniques to measure 15-LOX-1 levels in bone samples from osteoarthritis patients and conducted cell culture experiments where they either blocked or increased 15-LOX-1 activity in bone-forming cells (osteoblasts). The findings revealed that osteoarthritis patients have elevated 15-LOX-1 levels, which disrupts normal cellular recycling processes (autophagy) and leads to overactive osteoblasts that produce excessive bone proteins, contributing to the bone thickening seen beneath damaged cartilage. These results suggest that targeting 15-LOX-1 or the cellular pathways it affects could offer new treatment approaches for managing osteoarthritis, potentially through therapies that restore normal bone cell function rather than just addressing symptoms.

SENESCENT SYNOVIAL FIBROBLASTS ACCUMULATE PREMATURELY IN RHEUMATOID ARTHRITIS TISSUES AND DISPLAY AN ENHANCED INFLAMMATORY PHENOTYPE.

This study aimed to investigate how cellular senescence (aging) affects inflammation in joint tissues from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Researchers examined senescence markers in synovial tissues from patients of different ages and tested how senescent cells respond to inflammatory stimuli in laboratory cultures. The key finding was that RA patients accumulate senescent (aged) synovial cells prematurely compared to healthy individuals, and these senescent cells produce significantly higher levels of inflammatory molecules when stimulated. These results suggest that targeting senescent cells with specific drugs (senolytics) could be a new treatment approach for managing joint inflammation, particularly in RA, by reducing the excessive inflammatory response that contributes to joint damage and symptoms.

BIALLELIC VARIANTS P.ARG1133CYS AND P.ARG1379CYS IN COL2A1: FURTHER DELINEATION OF PHENOTYPIC SPECTRUM OF RECESSIVE TYPE 2 COLLAGENOPATHIES.

This study aimed to expand understanding of recessive type 2 collagenopathies by investigating two families with rare biallelic (double) variants in the COL2A1 gene. The researchers analyzed genetic variants and clinical features in six patients from four families with homozygous mutations affecting collagen type 2 production. They identified two distinct skeletal dysplasia phenotypes of intermediate severity, both causing spondylo-epimetaphyseal dysplasia but with significant variation in short stature severity and involvement of different bone regions (spine, growth plates, and joint surfaces). These findings suggest that patients with these rare genetic subtypes may require individualized rehabilitation approaches based on their specific pattern of skeletal involvement, with physiotherapy focusing on the particular combination of spinal, joint, and growth-related issues present in each case.

CONTRIBUTION OF ADIPOCYTE PRECURSORS IN THE PHENOTYPIC SPECIFICITY OF INTRA-ARTICULAR ADIPOSE TISSUES IN KNEE OSTEOARTHRITIS PATIENTS.

This study investigated whether fat cell precursors (preadipocytes) from different locations in the knee joint contribute to distinct inflammatory patterns in osteoarthritis patients. Researchers isolated these precursors from fat pads inside the knee joint and compared them to those from subcutaneous fat, then tested their ability to develop into mature fat cells and their inflammatory responses to stimulation.

The key finding was that preadipocytes from intra-articular fat had a unique "dual personality" - they were normally less inflammatory than subcutaneous fat precursors, but showed much stronger inflammatory responses when exposed to joint inflammation signals. These intra-articular precursors also had greater capacity to become mature fat cells and expressed different developmental markers.

This suggests that osteoarthritis patients may have distinct fat tissue phenotypes within their joints that could amplify inflammation once the disease process begins. For physiotherapy and management, this highlights the importance of controlling joint inflammation early, as the fat pads inside arthritic knees may act as amplifiers of inflammatory responses rather than protective cushions.

RISK OF KNEE OSTEOARTHRITIS AFTER DIFFERENT TYPES OF KNEE INJURIES IN YOUNG ADULTS: A POPULATION-BASED COHORT STUDY.

This Swedish population-based study aimed to determine how different types of knee injuries in young adults (aged 25-34) affect the risk of developing knee osteoarthritis later in life. Researchers followed 149,288 people for up to 19 years, comparing 5,247 individuals with knee injuries to 142,825 without injuries, and analyzed eight specific injury types using healthcare registry data.

The study revealed that young adults with knee injuries had a 5.7-fold higher risk of developing knee OA in the first 11 years after injury, with the risk remaining elevated (3.4-fold) even 8-19 years later. Cruciate ligament injuries carried the highest risk (19.6% increased chance of OA after 19 years), followed by meniscal tears (10.5% increase) and knee fractures (6.6% increase), suggesting distinct injury phenotypes with varying long-term consequences.

These findings highlight the importance of injury-specific rehabilitation approaches in physiotherapy, with cruciate ligament and meniscal injuries requiring particularly intensive long-term management strategies to potentially delay or prevent OA development in young patients.

GENETIC DISSECTION OF CANINE HIP DYSPLASIA PHENOTYPES AND OSTEOARTHRITIS REVEALS THREE NOVEL LOCI.

This study aimed to identify genetic factors underlying different aspects of hip dysplasia and osteoarthritis in German Shepherd dogs by examining whether these conditions have separate genetic causes. Researchers used standardized X-rays to carefully measure joint features like alignment, bone positioning, and arthritis severity, then categorized dogs into mild, moderate, and severe dysplasia groups before conducting genome-wide genetic analysis. The study discovered three distinct genetic locations linked to different aspects of hip problems: two genes associated with joint misalignment (including one involved in bone development and another affecting cartilage-breaking enzymes), and a separate genetic region linked specifically to osteoarthritis development. These findings suggest that hip dysplasia involves multiple distinct genetic pathways rather than a single cause, which could lead to more targeted breeding strategies in dogs and potentially inform understanding of hip problems in humans, though the direct clinical applications for physiotherapy management require further research.

CLASSIC CHINESE ACUPUNCTURE VERSUS DIFFERENT TYPES OF CONTROL GROUPS FOR THE TREATMENT OF CHRONIC PAIN: REVIEW OF RANDOMIZED CONTROLLED TRIALS (2000-2018).

This systematic review aimed to evaluate the effectiveness of classic Chinese acupuncture for chronic pain treatment by comparing it against different types of control groups in randomized controlled trials published between 2000-2018. The researchers analyzed 61 studies from major databases, assessing pain outcomes using standardized measures like VAS and WOMAC scales, and evaluated study quality using established criteria (CBNG and STRICTA checklists).

The findings showed good evidence that acupuncture is more effective than no treatment or waiting lists, and reasonable evidence that it outperforms conventional care, though evidence was limited when compared to placebo treatments involving needle expectations. The study did not specifically identify distinct chronic pain phenotypes or subgroups that respond differently to acupuncture treatment.

For physiotherapy and pain management practice, these results suggest acupuncture may be a valuable adjunctive treatment option for chronic pain patients, particularly when integrated with conventional care, though more high-quality research is needed to establish clearer evidence for its effectiveness compared to placebo interventions.

RECENT ADVANCES IN UNDERSTANDING THE PHENOTYPES OF OSTEOARTHRITIS.

This narrative review aimed to examine recent advances in understanding the different types (phenotypes) of osteoarthritis and how they might be used to improve treatment approaches. The authors reviewed current research on both the clinical presentations and underlying molecular mechanisms that drive different forms of osteoarthritis. The key finding is that osteoarthritis represents multiple distinct disease subtypes with different underlying causes, progression rates, and molecular pathways, rather than a single uniform condition - with most patients having slowly progressing disease while a minority experience rapid progression. These insights suggest that identifying patients with rapidly progressing osteoarthritis using imaging and blood-based biomarkers could enable more targeted, personalized treatments and improve the effectiveness of clinical trials testing new therapies.

ΑKLOTHO AND STGFΒR2 TREATMENT COUNTERACT THE OSTEOARTHRITIC PHENOTYPE DEVELOPED IN A RAT MODEL.

I apologize, but I cannot provide a meaningful summary of this research paper because the abstract is not available (marked as "NA").

To write an accurate summary focusing on the study objective, methods, phenotype findings, and physiotherapy implications, I would need access to the full abstract or paper content. The title suggests this is an animal study investigating how αKlotho and sTGFβR2 treatments might reverse osteoarthritic changes in rats, but without the abstract details, I cannot reliably describe the specific methods used, phenotyping results, or clinical implications.

If you can provide the abstract text, I'd be happy to create the concise 3-4 sentence summary you requested.

SPECTRUM OF MUSCULOSKELETAL DISORDERS IN NIGERIANS WITH TYPES 2 DIABETES MELLITUS: PREVALENCE AND PREDICTORS.

**Summary:**

This study aimed to determine how common musculoskeletal problems are in Nigerian adults with type 2 diabetes and identify what factors predict these conditions. Researchers compared 268 people with diabetes to 268 people without diabetes using questionnaires and standardized diagnostic criteria. People with diabetes had much higher rates of musculoskeletal disorders overall (56% vs 22%), with significantly more osteoarthritis, back problems, joint stiffness, frozen shoulder, and rotator cuff issues, while older age and larger waist circumference were the strongest predictors of these problems. These findings suggest that physiotherapists and healthcare providers should routinely screen diabetic patients for musculoskeletal complications and consider targeting interventions toward older patients and those with central obesity to prevent or manage these conditions.

THE SYNOVIAL FLUID FROM PATIENTS WITH FOCAL CARTILAGE DEFECTS CONTAINS MESENCHYMAL STEM/STROMAL CELLS AND MACROPHAGES WITH PRO- AND ANTI-INFLAMMATORY PHENOTYPES.

This study aimed to characterize the types of cells found in synovial fluid from patients with focal cartilage defects to better understand early osteoarthritis processes. The researchers analyzed synovial fluid from 21 patients using cell culture techniques and flow cytometry to identify different cell types and their properties, including their ability to form cartilage and their inflammatory characteristics.

The key findings revealed that synovial fluid contains a mixed population of cells, including mesenchymal stem cells (which can potentially repair cartilage) and macrophages displaying both pro-inflammatory and anti-inflammatory phenotypes. Importantly, certain stem cell markers were actually associated with reduced cartilage-forming ability, suggesting that not all stem-like cells in the joint fluid are beneficial for repair.

These findings suggest that the joint environment in early osteoarthritis involves complex interactions between repair and inflammatory processes, which could inform physiotherapy approaches by highlighting the importance of managing inflammation while supporting the body's natural repair mechanisms through targeted exercise and treatment strategies.

CLINICAL PHENOTYPES BASED ON CLINICAL PROGNOSTIC FACTORS IN PATIENTS WITH SECONDARY HIP OSTEOARTHRITIS: PRELIMINARY FINDINGS FROM A PROSPECTIVE COHORT STUDY.

This study aimed to identify distinct clinical subgroups in patients with secondary hip osteoarthritis based on factors known to influence disease progression, including spinal alignment, spine mobility, and daily hip loading patterns. Researchers analyzed 50 patients using cluster analysis based on spinal posture, spine flexibility, hip joint loading during daily activities, and baseline joint space measurements. Three phenotypes emerged with similar progression rates: young patients with high daily hip loading (30%), older patients with reduced joint space and limited spinal mobility (42%), and patients with altered thoracic spine alignment and restricted thoracic mobility (28%). These findings suggest that physiotherapy and management strategies could be tailored to each subgroup - targeting load management for younger patients, addressing spinal mobility restrictions in older patients, and focusing on thoracic spine alignment and mobility issues in the third group.

CORRELATION NETWORK ANALYSIS SHOWS DIVERGENT EFFECTS OF A LONG-TERM, HIGH-FAT DIET AND EXERCISE ON EARLY STAGE OSTEOARTHRITIS PHENOTYPES IN MICE.

This study aimed to understand how diet-induced obesity and exercise interact to influence early-stage knee osteoarthritis development in mice, and to identify distinct pre-disease phenotypes. Researchers fed mice either control or high-fat diets for 31 weeks, with half of each group also given access to running wheels, then used advanced imaging and network analysis to examine relationships between systemic factors (metabolism, inflammation, function) and local joint changes. While neither high-fat diet nor exercise significantly changed average cartilage damage scores, the study revealed that each of the four diet-exercise combinations (control diet ± exercise, high-fat diet ± exercise) created unique patterns of connections between systemic and local factors, suggesting distinct "pre-osteoarthritis" phenotypes exist before obvious joint damage appears. These findings indicate that obesity may reduce exercise's protective effects and highlight the importance of considering individual patient phenotypes when developing personalized rehabilitation strategies, rather than using one-size-fits-all approaches for osteoarthritis prevention and management.

OSTEOARTHRITIS AND INFLAMMATION: A SERIOUS DISEASE WITH OVERLAPPING PHENOTYPIC PATTERNS.

This review aimed to examine osteoarthritis (OA) as a serious disease and explore its different phenotypic patterns to better understand treatment approaches. The authors conducted a narrative review focusing on the pathophysiology and clinical presentations of OA, identifying three key overlapping phenotypes: post-trauma, metabolic, and aging-related OA. The main finding was that patients typically experience multiple phenotypes simultaneously or sequentially during their disease progression, rather than fitting into a single category, which helps explain the varied presentations and responses to treatment seen in clinical practice. This phenotype-based understanding suggests that physiotherapy and other treatments should be tailored to individual patients based on their specific phenotypic features and disease pathways, potentially leading to more effective and personalized management strategies.

DISTINCT TRIBOLOGICAL ENDOTYPES OF PATHOLOGICAL HUMAN SYNOVIAL FLUID REVEAL CHARACTERISTIC BIOMARKERS AND VARIATION IN EFFICACY OF VISCOSUPPLEMENTATION AT REDUCING LOCAL STRAINS IN ARTICULAR CARTILAGE.

This study aimed to understand why viscosupplementation (hyaluronic acid injections) works better for some osteoarthritis patients than others by examining different types of pathological joint fluid. Researchers analyzed joint fluid samples from patients, grouped them by inflammation levels, and tested how well they lubricated cartilage before and after adding hyaluronic acid using specialized laboratory measurements.

The study identified distinct "tribological endotypes" - different subgroups of joint fluid with unique lubrication properties that could be identified by specific biomarkers including neutrophils, IL-8, and lubricin levels. Importantly, hyaluronic acid supplementation was most effective at reducing harmful cartilage strains in a subset of highly inflammatory joint fluids.

These findings suggest that osteoarthritis patients could potentially be stratified into subgroups based on their joint fluid biomarkers to predict who would benefit most from viscosupplementation, moving toward more personalized treatment approaches in physiotherapy and osteoarthritis management.

DO KNEE PAIN PHENOTYPES HAVE DIFFERENT RISKS OF TOTAL KNEE REPLACEMENT?

This study aimed to determine whether different knee pain phenotypes in osteoarthritis patients have varying risks of requiring total knee replacement (TKR) over 12 years. Researchers analyzed data from 963 participants using MRI scans, psychological assessments, and medical records, identifying three distinct pain phenotypes through statistical modeling and tracking TKR outcomes via a national registry.

The study found that patients in Class 1 (high emotional problems, low structural damage) and Class 2 (low emotional problems, high structural damage) had significantly higher TKR risks compared to Class 3 (low emotional problems, low structural damage), with hazard ratios of 4.81 and 9.23 respectively. Notably, patients with emotional problems but minimal structural damage (Class 1) still had substantially higher surgery rates than those with neither issue, suggesting psychological factors strongly influence treatment decisions.

These findings indicate that pain phenotypes can help predict which patients are most likely to need joint replacement, and highlight that emotional/psychological status may be a stronger driver for surgery than actual structural joint damage. This suggests physiotherapy and osteoarthritis management should include targeted psychological interventions alongside traditional treatments, and that surgical decision-making processes may need refinement to optimize patient selection for TKR.

A CONSENSUS-BASED FRAMEWORK FOR CONDUCTING AND REPORTING OSTEOARTHRITIS PHENOTYPE RESEARCH.

This study aimed to develop a standardized framework for researching osteoarthritis (OA) phenotypes - different subtypes of the condition that may require distinct treatment approaches. The researchers used a Delphi consensus process with 25 OA experts over four rounds to agree on key definitions and reporting standards for phenotype studies. They successfully defined OA phenotypes as subtypes that share similar underlying disease mechanisms, pain processes, and structural/functional effects, while establishing guidelines for how future phenotype research should be conducted and reported. This framework is intended to improve the consistency and quality of OA subtype research, which could ultimately lead to more personalized and effective treatments for different groups of patients, including more targeted physiotherapy and rehabilitation approaches.

EFFECTS OF CELL PHENOTYPE AND SEEDING DENSITY ON THE CHONDROGENIC CAPACITY OF HUMAN OSTEOARTHRITIC CHONDROCYTES IN TYPE I COLLAGEN SCAFFOLDS.

This study investigated whether cartilage cells (chondrocytes) from osteoarthritis patients could be used for cartilage repair treatments, testing different cell types and densities in collagen scaffolds. Researchers cultured osteoarthritic chondrocytes in laboratory conditions for 2 weeks and implanted them into mice for 4 weeks, measuring cartilage-forming genes and tissue quality using molecular and microscopic techniques. The findings showed that osteoarthritic chondrocytes with better cellular characteristics, when packed at high density in collagen scaffolds, successfully produced healthy cartilage markers and formed quality cartilage tissue. This suggests that cartilage cells from older osteoarthritis patients could potentially be used for cartilage repair procedures (like MACI), offering new treatment options for elderly patients who are typically not considered good candidates for such interventions.

IDENTIFICATION OF KNEE OSTEOARTHRITIS DISABILITY PHENOTYPES REGARDING ACTIVITY LIMITATION: A CLUSTER ANALYSIS.

This study aimed to identify distinct disability subgroups in people with knee osteoarthritis based on their activity limitations to improve treatment planning. Researchers used cluster analysis on 250 participants with knee OA, focusing on three key activities: maintaining standing position, stair climbing time, and 40-meter walking speed, then validated these groups by comparing pain, joint mobility, muscle strength, and daily participation levels.

The analysis revealed four distinct phenotypes ranging from no disability to severe disability, with each group showing significantly different levels of pain, range of motion, muscle strength, and participation in daily activities - those with greater activity limitations had worse symptoms across all measures. These findings suggest that physiotherapy and management approaches could be tailored to each phenotype's specific disability level, with more intensive interventions needed for severely disabled groups and maintenance strategies for those with minimal limitations.

DIFFERENTIAL PATTERNS OF PATHOLOGY IN AND INTERACTION BETWEEN JOINT TISSUES IN LONG-TERM OSTEOARTHRITIS WITH DIFFERENT INITIATING CAUSES: PHENOTYPE MATTERS.

This study aimed to determine whether different causes of osteoarthritis (OA) lead to distinct patterns of joint tissue damage and disease progression by comparing two mouse models over 16 weeks. Researchers used mice with either mechanical joint injury (DMM model) or immune-driven arthritis (AIA model) and analyzed how different joint tissues (cartilage, bone, synovium) were damaged and interacted with each other over time.

The study found that while both models resulted in similar overall joint damage by 16 weeks, they showed completely different patterns of how tissue damage developed and which tissues influenced each other. The mechanical injury model was characterized by strong links between cartilage breakdown and bone changes, while the immune-driven model showed stronger connections between inflammation and cartilage damage.

These findings suggest that OA patients with different underlying causes (such as previous injury versus inflammatory conditions) may represent distinct disease subtypes requiring different treatment approaches, even when their joints look similarly damaged on scans or X-rays. For physiotherapy and rehabilitation, this implies that treatment strategies should be tailored based on what initially caused a patient's OA, not just the current severity of their symptoms.

CHANGES OF SOMATOSENSORY PHENOTYPE IN THE COURSE OF DISEASE IN OSTEOARTHRITIS PATIENTS.

This study investigated how pain sensitivity patterns and function change over time in osteoarthritis patients, comparing those who received joint replacement surgery versus those who didn't. The researchers used questionnaires and detailed sensory testing on 31 patients at two time points 22-49 weeks apart, measuring pain sensitivity to different stimuli (heat, cold, mechanical pressure) in the thigh area.

The study identified two distinct response patterns: patients without surgery showed worsening pain sensitivity (especially to cold) and no improvement in pain or function, while those who had joint replacement surgery showed reduced mechanical pain sensitivity and improved function, though they developed new sensitivities to heat pain and some sensory loss. Importantly, joint replacement improved pain and physical function but did not improve quality of life in either group.

These findings suggest that osteoarthritis patients may need different physiotherapy approaches depending on their treatment path - those avoiding surgery may benefit from interventions targeting progressive sensitization, while post-surgical patients may need rehabilitation strategies that account for new sensory changes while building on their improved pain and function.

DIFFERENTIAL EXPRESSION OF CEREBROSPINAL FLUID NEUROINFLAMMATORY MEDIATORS DEPENDING ON OSTEOARTHRITIS PAIN PHENOTYPE.

This study investigated whether different pain patterns in osteoarthritis patients are associated with specific brain inflammation markers by comparing cerebrospinal fluid samples from 52 hip osteoarthritis patients requiring surgery to 30 pain-free controls. Researchers used detailed pain testing and measured 10 inflammatory substances in spinal fluid to identify pain subgroups based on how patients responded to pressure, needle insertion, and repeated stimulation. The key finding was that osteoarthritis patients with signs of central sensitization (widespread pain sensitivity indicating changes in the central nervous system) had distinctly different inflammatory profiles, particularly elevated levels of specific proteins like FLT-1 and IP-10, compared to those without these features. These results suggest that brain inflammation patterns could help identify different osteoarthritis pain subtypes, potentially leading to more targeted treatments - for example, patients with central sensitization features might benefit from therapies that address central nervous system changes rather than focusing solely on the affected joint.

PHENOTYPE CHANGES OF SUBCHONDRAL PLATE OSTEOBLASTS BASED ON A RAT MODEL OF OVARIECTOMY-INDUCED OSTEOARTHRITIS.

This study aimed to understand how bone cells (osteoblasts) beneath joint cartilage change in a rat model of postmenopausal osteoarthritis created by removing ovaries. The researchers compared ovariectomized rats to control rats over 9 weeks, using blood tests, bone imaging, and detailed analysis of bone cell behavior including their ability to multiply, mature, and form new bone tissue.

The study identified a distinct phenotype of subchondral osteoblasts in hormone-deficient osteoarthritis: these cells showed increased early activation and bone formation activity, but paradoxically had reduced ability to properly mineralize and form mature bone tissue. This abnormal bone cell behavior was associated with significant cartilage damage and changes in the underlying bone structure.

These findings suggest that postmenopausal osteoarthritis may represent a distinct subgroup with unique bone-cartilage interactions, where dysfunctional bone formation beneath joints contributes to cartilage breakdown. For physiotherapy and management, this implies that treatments targeting bone health and hormonal factors may be particularly important for postmenopausal women with osteoarthritis, potentially requiring different approaches than other osteoarthritis phenotypes.

EVALUATION OF MUSCULOSKELETAL PHENOTYPE OF THE G608G PROGERIA MOUSE MODEL WITH LONAFARNIB, PRAVASTATIN, AND ZOLEDRONIC ACID AS TREATMENT GROUPS.

This study aimed to characterize the bone and joint changes in a mouse model of Hutchinson-Gilford progeria syndrome (a rare aging disease) and test whether drug combinations could improve these changes. Researchers used advanced imaging and mechanical testing to examine bone structure, strength, and cartilage quality in mice treated with different combinations of three drugs: lonafarnib, pravastatin, and zoledronic acid. The progeria mice showed weakened bones prone to bending/breaking and cartilage deterioration similar to age-related joint diseases like osteoarthritis in elderly humans. While single-drug treatment (lonafarnib alone) was ineffective, combining it with pravastatin and zoledronic acid significantly improved both bone strength and cartilage structure, suggesting that multi-drug approaches may be more effective for managing musculoskeletal complications in progeria and potentially other age-related bone/joint conditions.

RECENT ADVANCES IN THE TREATMENT OF OSTEOARTHRITIS.

This review aimed to examine recent advances in personalized osteoarthritis (OA) treatment based on patient phenotyping, as current therapies fail to halt cartilage deterioration or prevent joint replacement. The authors analyzed different classification strategies that group OA patients into subgroups with distinct characteristics, identifying structural endotypes (cartilage and bone subtypes), inflammatory phenotypes, pain-driven phenotypes, and those related to aging/metabolic syndrome. Current clinical trials have targeted these specific phenotypes through cartilage/bone repair therapies, anti-inflammatory treatments via joint injections, and pain management by blocking nerve growth factors, though none have successfully modified disease progression. This phenotype-based approach suggests that physiotherapy and rehabilitation strategies should also be tailored to predominant patient characteristics - for example, anti-inflammatory exercises for inflammatory phenotypes or specific pain management techniques for pain-driven cases - rather than using one-size-fits-all treatment approaches.

THE POWER OF PROTEOMICS TO MONITOR SENESCENCE-ASSOCIATED SECRETORY PHENOTYPES AND BEYOND: TOWARD CLINICAL APPLICATIONS.

This review examined how protein analysis (proteomics) can be used to study cellular senescence and the harmful proteins that aging cells release, which contribute to diseases including osteoarthritis. The authors analyzed research from 2008-2020 focusing on how proteomics helps identify senescence biomarkers and potential drug targets for therapies that either eliminate aging cells (senolytics) or reduce their harmful secretions (senomorphics). Key findings highlighted that senescent cells and their secretory patterns are highly variable between individuals, and that protein-based approaches can detect different senescence subtypes and monitor cellular aging processes. For osteoarthritis management, this suggests that proteomic profiling could help identify patient subgroups based on their cellular aging patterns, potentially leading to personalized treatments targeting senescent cells in joints and more precise monitoring of anti-aging therapeutic interventions.

OVEREXPRESSION OF MIG-6 IN THE CARTILAGE INDUCES AN OSTEOARTHRITIS-LIKE PHENOTYPE IN MICE.

This study investigated how overexpression of MIG-6 (a protein that regulates cell growth signals) specifically in cartilage affects joint health in mice. Researchers used genetically modified mice and analyzed their knee joints at different ages using microscopy, imaging, and tissue scoring methods to assess cartilage health and bone structure. The key finding was that male mice with excess MIG-6 in their cartilage developed accelerated cartilage breakdown resembling osteoarthritis by 12-18 months of age, with reduced protective factors and increased cartilage-degrading enzymes. These results suggest that the MIG-6/EGFR signaling pathway is crucial for maintaining healthy joints and could represent a new target for developing osteoarthritis treatments, potentially leading to therapies that modulate this pathway to prevent or slow cartilage degeneration.

ASSOCIATION OF KNEE OA STRUCTURAL PHENOTYPES TO RISK FOR PROGRESSION: A SECONDARY ANALYSIS FROM THE FOUNDATION FOR NATIONAL INSTITUTES OF HEALTH OSTEOARTHRITIS BIOMARKERS STUDY (FNIH).

This study aimed to identify distinct knee osteoarthritis structural patterns (phenotypes) using MRI scans and determine which patterns predict worsening of the condition over 4 years. Researchers analyzed MRI scans from 485 knees using detailed scoring systems and grouped patients into three main phenotypes: subchondral bone, cartilage/meniscus, and inflammatory patterns, then tracked progression of joint damage and pain.

The study found that 75% of patients didn't fit into any specific phenotype, while 20% had the bone phenotype, 5% had the cartilage/meniscus phenotype, and 4% had the inflammatory phenotype. Importantly, only patients with the bone phenotype had significantly higher risk (about 65-81% increased odds) of experiencing both structural joint damage and worsening pain over the study period.

These findings suggest that identifying patients with bone-related structural changes on MRI could help physiotherapists and clinicians predict which individuals are most likely to experience rapid osteoarthritis progression, potentially allowing for earlier or more intensive interventions to slow disease advancement.

AN IN-DEPTH STUDY OF THE ASSOCIATIONS BETWEEN OSTEOARTHRITIS- AND OSTEOPOROSIS-RELATED PHENOTYPES AT DIFFERENT SKELETAL LOCATIONS.

This study aimed to clarify the controversial relationship between osteoarthritis (OA) and bone mineral density (BMD) at different body locations by examining two ethnic populations (Chuvashian and British, totaling 3,784 individuals). Researchers used X-rays to assess OA severity in hands, knees, and spine, and measured bone density at multiple sites using dual X-ray absorptiometry.

The study identified distinct OA phenotypes with opposite bone density patterns: hand OA was associated with lower bone density in the hands and arms plus increased wrist fracture risk, while knee and spine OA were linked to higher bone density in the spine, hips, and throughout the body. These findings suggest that hand OA behaves differently from knee and spine OA in terms of bone health.

For physiotherapy and clinical management, this means that people with hand OA may need additional bone health monitoring and fall prevention strategies due to their fracture risk, while those with knee or spine OA may have different bone-related considerations in their treatment plans.

INFLAMMATORY AND NONINFLAMMATORY SYNOVIAL FLUIDS EXHIBIT NEW AND DISTINCT TRIBOLOGICAL ENDOTYPES.

This study aimed to investigate how hyaluronic acid (HA) injections affect joint lubrication in different types of arthritis patients. Researchers analyzed synovial fluid samples from patients with non-inflammatory osteoarthritis and inflammatory arthritis, measuring lubricating properties and chemical composition before and after adding HA treatment. The study identified distinct lubrication patterns or "endotypes" - while most patients showed normal lubrication that improved with HA treatment, a subset of inflammatory arthritis patients had erratic, poor lubrication associated with low lubricin levels that did not respond well to HA. These findings suggest that HA injections may be less effective for certain arthritis patients, particularly those with inflammatory disease and poor baseline lubrication, indicating a need for personalized treatment approaches and potentially different therapeutic strategies for different patient subgroups.

ANALYSIS OF GENETICALLY INDEPENDENT PHENOTYPES IDENTIFIES SHARED GENETIC FACTORS ASSOCIATED WITH CHRONIC MUSCULOSKELETAL PAIN CONDITIONS.

This study aimed to identify shared genetic factors underlying chronic musculoskeletal pain at different body locations (back, neck/shoulder, hip, and knee) by reducing the complexity of pain phenotypes. The researchers used principal component analysis on genetic data to create four genetically independent phenotypes (GIPs), with the primary component (GIP1) accounting for nearly 80% of genetic variance across all pain conditions. They discovered six genetic locations associated with these phenotypes, with GIP1 showing strong links to nervous system function, body composition, psychological traits, and osteoarthritis, suggesting it represents a "biopsychological" pain component related to how people perceive and process pain. These findings support the concept that chronic musculoskeletal pain conditions share common underlying mechanisms, which could help physiotherapists develop more targeted, personalized treatment approaches that address both the physical and psychological aspects of pain management.

NAVITOCLAX (ABT263) REDUCES INFLAMMATION AND PROMOTES CHONDROGENIC PHENOTYPE BY CLEARING SENESCENT OSTEOARTHRITIC CHONDROCYTES IN OSTEOARTHRITIS.

This study investigated whether a drug called Navitoclax (ABT263) could help treat osteoarthritis by removing damaged, aged cells (senescent cells) that accumulate in joints and cause inflammation. The researchers tested the drug on osteoarthritic cartilage cells in laboratory cultures and in rats with surgically-induced osteoarthritis, using direct joint injections. They found that ABT263 successfully eliminated the problematic senescent cells, reduced inflammatory chemicals, improved cartilage cell function, and protected against cartilage and bone damage in the rat model. These findings suggest that targeting senescent cells with drugs like ABT263 could offer a new treatment approach for osteoarthritis, potentially providing physiotherapists and clinicians with a therapeutic option that addresses the underlying inflammatory processes rather than just managing symptoms.

COMPARISON OF CANINE STIFLE KINEMATIC ANALYSIS AFTER TWO TYPES OF TOTAL KNEE ARTHROPLASTY: A CADAVERIC STUDY.

This cadaveric study aimed to compare the biomechanical performance of two different total knee replacement designs in dogs with severe osteoarthritis following cruciate ligament rupture. Researchers tested four conditions (intact knees, ruptured ligaments, and two implant designs with and without a tibial peg) using biomechanical testing machines and measured various joint movements including rotation, translation, and range of motion. The study found that the implant design with a tibial peg (TKAP) restored more normal knee mechanics compared to the design without a peg (TKAN), which showed excessive unwanted movements in multiple directions. These findings suggest that implant design features like tibial pegs are important for achieving better functional outcomes in total knee replacement, which could inform both veterinary and potentially human orthopedic surgery approaches for managing end-stage osteoarthritis.

IDENTIFICATION OF TGFΒ SIGNATURES IN SIX MURINE MODELS MIMICKING DIFFERENT OSTEOARTHRITIS CLINICAL PHENOTYPES.

This study aimed to identify different molecular signatures of TGFβ (a protein involved in cartilage health) across six mouse models that represent different types of osteoarthritis seen in humans. The researchers used standardized laboratory procedures across seven expert labs and analyzed gene expression in various OA models including post-traumatic, aging-related, and inflammatory types, comparing them to appropriate controls.

The key finding was that each OA model showed a unique molecular signature with no single gene being affected in all six models, highlighting the diversity of OA types. Importantly, they identified a three-gene signature (GDF5-CD36-LTBP4) that could distinguish between different OA subgroups: models with mechanical damage showed increased CD36, while those with both mechanical and inflammatory components showed increased GDF5 and LTBP4.

These findings suggest that different types of osteoarthritis have distinct underlying molecular mechanisms, which could lead to more personalized physiotherapy and treatment approaches tailored to specific OA phenotypes rather than using a one-size-fits-all management strategy.

DISTAL FEMORAL PHENOTYPES IN ASIAN VARUS OSTEOARTHRITIC KNEES.

This study aimed to examine the bone shape patterns (phenotypes) of the thigh bone (distal femur) in Asian patients with varus osteoarthritic knees, where the knee angles inward. The researchers analyzed X-rays from 128 patients undergoing knee replacement surgery, measuring various bone angles and comparing patients with severe varus alignment (≥10°) to those with milder varus alignment (<10°).

The key finding was that one-third of patients with varus osteoarthritic knees actually had a valgus (outward-angled) thigh bone shape, while the inward knee alignment was primarily caused by changes in the shin bone (tibia) rather than the thigh bone. The study revealed that more severe varus alignment was associated with greater changes in the shin bone angle and more joint space narrowing.

These findings suggest that osteoarthritic knee deformities are more complex than previously thought, with different bone shape patterns contributing to the overall alignment, which could inform more personalized surgical planning and potentially guide targeted physiotherapy approaches for different patient subgroups.

REDOX AND MTOR-DEPENDENT REGULATION OF PLASMA LAMELLAR CALCIUM INFLUX CONTROLS THE SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE.

This study aimed to understand how cellular aging processes (specifically the senescence-associated secretory phenotype or SASP) are controlled at the molecular level, which is relevant to osteoarthritis development. The researchers used laboratory techniques to examine how calcium movement into cells and specific cellular pathways (redox and mTOR signaling) regulate the inflammatory secretions that aging cells produce. They discovered that controlling calcium entry into cells through strategies like antioxidant treatments, channel modulation, or mTOR inhibition could block the harmful inflammatory secretions associated with cellular aging. These findings suggest that targeting calcium regulation and cellular signaling pathways could potentially slow osteoarthritis progression and other age-related joint degeneration, opening new avenues for therapeutic interventions in musculoskeletal rehabilitation.

COHORT PROFILE: THE APPLIED PUBLIC-PRIVATE RESEARCH ENABLING OSTEOARTHRITIS CLINICAL HEADWAY (IMI-APPROACH) STUDY: A 2-YEAR, EUROPEAN, COHORT STUDY TO DESCRIBE, VALIDATE AND PREDICT PHENOTYPES OF OSTEOARTHRITIS USING CLINICAL, IMAGING AND BIOCHEMICAL MARKERS.

**Study Summary:**

The APPROACH study aims to identify and validate different types (phenotypes) of knee osteoarthritis patients who are most likely to experience disease progression, using a combination of clinical assessments, imaging, and blood/urine markers. Researchers used machine learning to pre-select 297 patients from existing studies who were predicted to have worsening joint damage or knee pain, then followed them for 2 years with comprehensive testing including MRI scans, X-rays, movement analysis, and performance tests. The selected patients showed more severe disease at baseline compared to those not selected, with worse joint space narrowing and significantly higher pain scores, confirming the selection process worked as intended. This research could lead to better-targeted treatments for osteoarthritis by identifying which patients are most likely to worsen and may respond differently to specific therapies, potentially helping physiotherapists and clinicians tailor rehabilitation approaches based on individual patient phenotypes.

MECHANOTRANSDUCTION AND STIFFNESS-SENSING: MECHANISMS AND OPPORTUNITIES TO CONTROL MULTIPLE MOLECULAR ASPECTS OF CELL PHENOTYPE AS A DESIGN CORNERSTONE OF CELL-INSTRUCTIVE BIOMATERIALS FOR ARTICULAR CARTILAGE REPAIR.

This review study aimed to examine how material stiffness affects cell behavior and could be used to improve biomaterials for cartilage repair. The researchers analyzed existing research on how cells sense and respond to different material stiffness levels, focusing on cartilage cells (chondrocytes) and stem cells (mesenchymal stromal cells).

The key finding was that material stiffness significantly influences multiple aspects of cell behavior - including cell shape, gene expression, growth, and the ability of cells to maintain their cartilage-producing characteristics. Importantly, current clinical biomaterials for cartilage repair lack proper stiffness information and don't control cell behavior equally well, particularly in damaged/degenerative tissue conditions.

The implications for treatment suggest that carefully controlling the stiffness of biomaterials used in cartilage repair procedures could dramatically improve outcomes by better guiding cells to produce high-quality repair tissue, representing a promising new approach for designing more effective cartilage treatments.

RELATIONSHIP BETWEEN SYNOPTIC WEATHER TYPE AND EMERGENCY DEPARTMENT VISITS FOR DIFFERENT TYPES OF PAIN ACROSS THE TRIANGLE REGION OF NORTH CAROLINA.

This study examined how different weather patterns affect emergency department visits for various pain conditions including osteoarthritis, rheumatoid arthritis, fibromyalgia, and back pain in North Carolina over seven years. Researchers analyzed the relationship between specific weather types (air masses) and ED visits for pain-related conditions using statistical methods with confidence intervals. The key finding was that moist tropical weather conditions were associated with the highest number of emergency visits for all pain conditions studied, while moist polar weather types resulted in the fewest visits; surprisingly, barometric pressure changes during weather transitions showed no significant relationship with pain episodes. These results suggest that certain weather patterns may serve as environmental triggers for pain flares in people with musculoskeletal conditions, potentially helping physiotherapists and patients anticipate and prepare for symptom worsening during specific weather conditions.

EFFECTS OF THE WISH-TYPE S-FORM HIP BRACE ON MUSCLE STRENGTH IN PATIENTS WITH OSTEOARTHRITIS OF THE HIP: A SHORT-TERM LONGITUDINAL STUDY.

This study examined how wearing the WISH-type S-form hip brace affects muscle strength changes over time in people with hip osteoarthritis. Researchers measured hip and knee muscle strength using a handheld dynamometer in 42 patients over 6 months of brace use during daily walking.

The study found that patients initially had weaker hip flexion, hip abduction, and knee extension muscles on their arthritic side compared to their healthy side, while hip adduction weakness affected both sides equally. After 6 months of using the brace during daily walking, hip abduction strength in the affected leg improved to match the strength of the unaffected leg, while hip adduction and knee extension showed beneficial changes over time.

These findings suggest that the WISH brace may help restore muscle balance around the hip joint, particularly by strengthening the important hip abductor muscles that help stabilize walking. For physiotherapy practice, this indicates that incorporating supportive bracing during walking exercises could be an effective strategy for addressing muscle weakness patterns commonly seen in hip osteoarthritis patients.

DIFFERENT TYPES OF CARTILAGE NEOTISSUE FABRICATED FROM COLLAGEN HYDROGELS AND MESENCHYMAL STROMAL CELLS VIA SOX9, TGFB1 OR BMP2 GENE TRANSFER.

This study aimed to create different types of artificial cartilage tissue that could mimic the various zones found in natural cartilage, using stem cells from osteoarthritis patients. The researchers genetically modified mesenchymal stromal cells (stem cells from bone marrow) to produce three different growth factors (SOX9, TGFB1, or BMP2) and grew them in collagen gels for three weeks to see what type of cartilage would develop.

All three growth factors successfully converted the stem cells into cartilage-producing cells, but each created cartilage with different characteristics - specifically, different levels of "hypertrophy" (a mature cartilage state), with BMP2 producing the most mature cartilage, followed by TGFB1, then SOX9. This technology could potentially be used to regenerate specific damaged areas of cartilage by matching the appropriate type of engineered cartilage to the particular zone that needs repair, offering a more targeted approach to cartilage regeneration therapy for osteoarthritis patients.

METABOLOMIC ANALYSIS COUPLED WITH EXTREME PHENOTYPE SAMPLING IDENTIFIED THAT LYSOPHOSPHATIDYLCHOLINES ARE ASSOCIATED WITH MULTISITE MUSCULOSKELETAL PAIN.

This study aimed to identify blood-based metabolic markers that could distinguish people with widespread musculoskeletal pain from those with minimal pain. Researchers analyzed blood samples from 205 participants from an osteoarthritis study, comparing 83 people with pain at 7 or more body sites against 122 people with pain at 1 or fewer sites, using advanced metabolic profiling techniques. The study found that two specific molecules called lysophosphatidylcholines were significantly elevated in people with multisite pain, and that this pain pattern was more common in women and younger individuals, often accompanied by poorer function and higher cholesterol levels. These metabolic markers could potentially help clinicians identify patients who may benefit from comprehensive, whole-body pain management approaches rather than single-site treatments, suggesting that multisite musculoskeletal pain represents a distinct condition requiring specialized physiotherapy and rehabilitation strategies.

SETTING UP DISTINCTIVE OUTCOME MEASURES FOR EACH OSTEOARTHRITIS PHENOTYPE.

This study aimed to propose a framework for using specific outcome measures tailored to different osteoarthritis (OA) phenotypes rather than applying generic measures to all patients. The authors developed a conceptual approach suggesting that each OA phenotype should be assessed using outcome measures that match the underlying biological mechanisms driving that particular type of arthritis. The key finding emphasized that OA patients fall into distinct subgroups (phenotypes) based on different disease processes, and these subgroups may respond differently to treatments and show varying patterns of symptoms and progression. This phenotype-specific approach could improve clinical trials and lead to more personalized treatments, suggesting that physiotherapists and clinicians should consider tailoring their assessment tools and treatment strategies based on the specific type of OA each patient presents with.

HYPEROSMOLAR IONIC SOLUTIONS MODULATE INFLAMMATORY PHENOTYPE AND SGAG LOSS IN A CARTILAGE EXPLANT MODEL.

This laboratory study aimed to test whether different salt solutions could reduce cartilage breakdown and inflammation in a model of osteoarthritis using cow cartilage samples. Researchers exposed cartilage pieces to an inflammatory substance (TNF-α) to mimic osteoarthritis damage, then treated them with high-concentration solutions of lithium chloride, potassium chloride, or sodium chloride for 6 days. The study revealed distinct cartilage responses to different salts: lithium chloride reduced both cartilage breakdown and harmful enzyme production (similar to the steroid dexamethasone), while potassium chloride actually worsened cartilage damage, and sodium chloride had no effect. These findings suggest that specific salt solutions, particularly lithium-based ones, might be developed as new injectable treatments for osteoarthritis, though human studies would be needed to confirm safety and effectiveness.

REFINING SURGICAL MODELS OF OSTEOARTHRITIS IN MICE AND RATS ALTERS PAIN PHENOTYPE BUT NOT JOINT PATHOLOGY.

This study aimed to develop more realistic animal models of osteoarthritis by refining surgical techniques in mice and rats to better understand the relationship between joint damage and pain. Researchers compared traditional versus modified surgical approaches, measuring pain behaviors (weight-bearing changes and sensitivity) and examining joint tissue damage over 16 weeks post-surgery.

The key finding was that different surgical approaches produced distinct pain phenotypes - modified techniques resulted in less pain behavior despite causing similar joint damage, while in rats, inflammation (synovitis) appeared before pain, followed later by cartilage damage. This mirrors the complexity seen in human osteoarthritis, where joint damage doesn't always correlate directly with pain levels.

These refined animal models could help researchers better understand why some people with osteoarthritis experience significant pain while others with similar joint damage do not, potentially leading to more targeted physiotherapy and pain management approaches that address the underlying mechanisms rather than just structural changes.

ROLE OF GLUCOSE METABOLISM IN AGGRESSIVE PHENOTYPE OF FIBROBLAST-LIKE SYNOVIOCYTES: LATEST EVIDENCE AND THERAPEUTIC APPROACHES IN RHEUMATOID ARTHRITIS.

This review examined how glucose metabolism contributes to aggressive behavior in fibroblast-like synoviocytes (FLS cells) in rheumatoid arthritis (RA) joints. The authors analyzed current evidence on metabolic changes in FLS cells, focusing on key glycolytic enzymes like hexokinase 2 (HK2) that are elevated in RA compared to osteoarthritis. They found that aggressive FLS phenotypes show increased glucose metabolism, and that blocking these metabolic pathways can reduce joint damage in arthritis models. The findings suggest that targeting specific enzymes like HK2 could offer safer, more selective treatments for RA than broadly inhibiting glucose metabolism, potentially leading to new therapeutic approaches that specifically target the aggressive cellular behavior driving joint destruction.

WHAT GENERAL AND PAIN-ASSOCIATED PSYCHOLOGICAL DISTRESS PHENOTYPES EXIST AMONG PATIENTS WITH HIP AND KNEE OSTEOARTHRITIS?

This study aimed to identify different psychological distress patterns (phenotypes) among people with hip and knee osteoarthritis to better tailor their treatment. Researchers compared psychological distress levels between 1,239 osteoarthritis patients and 871 people with other musculoskeletal conditions using a comprehensive psychological assessment tool, then used statistical modeling to identify distinct subgroups. They found that osteoarthritis patients generally had higher levels of psychological distress and identified four distinct phenotypes: high distress (52% of patients), low distress (26%), low self-efficacy and acceptance (15%), and negative pain coping (7%). These findings suggest that current osteoarthritis care focusing mainly on medical treatments may be insufficient, and that physiotherapy and rehabilitation should be tailored to address specific psychological needs - such as providing pain coping skills training and psychological support for the majority of patients who fall into the high distress category.

UNDERSTANDING THE PHENOTYPICAL REPRESENTATIONS OF TEMPOROMANDIBULAR OSTEOARTHRITIS FOR EFFECTIVE MANAGEMENT.

I apologize, but I cannot provide a meaningful summary of this research as the abstract is listed as "NA" (not available).

To write an accurate summary focusing on the study objective, methods, phenotype findings, and clinical implications you've requested, I would need access to the actual abstract content that describes:
- The study's aims and design
- The methodology used for phenotyping
- The specific temporomandibular osteoarthritis subgroups identified
- The clinical or management recommendations

If you could provide the complete abstract, I would be happy to create a concise 3-4 sentence summary in plain language focusing on the phenotyping aspects and rehabilitation implications you've outlined.

NA

This study aimed to identify genetic factors associated with hand osteoarthritis by creating more specific disease subgroups based on which joints are affected together. Researchers analyzed genetic data from nearly 10,000 people in the Rotterdam Study, grouping participants into three hand OA patterns based on X-ray severity across different hand joints, then verified their findings in an independent group of over 1,200 people. The team discovered two new genetic locations specifically linked to thumb joint arthritis and identified several genetic variants that increase arthritis risk across multiple joints (hands, hips, and knees), suggesting some common underlying disease mechanisms. These findings support the value of studying more specific arthritis subgroups rather than treating all hand OA as one condition, which could eventually lead to more personalized prevention strategies and treatments tailored to individual genetic risk profiles and joint involvement patterns.

INCIDENCE OF AND RISK FACTORS FOR DEEP VEIN THROMBOSIS IN PATIENTS UNDERGOING OSTEOTOMIES AROUND THE KNEE: COMPARATIVE ANALYSIS OF DIFFERENT OSTEOTOMY TYPES.

This study aimed to compare deep vein thrombosis (DVT) rates and identify risk factors across different types of knee osteotomy surgeries performed for knee osteoarthritis with varus (inward) alignment. Researchers used ultrasound scans to detect blood clots in 326 knees from 267 patients before and one week after three different osteotomy procedures: medial opening wedge, lateral closed wedge, and double level osteotomies.

The study found that DVT occurred in 13.8% of patients overall, with significantly higher rates after lateral closed wedge osteotomy (22.6%) compared to medial opening wedge (11.9%) and double level procedures (6.8%). Most blood clots formed below the knee level and no patients developed serious lung complications.

These findings suggest that patients undergoing lateral closed wedge osteotomy represent a higher-risk subgroup requiring enhanced monitoring and potentially more intensive blood clot prevention strategies, which should inform surgical decision-making and post-operative physiotherapy planning for knee osteoarthritis patients.

MOHAWK IS A TRANSCRIPTION FACTOR THAT PROMOTES MENISCUS CELL PHENOTYPE AND TISSUE REPAIR AND REDUCES OSTEOARTHRITIS SEVERITY.

This study aimed to investigate MOHAWK (MKX) as a key transcription factor that controls meniscus cell characteristics and could be used for tissue repair strategies. The researchers used RNA sequencing data from human tissues, cell culture experiments with mesenchymal stem cells, tissue engineering approaches with decellularized meniscus scaffolds, and mouse models of osteoarthritis to test MKX's effects.

The key findings showed that MKX is highly concentrated in meniscus tissue compared to other body tissues and acts as a master regulator that controls genes responsible for maintaining healthy meniscus cells. When MKX was combined with a growth factor (TGF-β3) and applied to stem cells on special scaffolds, it successfully transformed these cells into meniscus-like cells and improved tissue repair, while injection of MKX into arthritic mouse joints reduced cartilage and meniscus damage.

These findings suggest that different phenotypes or subgroups of meniscus cells may be defined by their MKX expression levels, with higher MKX promoting healthier, more repair-capable cells. For physiotherapy and clinical management, this research points toward future regenerative therapies that could enhance meniscus healing and potentially prevent osteoarthritis progression following meniscus injuries, though such treatments would need further development before clinical application.

ENDOTYPES OF PRIMARY OSTEOARTHRITIS IDENTIFIED BY PLASMA METABOLOMICS ANALYSIS.

This study aimed to identify distinct subtypes (endotypes) of osteoarthritis using blood metabolite analysis to better understand the biological differences between OA patients. Researchers analyzed fasting blood samples from 615 hip/knee OA patients and 237 controls, measuring 162 different metabolites and using statistical clustering methods to group patients based on their metabolic profiles.

The analysis revealed three distinct OA endotypes: Cluster A (66 patients) characterized by elevated butyrylcarnitine suggesting muscle weakness and higher rates of obesity and diabetes; Cluster B (200 patients) with low arginine levels and increased heart disease; and Cluster C (349 patients) with low inflammatory markers and higher osteoporosis rates. Each cluster had unique metabolic signatures that corresponded to different clinical characteristics and health conditions.

These findings suggest that OA patients could benefit from personalized treatment approaches, with Cluster A patients potentially needing muscle strengthening interventions and metabolic management, Cluster B patients requiring arginine supplementation or cardiovascular considerations, and Cluster C patients needing bone health monitoring alongside standard OA physiotherapy.

NON-CANONICAL WNT5A SIGNALING THROUGH RYK CONTRIBUTES TO AGGRESSIVE PHENOTYPE OF THE RHEUMATOID FIBROBLAST-LIKE SYNOVIOCYTES.

This study aimed to investigate whether WNT5A signaling contributes to the aggressive, invasive behavior of fibroblast-like synoviocytes (joint lining cells) in rheumatoid arthritis (RA). The researchers used laboratory experiments to test cell migration and invasion after either adding WNT5A protein or blocking its expression, and examined the molecular pathways involved using gene silencing and protein analysis techniques.

The key finding was that WNT5A specifically promoted migration and invasion in RA cells but not in osteoarthritis cells, suggesting distinct disease phenotypes. WNT5A also increased production of inflammatory molecules and tissue-degrading enzymes, working through a specific receptor (RYK) and downstream signaling pathways.

These results suggest that RA synovial cells have a unique aggressive phenotype driven by WNT5A signaling, which could represent a therapeutic target for preventing joint destruction and inflammation in RA patients.

EFFECTS OF TYPES AND DEGREES OF ANKYLOSING SPONDYLITIS HIP STRUCTURAL DAMAGES ON POST-TOTAL HIP ARTHROPLASTY OUTCOME MEASUREMENTS.

This study aimed to determine how different types and severities of hip joint damage in ankylosing spondylitis (AS) patients affect recovery outcomes after total hip replacement surgery. Researchers reviewed medical records of 122 AS patients (181 hip replacements) over an average 44-month follow-up period, analyzing pre-surgery X-rays to classify hip damage patterns and comparing these to post-surgery recovery measures including walking independence, patient satisfaction, and joint mobility.

The study identified distinct damage phenotypes that significantly influenced recovery: patients with severe erosion (wearing away) of the femoral head bone took over 7 weeks to walk independently without crutches—more than 4 weeks longer than those with less severe erosion. Interestingly, patients with more acetabular sclerosis (bone hardening in the hip socket) actually had better satisfaction outcomes, while pre-surgery joint stiffness was the strongest predictor of post-surgery mobility improvements.

These findings suggest that physiotherapists and surgeons should tailor rehabilitation expectations and programs based on specific pre-surgery damage patterns, with patients showing severe bone erosion likely requiring extended support for walking recovery, while those with significant pre-operative stiffness may have the greatest potential for mobility gains.

MICRORNA-1 MODULATES CHONDROCYTE PHENOTYPE BY REGULATING FZD7 OF WNT/ Β-CATENIN SIGNALING PATHWAY.

This study aimed to investigate whether microRNA-1 (miR-1) influences osteoarthritis development by affecting cartilage cell behavior through specific molecular pathways. Researchers compared gene expression between healthy and osteoarthritic cartilage cells, then experimentally increased or decreased miR-1 levels in laboratory-grown cells to observe the effects on cartilage breakdown markers. They found that miR-1 acts as a protective factor - higher levels reduced the expression of enzymes that destroy cartilage, while lower levels increased cartilage damage, with these effects occurring through miR-1's regulation of the WNT/β-catenin signaling pathway via targeting FZD7. These findings suggest that patients with different miR-1 expression levels may represent distinct osteoarthritis subtypes, and that targeting this pathway could potentially lead to new therapeutic approaches to slow cartilage destruction, though translation to physiotherapy applications would require further research into how exercise or other interventions might influence these molecular mechanisms.

TRANSCRIPTIONAL RESPONSE OF HUMAN ARTICULAR CHONDROCYTES TREATED WITH FIBRONECTIN FRAGMENTS: AN IN VITRO MODEL OF THE OSTEOARTHRITIS PHENOTYPE.

This study aimed to validate whether treating normal cartilage cells with fibronectin fragments (pieces of protein released during cartilage breakdown) could accurately model osteoarthritis in laboratory conditions. Researchers exposed human cartilage cells to fibronectin fragments for different time periods (3, 6, or 18 hours) and analyzed changes in gene activity using advanced sequencing techniques, then compared these patterns to known osteoarthritis gene signatures.

The treatment successfully reproduced key features of osteoarthritis at the cellular level, with early inflammatory responses followed by later cell death pathways, and the overall gene expression patterns closely matched those seen in actual osteoarthritis cartilage. This validated laboratory model could help researchers better understand different osteoarthritis subtypes and test potential treatments, particularly those targeting the inflammatory processes that drive cartilage breakdown, which may inform the development of more personalized physiotherapy and rehabilitation approaches for different osteoarthritis phenotypes.

BONE PHENOTYPES IN RHEUMATOLOGY - THERE IS MORE TO BONE THAN JUST BONE.

This review aimed to examine how different rheumatological diseases (osteoarthritis, rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis) create distinct bone turnover patterns or "phenotypes" despite all affecting bone metabolism. The authors analyzed the molecular and cellular mechanisms underlying bone changes in these conditions, focusing on how different cell types (osteoblasts, osteoclasts, osteocytes, and chondrocytes) contribute to varying manifestations ranging from bone thickening (sclerosis) to bone erosion. The key finding is that these diseases produce highly diverse bone phenotypes - some areas show excessive bone formation while others show bone destruction - even within the same condition, suggesting that bone changes are more complex than simple increases or decreases in bone turnover. This understanding could help physiotherapists and clinicians develop more targeted treatments by recognizing that different patients may have distinct bone phenotypes requiring personalized management approaches, potentially guided by specific biomarkers that identify individual bone turnover patterns.

PROSTANOID RECEPTOR SUBTYPES AND ITS ENDOGENOUS LIGANDS WITH PROCESSING ENZYMES WITHIN VARIOUS TYPES OF INFLAMMATORY JOINT DISEASES.

This study aimed to compare inflammatory patterns in joint diseases by examining prostaglandin E2 (PGE2) pathways and receptor subtypes in synovial tissue from patients with joint trauma, osteoarthritis, and rheumatoid arthritis. Researchers used advanced molecular techniques (quantitative PCR and immunofluorescence microscopy) to measure inflammatory molecules and identify which specific immune cells were involved in each condition. The findings revealed distinct inflammatory "fingerprints" for each joint condition: rheumatoid arthritis showed the highest inflammation levels, followed by osteoarthritis, then joint trauma, with different immune cell types driving inflammation in each disease (granulocytes in trauma, macrophages/fibroblasts in OA, fibroblasts/plasma cells in RA). These distinct inflammatory phenotypes suggest that different joint conditions may require targeted anti-inflammatory treatments, potentially informing more personalized physiotherapy approaches and medication strategies for managing pain and inflammation in each specific type of joint disease.

CORR INSIGHTS®: WHAT GENERAL AND PAIN-ASSOCIATED PSYCHOLOGICAL DISTRESS PHENOTYPES EXIST AMONG PATIENTS WITH HIP AND KNEE OSTEOARTHRITIS?

I notice that the abstract for this paper is listed as "NA" (not available), which limits my ability to provide a comprehensive summary of the study's methods, findings, and implications.

Based solely on the title, this appears to be a CORR Insights commentary that examines different psychological distress patterns in patients with hip and knee osteoarthritis, specifically looking at both general psychological distress and pain-related distress as distinct phenotypes or subgroups.

Without the abstract content, I cannot accurately describe the study's specific methods, key findings about the identified phenotypes, or the practical implications for physiotherapy and patient management.

To provide you with a proper 3-4 sentence summary covering the study objective, methods, phenotype findings, and management implications, I would need access to the full abstract or paper content.

QUALITY COMPARISON BETWEEN TWO DIFFERENT TYPES OF PLATELET-RICH PLASMA FOR KNEE OSTEOARTHRITIS.

This study aimed to compare the quality and characteristics of two different types of platelet-rich plasma (PRP) treatments for knee osteoarthritis: autologous protein solution (APS) and leukocyte-poor PRP (LP-PRP). The researchers analyzed blood samples from 10 healthy volunteers and 16 knee osteoarthritis patients, measuring platelet and white blood cell counts, growth factors, and inflammatory markers in each PRP type.

The key finding was that the two PRP types had distinctly different compositions: APS contained more white blood cells and anti-inflammatory substances, while LP-PRP had higher levels of growth factors that promote healing. However, patients receiving APS injections experienced more joint pain that lasted longer compared to those receiving LP-PRP.

These results suggest that the preparation method significantly affects PRP quality and clinical outcomes, indicating that physiotherapists and clinicians should carefully consider the specific type of PRP being used when planning treatment protocols for knee osteoarthritis patients.

CHARACTERIZATION OF REGIONAL MENISCAL CELL AND CHONDROCYTE PHENOTYPES AND CHONDROGENIC DIFFERENTIATION WITH HISTOLOGICAL ANALYSIS IN OSTEOARTHRITIC DONOR-MATCHED TISSUES.

This study aimed to identify specific cellular markers that could objectively assess meniscus degeneration in knee osteoarthritis and evaluate the potential of different meniscal cells for tissue repair. Researchers used flow cytometry and histological analysis to examine cells from both damaged and healthier meniscal tissues in 10 patients with medial knee osteoarthritis, comparing cells from different regions (avascular vs vascular areas) and matching them with cartilage cells from the same donors.

The study identified distinct cellular "fingerprints" - meniscal cells showed higher levels of specific surface markers (CD49B, CD49C, CD166) compared to cartilage cells, and more severely degenerated meniscal tissue had elevated integrin proteins (CD49B, CD29), suggesting these could serve as objective measures of meniscal damage. Additionally, severely degenerated menisci showed structural changes including reduced blood vessel networks around important collagen fiber formations.

Importantly, the researchers found that meniscal cells from the lateral (less affected) meniscus in patients with medial knee osteoarthritis retained good capacity to develop into cartilage-like tissue in laboratory conditions. This suggests these cellular markers could help physiotherapists and clinicians better assess meniscal health objectively, while the discovery of viable repair cells from patients' own lateral meniscus offers potential for future regenerative treatments that could complement rehabilitation

TOTAL KNEE ARTHROPLASTY ACCORDING TO THE ORIGINAL KNEE PHENOTYPES WITH KINEMATIC ALIGNMENT SURGICAL TECHNIQUE-EARLY CLINICAL AND FUNCTIONAL OUTCOMES.

This study investigated how different knee shapes (phenotypes) affect outcomes after total knee replacement surgery using a technique that restores each patient's original knee alignment rather than forcing all knees into the same position. The researchers analyzed 140 knee replacements in 123 patients, categorizing knees into five types based on their original alignment (neutral, varus, or valgus) and tracking clinical outcomes for three years.

They found that most patients had varus-aligned knees (71%), followed by neutral (20%) and valgus alignment (9%), and that all phenotype groups achieved similar excellent functional improvements despite having different final alignments after surgery. The approach showed promising results with 99% of implants surviving at three years and no loosening problems, even in knees that maintained some varus alignment post-surgery.

These findings suggest that personalizing knee replacement surgery to match each patient's original knee shape may be more effective than using a one-size-fits-all approach, potentially leading to better outcomes and implant longevity. For physiotherapists, this indicates that post-surgical rehabilitation should also be tailored to individual knee phenotypes rather than expecting all patients to achieve identical alignment goals.

MENISCUS CELL REGIONAL PHENOTYPES: DEDIFFERENTIATION AND REVERSAL BY BIOMATERIAL EMBEDDING.

This laboratory study aimed to understand how meniscus cells from different regions of the knee cartilage behave and change when grown outside the body, and whether special materials could help maintain their natural characteristics. Researchers extracted cells from inner and outer zones of pig meniscus tissue and analyzed gene expression patterns using molecular techniques, comparing cells grown in standard laboratory conditions versus those embedded in specialized polymer gels (PEGDA/GELMA). The study identified specific cellular "signatures" that distinguish healthy meniscus cells from deteriorated ones, finding that cells lose their specialized properties when grown in standard conditions, but that embedding them in tunable polymer materials can help restore and maintain their natural characteristics. These findings could lead to improved tissue engineering approaches and regenerative treatments for meniscus injuries, potentially offering better alternatives to current limited surgical options and helping prevent the long-term joint degeneration that often follows meniscus damage.

MACROPHAGE PHENOTYPES AND MONOCYTE SUBSETS AFTER DESTABILIZATION OF THE MEDIAL MENISCUS IN MICE.

This study aimed to identify different types of immune cells (macrophage phenotypes) in joint tissue and blood following surgical destabilization of knee cartilage in mice, which is used to model osteoarthritis development. The researchers used a surgical procedure called destabilization of the medial meniscus (DMM) and compared results to sham-operated and normal knees, measuring immune cell markers and joint damage over 8 weeks using tissue staining and blood analysis techniques.

The key finding was that both surgically destabilized and sham-operated knees showed similar patterns of inflammatory immune cell activation, but only in the destabilized knees did these immune cells correlate with specific joint damage features like tissue thickening and bone spur formation. The study identified that joint instability combined with immune cell activation may be necessary to trigger osteoarthritis progression, rather than immune activation alone.

These findings suggest that osteoarthritis development requires both mechanical joint instability and immune system activation working together, which has important implications for physiotherapy approaches that focus on restoring joint stability and potentially managing inflammation simultaneously in early-stage osteoarthritis.

DETERMINATION OF PAIN PHENOTYPES IN KNEE OSTEOARTHRITIS USING LATENT PROFILE ANALYSIS.

This study aimed to identify distinct subgroups of people with knee osteoarthritis based on multiple factors including other health conditions, psychological distress, pain sensitivity, and knee function. Researchers used a statistical technique called latent profile analysis on data from 152 people with knee osteoarthritis, examining their leg strength, number of health conditions, pain catastrophizing (negative thoughts about pain), and pressure pain sensitivity at the knee.

The analysis revealed four distinct phenotypes: a high comorbidity group (9% of participants), a pain-sensitive/weak group with elevated pain sensitivity and quadriceps weakness (63%), a high pain catastrophizing group (11%), and a stronger/less pain-sensitive group (17%). The high comorbidity and high catastrophizing groups experienced worse pain and function, while the stronger group had lower pain sensitivity but higher rates of previous knee injuries.

These findings suggest that people with knee osteoarthritis fall into distinct subgroups that may benefit from different physiotherapy approaches - for example, targeting strength training for the weak group, pain education and coping strategies for the catastrophizing group, and managing multiple conditions for the high comorbidity group.

IMPACT OF DIFFERENT PHYSICAL ACTIVITY TYPES ON KNEE JOINT STRUCTURAL DEGENERATION ASSESSED WITH 3-T MRI IN OVERWEIGHT AND OBESE SUBJECTS: DATA FROM THE OSTEOARTHRITIS INITIATIVE.

This study aimed to determine how different types of physical activity affect knee joint deterioration over 4 years in 415 overweight and obese adults. Researchers used detailed MRI scans to track structural changes in knee joints while participants reported their regular participation in six activity types (ball sports, cycling, jogging, elliptical training, racquet sports, and swimming), which were also grouped as high- or low-impact activities.

The findings revealed distinct activity-related phenotypes: participants engaging in high-impact activities and racquet sports showed the greatest progression of knee joint damage, while those using elliptical trainers had the smallest increases in structural deterioration. Overall, most activity groups experienced some worsening of knee structure over the study period, but the rate varied significantly by activity type.

These results suggest that for overweight individuals with early-to-moderate knee osteoarthritis, physiotherapy and exercise recommendations should prioritize low-impact activities like elliptical training while carefully considering the risks of high-impact and racquet sports for long-term joint health.

A COMPARATIVE STUDY FOR DIFFERENT TYPES OF THUMB BASE OSTEOARTHRITIS INJECTIONS: A RANDOMIZED CONTROLLED INTERVENTIONAL STUDY.

This randomized controlled trial aimed to compare the effectiveness of three different injection treatments for thumb base osteoarthritis: platelet-rich plasma (PRP), hyaluronic acid (HA), and corticosteroids. The researchers studied 45 patients with thumb CMC joint OA, randomly dividing them into three equal groups and measuring pain, joint tenderness, hand function, and grip/pinch strength at 4 and 12 weeks after injection. All three injection types initially improved pain and function at 4 weeks, but only hyaluronic acid maintained these benefits at 12 weeks, while the PRP and steroid groups showed deterioration in outcomes. For clinical management, hyaluronic acid injections appear to offer the most sustained relief for thumb base OA patients, though physiotherapists should note that injection therapy may provide a window of opportunity for rehabilitation exercises while pain is reduced.

REOPERATIONS ARE FEW AND CONFINED TO THE MOST VALGUS PHENOTYPES 4 YEARS AFTER UNRESTRICTED CALIPERED KINEMATICALLY ALIGNED TKA.

This study examined alignment patterns (phenotypes) and reoperation rates in 198 patients who received kinematically aligned total knee replacement surgery, which aims to restore each patient's natural knee alignment rather than using a standard mechanical alignment approach. The researchers used CT scans to measure alignment angles in both the operated and non-operated legs, categorizing patients into different phenotypes based on their natural anatomy.

The key findings showed that only 1.5% of patients required reoperation at 4 years, with these few cases occurring exclusively in patients with more valgus (knock-kneed) alignment patterns due to kneecap-related problems. Importantly, the surgery successfully restored patients' natural alignment phenotypes to match their healthy opposite leg, and most patients achieved similar functional outcomes regardless of their alignment type.

These results suggest that kinematic alignment may be a viable alternative to traditional mechanical alignment for most patients, though those with more valgus phenotypes may need specialized implant designs or surgical techniques to reduce the risk of kneecap complications.

INCREASE OF AEROBIC GLYCOLYSIS MEDIATED BY ACTIVATED T HELPER CELLS DRIVES SYNOVIAL FIBROBLASTS TOWARDS AN INFLAMMATORY PHENOTYPE: NEW TARGETS FOR THERAPY?

This study investigated how immune T helper cells influence the metabolism and inflammatory behavior of synovial fibroblasts (joint lining cells) in rheumatoid arthritis and osteoarthritis. Researchers used laboratory techniques to measure glucose consumption, lactate production, and inflammatory molecule release when fibroblasts were exposed to signals from activated T helper cells, while testing various blocking treatments.

The key finding was that T helper cells pushed both rheumatoid arthritis and osteoarthritis fibroblasts toward a highly inflammatory state characterized by increased sugar breakdown (glycolysis) and production of inflammatory substances like IL-6 and tissue-damaging enzymes. Importantly, osteoarthritis fibroblasts could be transformed to behave more like aggressive rheumatoid arthritis cells when repeatedly exposed to T helper cell signals.

Blocking sugar metabolism pathways or JAK enzymes effectively reduced both the metabolic changes and inflammatory output of fibroblasts, unlike traditional cytokine-blocking treatments. This suggests that targeting cellular energy metabolism could offer new therapeutic approaches for treating joint inflammation in both rheumatoid arthritis and osteoarthritis, potentially informing future physiotherapy and rehabilitation strategies by addressing the underlying cellular drivers of joint tissue damage.

THE FUTURE OF DEEP PHENOTYPING IN OSTEOARTHRITIS: HOW CAN HIGH THROUGHPUT OMICS TECHNOLOGIES ADVANCE OUR UNDERSTANDING OF THE CELLULAR AND MOLECULAR TAXONOMY OF THE DISEASE?

This editorial discusses how advanced molecular technologies (called "omics") can help scientists better understand the different types of osteoarthritis at the cellular level. The authors argue that using multiple omics approaches together will allow researchers to identify distinct molecular patterns (endotypes) within osteoarthritis, moving beyond the current broad clinical categories to more precise disease classifications. The key finding emphasized is that osteoarthritis likely consists of multiple overlapping subtypes that can only be properly distinguished by examining cellular and molecular differences rather than just clinical symptoms. This deeper understanding of osteoarthritis subtypes could lead to more targeted treatments and better drug development, potentially addressing why many osteoarthritis medications have failed in clinical trials and improving personalized management approaches for patients.

RADIOGRAPHIC DIFFERENCES IN THE CONCOMITANT DEFORMITIES IN TWO TYPES OF MEDIAL ANKLE OSTEOARTHRITIS.

This study aimed to identify differences in foot and knee deformities between two distinct types of medial ankle osteoarthritis: varus angulation (ankle tilting) and medial translation (sideways shifting). Researchers analyzed weight-bearing X-rays from 102 patients, measuring various angles in the ankle, foot, and knee to compare deformity patterns between the two groups.

The study found that patients with varus angulation ankle arthritis had significantly different foot arch angles and knee alignment compared to those with medial translation, suggesting these represent distinct disease patterns with different associated deformities throughout the lower limb. The foot arch angle was the strongest factor distinguishing between the two types of ankle arthritis.

These findings suggest that ankle osteoarthritis should not be treated as a single condition, but rather as distinct subtypes that may require different treatment approaches, with careful assessment of the entire lower limb chain from knee to foot when planning surgical or conservative management strategies.

BIOMECHANICAL EVALUATION OF DIFFERENT TYPES OF LATERAL HINGE FRACTURES IN MEDIAL OPENING WEDGE HIGH TIBIAL OSTEOTOMY.

This study aimed to determine how different types of lateral hinge fractures affect the stability of high tibial osteotomy surgery, which is used to treat knee osteoarthritis by realigning the leg bones. Researchers tested 20 synthetic tibia bone models with different fracture patterns (intact hinge, Type I, II, and III fractures) under compression forces to measure stability, displacement, and strength after surgical fixation with plates.

The findings revealed distinct biomechanical phenotypes: Type I fractures behaved similarly to intact hinges with good stability, while Type III fractures showed significantly greater bone displacement and reduced strength, making them the most unstable fracture pattern. Type II fractures fell between these extremes in terms of mechanical properties.

These results have important implications for post-surgical rehabilitation, suggesting that patients with Type III lateral hinge fractures require more cautious management with delayed weight-bearing and potentially additional surgical fixation, while those with Type I fractures may follow standard rehabilitation protocols similar to patients without fractures.

ASSOCIATION BETWEEN ONCOSTATIN M EXPRESSION AND INFLAMMATORY PHENOTYPE IN EXPERIMENTAL ARTHRITIS MODELS AND OSTEOARTHRITIS PATIENTS.

This study investigated the role of oncostatin M (OSM), a specific inflammatory protein, in identifying different types of osteoarthritis (OA) patients and disease patterns. The researchers examined OSM levels in joint tissues from two different rat arthritis models and analyzed existing data from OA patients' joint fluid to compare those with and without detectable OSM. They found that OSM was associated with inflammation and bone spur formation in the inflammatory arthritis model, but was not elevated in the mechanical wear-and-tear OA model, and OA patients with detectable OSM had higher levels of other inflammatory markers in their joint fluid. These findings suggest that OSM could help identify an "inflammatory subtype" of OA patients, which may be important for physiotherapists and clinicians to recognize since these patients might benefit from different treatment approaches targeting inflammation rather than just mechanical factors.

A LOW CARTILAGE FORMATION AND REPAIR ENDOTYPE PREDICTS RADIOGRAPHIC PROGRESSION OF SYMPTOMATIC KNEE OSTEOARTHRITIS.

This study aimed to identify whether people with knee osteoarthritis who have low cartilage repair capacity are more likely to experience disease progression. Researchers measured PRO-C2, a blood marker reflecting cartilage formation, in 253 knee osteoarthritis patients across two cohorts and tracked joint space narrowing (cartilage loss) on X-rays over 24 months.

The study identified a distinct "low cartilage repair" subgroup of patients with very low PRO-C2 levels who showed significantly more joint space narrowing (0.65mm more loss) and had a 3.4-fold higher risk of radiographic progression compared to those with high PRO-C2 levels. Interestingly, patients in this low cartilage repair subgroup appeared to respond better to salmon calcitonin treatment, a medication that promotes cartilage formation.

These findings suggest that a simple blood test could help identify knee osteoarthritis patients at high risk of rapid progression, potentially allowing for earlier intervention with targeted treatments that support cartilage repair rather than standard management approaches.

CLINICAL RELEVANCE OF BIOCHEMICAL AND METABOLIC CHANGES IN OSTEOARTHRITIS.

This study aimed to examine how biochemical and metabolic changes in osteoarthritis (OA) can help identify different patient subgroups for more personalized treatment approaches. The researchers reviewed biochemical processes in cartilage breakdown and used metabolomics (studying small molecules in blood) to analyze different patterns in OA patients. They identified three distinct metabolic subgroups: 11% of patients had elevated butyryl carnitine levels, 33% had low arginine levels, and 56% showed changes in fat molecule processing. These findings suggest that OA patients could be categorized into specific biological subtypes based on their blood chemistry, which could lead to more targeted and personalized physiotherapy and medical treatments rather than using a one-size-fits-all approach.

EFFECTS OF VARIOUS TYPES OF ULTRASOUND THERAPY IN HIP OSTEOARTHRITIS - A DOUBLE-BLIND, RANDOMIZED, CONTROLLED, FOLLOW-UP STUDY.

This study aimed to compare the effectiveness of different ultrasound therapy approaches combined with conventional physiotherapy for treating hip osteoarthritis. Seventy-one patients were randomly assigned to receive either continuous ultrasound, pulsed ultrasound, ultrasound plus electrical stimulation (TENS), or fake ultrasound treatment, alongside standard care including exercise, massage, and water therapy. All treatment groups showed significant improvements in pain, walking ability, and quality of life at 3-month follow-up, with the ultrasound plus TENS group having the highest percentage (73%) of patients achieving meaningful functional improvement. However, since even the placebo ultrasound group improved similarly, the findings suggest that adding ultrasound therapy to conventional physiotherapy does not provide additional benefits for hip osteoarthritis patients, indicating that standard exercise-based treatment may be sufficient for managing this condition.

HOW FEASIBLE IS THE STRATIFICATION OF OSTEOARTHRITIS PHENOTYPES BY MEANS OF ARTIFICIAL INTELLIGENCE?

I apologize, but I cannot provide a summary of this research paper because the abstract is listed as "NA" (not available).

To write a meaningful summary focusing on the study objective, methods, findings regarding osteoarthritis phenotypes, and implications for physiotherapy management, I would need access to the actual abstract content that describes:

- The study's aims and research questions
- The artificial intelligence methods used for phenotype stratification
- The results showing different osteoarthritis subgroups identified
- The clinical implications for treatment approaches

If you could provide the full abstract, I would be happy to create a concise 3-4 sentence summary in plain language covering these key areas.

ARTICULAR CHONDROCYTE PHENOTYPE REGULATION THROUGH THE CYTOSKELETON AND THE SIGNALING PROCESSES THAT ORIGINATE FROM OR CONVERGE ON THE CYTOSKELETON: TOWARDS A NOVEL UNDERSTANDING OF THE INTERSECTION BETWEEN ACTIN DYNAMICS AND CHONDROGENIC FUNCTION.

This review study aimed to examine how the cellular skeleton (cytoskeleton) controls cartilage cell behavior and could be targeted for cartilage repair therapies. The authors analyzed existing research on how various factors like inflammation, growth signals, and osteoarthritis affect cartilage cells through cytoskeletal changes, particularly focusing on stress fiber formation within cells.

The key finding was that harmful conditions (inflammation, osteoarthritis progression) cause cartilage cells to lose their healthy characteristics by promoting the formation of stress fibers - rigid structures that make cells behave more like scar tissue rather than healthy cartilage. The authors identified specific molecular pathways (RhoA/ROCK signaling) that control this process, suggesting that when cells form more stress fibers, they produce less healthy cartilage components like collagen type II.

These findings suggest that future osteoarthritis treatments and physiotherapy approaches should consider targeting the balance between stress fiber formation and breakdown in cartilage cells, potentially through mechanical loading strategies or therapies that promote healthy cell shape and function.

PHENOTYPIC ALTERATION OF MACROPHAGES DURING OSTEOARTHRITIS: A SYSTEMATIC REVIEW.

This systematic review examined how immune cells called macrophages change during osteoarthritis (OA) development, analyzing 28 studies from human tissues and animal experiments. The researchers found that inflammatory M1-type macrophages increase in both joint tissues and blood circulation during OA, while anti-inflammatory M2-type macrophages decrease. However, the traditional classification of macrophages into just M1 and M2 types showed conflicting results across studies, suggesting this simple categorization may be inadequate for understanding OA. These findings indicate that targeting macrophage behavior could offer new treatment approaches for OA, but more detailed classification systems and advanced research methods are needed before developing specific therapies or rehabilitation strategies.

BACK TO BASICS: TRANSCRIPTOMICS STUDIES FOR DEEP PHENOTYPING OF OSTEOARTHRITIS.

I apologize, but I cannot provide a meaningful summary of this research paper because the abstract is listed as "NA" (not available).

To write an accurate summary focusing on the study objective, methods, findings regarding osteoarthritis phenotypes/subgroups, and implications for physiotherapy management, I would need access to the actual abstract content.

If you could provide the complete abstract, I would be happy to create a 3-4 sentence summary in plain language that addresses all the key points you've requested regarding this transcriptomics study on osteoarthritis phenotyping.

DISCOVERY OF BONE MORPHOGENETIC PROTEIN 7-DERIVED PEPTIDE SEQUENCES THAT ATTENUATE THE HUMAN OSTEOARTHRITIC CHONDROCYTE PHENOTYPE.

This study aimed to discover small peptide sequences from bone morphogenetic protein 7 (BMP7) that could restore healthy cartilage cell function in osteoarthritis. Researchers screened a library of BMP7 peptide fragments and tested the most promising candidates on cartilage cells from OA patients, as well as in a rat model of joint injury. Two specific peptide sequences (P[63-82] and P[113-132]) successfully reversed the diseased cartilage cell characteristics back toward a healthy state, with effects lasting up to 8 days after a single treatment, and one peptide reduced cartilage breakdown in the animal model. These findings suggest that targeted peptide therapy could offer a new disease-modifying treatment approach for OA, potentially helping to restore cartilage health rather than just managing pain symptoms, which could complement physiotherapy approaches focused on joint preservation and function.

MOVING TOWARD TARGETING THE RIGHT PHENOTYPE WITH THE RIGHT PLATELET-RICH PLASMA (PRP) FORMULATION FOR KNEE OSTEOARTHRITIS.

This review aimed to explore how different osteoarthritis (OA) phenotypes respond to platelet-rich plasma (PRP) injections and identify strategies for personalizing treatment approaches. The authors analyzed existing literature on PRP effectiveness across different patient subgroups, focusing on inflammatory characteristics, imaging findings, and injection techniques to understand why treatment responses vary so widely between patients.

The key finding is that patients with inflammatory OA phenotypes may be the best candidates for PRP therapy, as PRP releases substances that can reduce inflammation and interact with immune cells in the joint. Current research shows PRP works better in early-stage knee OA, and combining standard joint injections with targeted injections into bone lesions or damaged ligaments may improve outcomes.

The implications for physiotherapy and management include the need to identify inflammatory OA patients through clinical examination and imaging before offering PRP treatment, rather than using a one-size-fits-all approach. This personalized strategy could help physiotherapists and clinicians better select which patients are likely to benefit from PRP injections and potentially combine them with targeted rehabilitation programs.

ALPHA-DEFENSINS DETERMINATION IN DIFFERENT TYPES OF SYNOVIAL FLUID AND PARALLEL COLLECTED SERUM SAMPLES BY ELISA.

This study aimed to establish reference ranges for alpha-defensins (HNP1-3) in blood and joint fluid samples and evaluate their ability to distinguish between different types of joint inflammation. Researchers collected synovial fluid and blood samples from 92 patients and categorized them into groups including non-inflammatory (including osteoarthritis), inflammatory non-infectious, inflammatory infectious, and hemorrhagic conditions, then measured defensin levels using laboratory assays.

The study identified distinct defensin concentration patterns across different joint conditions, with inflammatory conditions showing significantly higher levels than non-inflammatory states like osteoarthritis, and found strong correlations between defensin levels and other inflammatory markers like interleukin-6. Alpha-defensins demonstrated promise as biomarkers that can reliably differentiate inflammatory joint diseases from non-inflammatory conditions such as osteoarthritis.

For physiotherapy practice, these findings suggest that alpha-defensin testing could help clinicians better identify which patients have inflammatory versus non-inflammatory joint conditions, potentially leading to more targeted treatment approaches and better patient phenotyping for personalized rehabilitation strategies.

LINKING CHONDROCYTE AND SYNOVIAL TRANSCRIPTIONAL PROFILE TO CLINICAL PHENOTYPE IN OSTEOARTHRITIS.

This study aimed to determine how gene expression patterns in osteoarthritis joint tissues relate to different patient characteristics and whether molecular subtypes can be reliably identified. Researchers analyzed RNA sequencing data from cartilage and synovium samples of 113 osteoarthritis patients using advanced computational methods to identify distinct gene expression patterns and link them to clinical features.

The study identified two distinct patient subgroups in early-stage cartilage damage, with one subgroup showing high inflammation that was more common in women and patients taking certain stomach medications (proton pump inhibitors). The researchers also developed a simple seven-gene test that could accurately classify patients into these molecular subtypes, which was successfully validated in a separate group of patients.

These findings suggest that osteoarthritis patients can be reliably classified into molecular subtypes based on tissue gene expression, which could lead to more personalized treatment approaches rather than the current "one-size-fits-all" management of osteoarthritis.

THE ROLE OF METABOLOMICS IN PRECISION MEDICINE OF OSTEOARTHRITIS: HOW FAR ARE WE?

This narrative review examined how metabolomics (the study of chemical processes in the body) could help develop personalized medicine approaches for osteoarthritis patients. The researchers reviewed 32 population-based studies that analyzed metabolic markers in blood, joint fluid, cartilage, or bone samples from people with osteoarthritis. The studies identified key metabolic pathways disrupted in osteoarthritis, including energy production, amino acid processing, and fat metabolism, which could potentially be used to classify patients into different biological subgroups (endotypes). While still early-stage research, metabolomics shows promise for better understanding osteoarthritis causes, identifying patient subgroups, and developing targeted treatments, though more research is needed before these findings can guide clinical practice or physiotherapy approaches.

DIFFERENT PHENOTYPES AND CHONDROGENIC RESPONSES OF HUMAN MENSTRUAL BLOOD AND BONE MARROW MESENCHYMAL STEM CELLS TO ACTIVIN A AND TGF-Β3.

This study aimed to compare two different types of stem cells - those from menstrual blood (MenSCs) and bone marrow (BMMSCs) - to see how well they could develop into cartilage-forming cells when treated with growth factors called Activin A and TGF-β3. The researchers isolated stem cells from healthy donors and tested their characteristics, growth rates, and ability to form cartilage both in laboratory dishes and when implanted into mice.

The study found that these two stem cell types behave quite differently - menstrual blood stem cells grew faster and had different surface markers, while bone marrow stem cells responded better to TGF-β3 alone for cartilage formation. Importantly, menstrual blood stem cells showed enhanced cartilage development when both Activin A and TGF-β3 were used together, whereas bone marrow stem cells did not respond the same way to this combination.

These findings suggest that different stem cell sources require tailored approaches with specific growth factor combinations to optimize cartilage formation. For future osteoarthritis treatments, this research indicates that menstrual blood stem cells could potentially offer an easier-to-obtain alternative to bone marrow stem cells for cartilage repair therapies, but the treatment protocols would need to be specifically designed for each cell type's unique characteristics.

THE LONG PENTRAXIN PTX3: A NOVEL SERUM MARKER TO IMPROVE THE PREDICTION OF OSTEOPOROSIS AND OSTEOARTHRITIS BONE-RELATED PHENOTYPES.

This study aimed to investigate whether PTX3 (a protein involved in bone metabolism) could serve as a blood marker to identify bone-related disease patterns in osteoporosis and osteoarthritis patients. Researchers measured PTX3 levels in blood samples from 32 osteoporosis patients, 19 osteoarthritis patients, and 25 healthy controls using laboratory testing, then analyzed how well PTX3 could distinguish between healthy and diseased individuals. The results showed that both osteoporosis and osteoarthritis patients had significantly higher PTX3 levels compared to healthy controls, and PTX3 demonstrated excellent accuracy in identifying these conditions. These findings suggest that PTX3 blood testing could potentially help clinicians better identify and classify different bone-related disease patterns, which may lead to more targeted treatment approaches in musculoskeletal rehabilitation and patient management.

PHENOTYPIC CLASSIFICATION OF KNEE OSTEOARTHRITIS ACCORDING TO PAIN MECHANISMS; A CLINICAL OBSERVATIONAL STUDY.

This study aimed to identify different pain mechanisms in knee osteoarthritis patients and determine how often neuropathic pain and psychological factors contribute to their symptoms. The researchers evaluated 104 knee osteoarthritis patients using questionnaires to assess neuropathic pain features and pain catastrophizing, then compared these measures across groups with different pain intensities and X-ray severity levels.

The study found that 16% of patients showed signs of neuropathic pain, 34% demonstrated catastrophic thinking, while 64% appeared to have only typical joint-related (nociceptive) pain. Importantly, patients with less severe X-ray changes but high pain levels were more likely to show catastrophic thinking, while neuropathic pain features couldn't be predicted from X-ray severity or pain intensity alone.

These findings suggest that physiotherapists should assess pain mechanisms beyond just looking at X-rays and pain levels, as patients may need different treatment approaches - with those showing catastrophic thinking potentially benefiting from psychological interventions alongside traditional joint-focused treatments.

ANALYSIS OF HIP JOINT LOADING DURING WALKING WITH DIFFERENT SHOE TYPES USING INSTRUMENTED TOTAL HIP PROSTHESES.

This study aimed to determine how different types of footwear affect forces and moments acting on the hip joint after total hip replacement surgery. Researchers used special instrumented hip prostheses to directly measure joint loads while patients walked on a treadmill wearing various shoe types compared to walking barefoot. The findings revealed that most shoes increased hip joint loading, with everyday shoes and men's dress shoes causing the largest increases (30-47% higher forces), while barefoot-style shoes had minimal impact on joint loads. These results suggest that patients recovering from hip surgery or managing hip osteoarthritis should consider wearing flexible, low-profile shoes rather than stiff-soled or heavily cushioned footwear to reduce stress on their hip joints during rehabilitation and daily activities.

CHONDROCYTES FROM OSTEOARTHRITIC AND CHONDROCALCINOSIS CARTILAGE REPRESENT DIFFERENT PHENOTYPES.

This study aimed to compare chondrocyte (cartilage cell) characteristics between osteoarthritis (OA) patients and those with chondrocalcinosis (CC), a condition involving calcium crystal deposits in cartilage. Researchers analyzed cartilage samples from CC patients, severe OA patients, and healthy donors using imaging, tissue staining, and genetic analysis to identify different cellular phenotypes and crystal effects.

The study identified two distinct phenotypes: OA cartilage showed increased hypertrophic (enlarged, dysfunctional) chondrocytes with basic calcium phosphate (BCP) crystals, while CC cartilage exhibited cellular senescence (aging) markers associated with calcium pyrophosphate dihydrate (CPPD) crystals. BCP crystals actively promoted chondrocyte hypertrophy, whereas CPPD crystals induced cellular senescence rather than hypertrophy.

These findings suggest that OA and CC represent different disease pathways requiring distinct management approaches - targeting hypertrophic processes in traditional OA versus addressing cellular senescence in chondrocalcinosis-related joint problems. For physiotherapy practice, this indicates that patients with crystal-associated joint disease may need different treatment strategies depending on their specific crystal type and underlying cellular phenotype.

ASSESSMENT OF COMMON COMORBIDITY PHENOTYPES AMONG OLDER ADULTS WITH KNEE OSTEOARTHRITIS TO INFORM INTEGRATED CARE MODELS.

This study aimed to identify common patterns of health conditions (comorbidity phenotypes) among older adults with knee osteoarthritis to improve care coordination. The researchers analyzed Medicare claims data from over 200,000 beneficiaries with knee osteoarthritis, comparing them to matched controls without osteoarthritis, and used statistical modeling to identify distinct subgroups based on their health conditions. They found four main phenotypes: low comorbidity (53% of patients), hypothyroid/osteoporosis (27%), vascular disease (10%), and high medical/psychological comorbidity (10%), with people with knee osteoarthritis having notably higher rates of other musculoskeletal conditions and chronic pain. These findings suggest that nearly half of older adults with knee osteoarthritis have complex health needs requiring coordinated care from multiple providers, indicating that traditional single-provider treatment approaches may be inadequate and supporting the need for integrated, personalized care models in physiotherapy and rehabilitation.

SPACEFLIGHT AND HIND LIMB UNLOADING INDUCES AN ARTHRITIC PHENOTYPE IN KNEE ARTICULAR CARTILAGE AND MENISCI OF RODENTS.

This study aimed to investigate how reduced weight-bearing affects knee cartilage and meniscus health by examining rodents exposed to spaceflight or simulated weightlessness through hind limb unloading (HLU). Researchers used multiple techniques including microCT scanning, tissue analysis, and protein studies to assess cartilage and meniscus changes in mice after various durations of actual spaceflight or ground-based unloading, followed by recovery periods with or without exercise.

The study identified a specific "arthritic phenotype" characterized by cartilage degradation at key weight-bearing contact points, reduced meniscus volume, decreased protective molecules (glycosaminoglycans), and increased breakdown enzymes and oxidative stress. Both actual spaceflight and simulated weightlessness produced similar patterns of joint deterioration, with damage occurring as early as 13 days.

These findings suggest that prolonged periods of reduced weight-bearing (whether from space travel, bed rest, or sedentary behavior) can rapidly induce arthritis-like changes in knee joints. However, the study also demonstrated that exercise during recovery periods helped restore cartilage volume and thickness, highlighting the critical importance of weight-bearing exercise in maintaining joint health and potentially reversing disuse-related joint damage in physiotherapy programs.

CORRECTION TO: THE LONG PENTRAXIN PTX3: A NOVEL SERUM MARKER TO IMPROVE THE PREDICTION OF OSTEOPOROSIS AND OSTEOARTHRITIS BONERELATED PHENOTYPES.

I cannot provide a meaningful summary of this research paper because this appears to be a correction notice rather than a full research article. The title indicates it is a "CORRECTION TO" a previous study about PTX3 (a protein marker) and its potential to predict bone-related conditions like osteoporosis and osteoarthritis. However, without access to the actual abstract or correction details, I cannot determine what the original study's objectives, methods, findings, or clinical implications were. To provide you with the requested 3-4 sentence summary focusing on phenotyping and rehabilitation implications, I would need access to either the original paper's abstract or the content of this correction.

DEEP LEARNING FOR LARGE SCALE MRI-BASED MORPHOLOGICAL PHENOTYPING OF OSTEOARTHRITIS.

This study aimed to use artificial intelligence to identify different structural patterns (phenotypes) in knee MRI scans that could predict osteoarthritis development. Researchers trained deep learning computer models to classify nearly 5,000 knee MRIs into four distinct phenotypes: bone, meniscus/cartilage, inflammatory, and hypertrophy patterns, achieving high accuracy (89-96%) in identifying these different structural features. The key finding was that people without existing osteoarthritis who had bone or hypertrophy phenotypes were 3-6 times more likely to develop osteoarthritis within four years, with most phenotypes also predicting eventual knee replacement surgery. This AI-based phenotyping approach could help physiotherapists and clinicians identify high-risk patients earlier for targeted prevention strategies and help researchers select appropriate participants for clinical trials testing new osteoarthritis treatments.

ASSOCIATIONS BETWEEN THE RADIOGRAPHIC PHENOTYPES AND THE PRESENCE OF METABOLIC SYNDROME IN PATIENTS WITH KNEE OSTEOARTHRITIS.

This study investigated whether different X-ray patterns of knee osteoarthritis are linked to metabolic syndrome (a cluster of conditions including high blood pressure, abnormal cholesterol, and excess belly fat). The researchers compared 100 women over 40 with knee osteoarthritis, dividing them into two groups based on their dominant X-ray features: joint space narrowing (where the cartilage gap appears reduced) versus osteophyte formation (bone spurs). The key finding was that metabolic syndrome was significantly more common in patients with the joint space narrowing pattern compared to those with mainly bone spurs, particularly in women without diabetes (76% versus 48%). This suggests that patients with joint space narrowing-dominant knee osteoarthritis may benefit from integrated management approaches that address both their joint symptoms and metabolic health factors like weight management, blood pressure control, and cardiovascular risk reduction alongside traditional physiotherapy interventions.

MIDTERM FOLLOW-UP RESULTS OF TWO DIFFERENT TYPES OF IMPLANTS IN OPENING WEDGE HIGH TIBIA OSTEOTOMY.

This retrospective study aimed to compare the medium-term outcomes of two different implant types used in opening wedge high tibial osteotomy, a surgical procedure for knee osteoarthritis. Researchers analyzed 241 knees over an average 6-year follow-up period, comparing precountered non-locking plates (PP) with precountered locking plates (LP), and examining both single-plane and two-plane bone cuts.

The study found that locking plates (LP) performed significantly better than non-locking plates (PP), with higher survival rates at both 5 years (80% vs 68%) and 10 years (64% vs 49%), and lower revision rates (26% vs 47%). Additionally, among locking plate cases, the two-plane cutting technique showed better outcomes than the single-plane technique, with lower reoperation rates (16% vs 37%).

These findings suggest that implant choice and surgical technique create distinct patient subgroups with different prognoses following high tibial osteotomy. For physiotherapists managing post-surgical rehabilitation, patients with non-locking plates or single-plane cuts may require more cautious loading progressions and closer monitoring, as they face higher risks of complications and revision surgery.

COMMENT ON MOVING TOWARD TARGETING THE RIGHT PHENOTYPE WITH THE RIGHT PLATELET-RICH PLASMA FORMULATION FOR KNEE OSTEOARTHRITIS.

I notice that the abstract is listed as "NA" (not available), which makes it impossible to provide an accurate summary of the study's objective, methods, findings, and implications.

Based solely on the title, this appears to be a commentary piece discussing the importance of matching specific platelet-rich plasma (PRP) formulations to particular osteoarthritis phenotypes in knee patients. However, without the actual abstract content, I cannot provide details about the study's methodology, key findings regarding patient subgroups, or specific implications for physiotherapy management.

To provide you with a meaningful summary, I would need access to the full abstract or additional content from this publication.

CORRELATION BETWEEN PATIENT-REPORTED OUTCOME MEASURES AND HEALTH INSURANCE PROVIDER TYPES IN PATIENTS WITH HIP OSTEOARTHRITIS.

This study examined whether insurance type is associated with baseline patient-reported outcome scores in nearly 6,000 patients with hip osteoarthritis. The researchers analyzed multiple outcome measures (HOOS-PS, PROMIS physical function, and PROMIS global mental/physical scores) across different insurance groups using statistical analyses to compare baseline scores.

The study identified distinct subgroups based on insurance type, with patients using commercial insurance consistently reporting the best function and health scores, while Medicaid patients reported the poorest scores across all measures - differences that were clinically meaningful. The Medicaid group also had more diverse demographics, lower income, and higher rates of medical complications, while workers' compensation patients showed particularly poor mental health scores.

These findings suggest that insurance type may serve as a marker for different patient phenotypes in hip osteoarthritis, reflecting underlying socioeconomic and health disparities. For physiotherapy practice, this highlights the importance of considering patients' insurance status and associated factors when interpreting outcome scores and setting realistic treatment expectations, as baseline function varies significantly between insurance groups.

GLOBAL SINGLE CLUSTERING OF PHENOTYPE-ASSOCIATED HUMAN AGING GENES IN THE CO-EXPRESSION AND PHYSICAL INTERACTION NETWORKS: AN OMIM-BASED INVESTIGATIVE REVIEW.

This study investigated how human aging-related genes cluster together in biological networks to better understand aging mechanisms. The researchers used the OMIM database to identify 286 validated aging genes associated with 96 age-related conditions (including osteoarthritis, neurodegenerative disorders, and cancers), then analyzed how these genes interact using network analysis tools and compared them to randomly selected control genes.

The key finding was that aging-related genes formed a single, tightly connected cluster in both gene co-expression and protein interaction networks, unlike control genes which formed multiple separate clusters. Three hub genes (TP53, APP, and SIRT1) were consistently important across multiple human tissues commonly affected by aging.

For osteoarthritis management and physiotherapy, this suggests that aging-related joint degeneration may share common biological pathways with other age-related conditions, potentially opening opportunities for treatments that target these shared mechanisms rather than treating osteoarthritis in isolation. The identification of key hub genes could also inform future research into biomarkers or therapeutic targets for age-related musculoskeletal conditions.

DRIVERS OF PHENOTYPIC VARIATION IN CARTILAGE: CIRCADIAN CLOCK GENES.

This review examined how circadian clock genes influence cartilage health and contribute to different osteoarthritis phenotypes. The authors analyzed existing research on what happens when clock genes are deleted or overexpressed in cartilage cells (chondrocytes), focusing on resulting abnormalities in cartilage, bone, and joint lining tissue. They found that disruptions to natural daily rhythms in activity, movement, eating, and body temperature can accelerate joint damage and lead to distinct disease patterns in conditions like osteoarthritis and rheumatoid arthritis. These findings suggest that managing daily routines and circadian rhythms could be important considerations in physiotherapy and rehabilitation programs for people with joint diseases, potentially helping to slow cartilage breakdown and optimize treatment timing.

THE DEVELOPMENT OF DISEASE-MODIFYING THERAPIES FOR OSTEOARTHRITIS (DMOADS): THE EVIDENCE TO DATE.

This review examines the development of disease-modifying osteoarthritis drugs (DMOADs), which aim to slow or halt disease progression rather than just treat symptoms. The authors analyzed clinical trials of targeted therapies designed for three main osteoarthritis subtypes: cartilage-driven disease (focusing on cartilage breakdown), bone-driven disease (targeting bone changes), and inflammation-driven disease (addressing joint inflammation). The review found that despite understanding these different disease patterns, no DMOADs have yet received regulatory approval, with many clinical trials failing to demonstrate effectiveness. The findings suggest that successful osteoarthritis management may require personalized treatment approaches that match specific therapies to individual patient subtypes, which could inform physiotherapy strategies by helping identify which patients might benefit from particular exercise or treatment approaches.

SEVEN PHENOTYPES OF VARUS OSTEOARTHRITIC KNEES CAN BE IDENTIFIED IN THE CORONAL PLANE.

This study aimed to determine if distinct structural patterns (phenotypes) exist in varus osteoarthritic knees that could guide surgical planning, challenging the assumption that all varus knees are similar. Researchers analyzed over 2,100 full-leg X-rays, measuring various bone angles and alignment parameters in the knee, thigh, and shin bones. They identified seven distinct types of varus knees, grouped into four main phenotypes: "neutral" knees with near-normal bone shapes (11%), "intra-articular varus" with bone loss within the joint (38%), "extra-articular varus" with deformities outside the joint (41%), and "valgoid type" with some characteristics typically seen in knock-kneed patients (9%). These findings suggest that knee osteoarthritis treatment and rehabilitation should be individualized based on each patient's specific bone structure and deformity pattern, rather than using a one-size-fits-all approach for surgical procedures like knee replacement or corrective bone cuts.

MECHANICAL ALIGNMENT FOR PRIMARY TKA MAY CHANGE BOTH KNEE PHENOTYPE AND JOINT LINE OBLIQUITY WITHOUT INFLUENCING CLINICAL OUTCOMES: A STUDY COMPARING RESTORED AND UNRESTORED JOINT LINE OBLIQUITY.

This study aimed to determine whether restoring patients' original knee alignment patterns (phenotypes) during total knee arthroplasty would improve clinical outcomes compared to using standard mechanical alignment techniques. The researchers analyzed 1,078 knees using detailed X-ray measurements to classify different knee phenotypes based on joint angles and joint line obliquity (how tilted the knee joint appears), then compared clinical scores between patients whose original knee patterns were restored versus those who weren't.

The study found that standard mechanical alignment techniques changed most patients' original knee phenotypes, with only 18% having their natural alignment pattern restored after surgery. While patients who had their tilted joint line pattern restored experienced slightly less pain, the difference was too small to be clinically meaningful, and overall functional outcomes were similar between groups.

These findings suggest that current "one-size-fits-all" knee replacement techniques may not be optimal since they alter patients' natural knee patterns without clear clinical benefit. For physiotherapists and surgeons, this highlights the potential importance of developing more personalized surgical approaches that consider individual patients' original knee alignment patterns, though more research is needed to determine if this would actually improve rehabilitation outcomes and long-term function.

MICRORNA-486 PROMOTES A MORE CATABOLIC PHENOTYPE IN CHONDROCYTE-LIKE CELLS BY TARGETING SIRT6 : POSSIBLE INVOLVEMENT IN CARTILAGE DEGRADATION IN OSTEOARTHRITIS.

This study investigated how microRNA-486 (miR-486) contributes to cartilage breakdown in osteoarthritis by examining its effects on cartilage cell behavior. Researchers used laboratory techniques to measure miR-486 levels in cartilage samples from people with severe osteoarthritis compared to controls, and tested how manipulating miR-486 levels affected cartilage-producing cells in culture. They found that miR-486 was significantly elevated in severely arthritic cartilage and promoted a destructive cell phenotype by increasing enzymes that break down cartilage (MMP-13, ADAMTS4) while decreasing protective cartilage components (collagen, aggrecan) through targeting a protective protein called SIRT6. These findings suggest that miR-486 could serve as a potential therapeutic target for osteoarthritis treatment, though this early-stage research would need translation into clinical interventions before impacting physiotherapy or patient management approaches.

PATHOLOGY-PAIN RELATIONSHIPS IN DIFFERENT OSTEOARTHRITIS ANIMAL MODEL PHENOTYPES: IT MATTERS WHAT YOU MEASURE, WHEN YOU MEASURE, AND HOW YOU GOT THERE.

This study aimed to determine whether osteoarthritis (OA) pain characteristics and underlying mechanisms differ between distinct disease phenotypes using two different mouse models. Researchers compared mice with surgically-induced OA (DMM model) versus inflammation-induced OA (AIA model), measuring various pain behaviors and nerve gene expression over 16 weeks, alongside joint damage assessment.

The key finding was that despite both models developing similar joint damage, they showed completely different pain patterns and nerve responses - the AIA model had more early pain and weight-bearing problems, while the DMM model developed different types of pain sensitivity and movement issues later in the disease. Importantly, the molecular mechanisms in the nerve cells and the relationship between joint damage and pain were unique to each model, suggesting distinct OA phenotypes exist even in animal studies.

These findings suggest that OA patients likely have different underlying pain mechanisms depending on how their disease developed, which could explain why people with similar-looking joint damage on scans can have vastly different pain experiences. This supports the need for personalized physiotherapy and pain management approaches that consider individual patient phenotypes rather than using one-size-fits-all treatments for OA.

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I notice there's a mismatch between your request and the provided abstract. You've asked me to analyze a study about osteoarthritis phenotyping and musculoskeletal rehabilitation, but the abstract you've provided is about chemical compounds isolated from a mold strain and their potential therapeutic effects.

The provided abstract describes a biochemical study that identified 17 different compounds from a specific mold strain, characterized their chemical structures using various analytical methods, and tested some compounds for anti-inflammatory and neuroprotective effects. Two compounds showed promise for reducing inflammation in cartilage cells and protecting nerve cells from chemotherapy-related damage. While the study suggests potential applications for osteoarthritis treatment, it doesn't involve patient phenotyping, subgroup identification, or rehabilitation strategies.

Could you please provide the correct abstract about osteoarthritis phenotyping and musculoskeletal rehabilitation that you'd like me to summarize?

EDITORIAL: CELL-BASED APPROACHES FOR MODULATING CARTILAGE AND BONE PHENOTYPE.

I apologize, but I cannot provide a meaningful summary of this research paper because the abstract is not available (marked as "NA").

To write an accurate summary focusing on the study objective, methods, findings about phenotypes/subgroups, and implications for physiotherapy management, I would need access to the paper's abstract or full content.

If you could provide the abstract text or key details from the paper, I would be happy to create a concise 3-4 sentence summary in plain language that addresses the specific aspects you've requested regarding osteoarthritis phenotyping and musculoskeletal rehabilitation.

FUNCTIONAL KNEE PHENOTYPES OF OA PATIENTS UNDERGOING TOTAL KNEE ARTHROPLASTY ARE SIGNIFICANTLY MORE VARUS OR VALGUS THAN IN A NON-OA CONTROL GROUP.

This study aimed to compare knee alignment patterns (phenotypes) in patients with severe osteoarthritis requiring total knee replacement versus people without osteoarthritis. The researchers used computer navigation during surgery to precisely measure various knee angles in 504 osteoarthritis patients and compared these measurements to published data from a non-arthritic control group.

The key finding was that only 12.7% of osteoarthritis patients had normal overall knee alignment compared to 24.7% of the control group, with osteoarthritis patients showing much more variation toward either knock-knee (valgus) or bow-legged (varus) positions. Gender differences emerged, with males more likely to develop inward-angled thigh bones (femoral varus) and females more prone to outward-angled thigh bones (femoral valgus).

These findings suggest that severe osteoarthritis is associated with distinct structural knee phenotypes that differ significantly from normal anatomy, which could inform more personalized approaches to both surgical planning and earlier physiotherapy interventions aimed at addressing alignment-specific movement patterns before joint replacement becomes necessary.

OXIDATIVE STRESS IS ASSOCIATED WITH CHARACTERISTIC FEATURES OF THE DYSFUNCTIONAL CHRONIC PAIN PHENOTYPE.

This study investigated whether oxidative stress (cellular damage from harmful molecules) is linked to a specific type of chronic pain called the "dysfunctional chronic pain phenotype" - a subgroup of pain patients with particularly severe symptoms across multiple areas. Researchers measured pain, psychological factors, and function in 84 osteoarthritis patients before knee replacement surgery, and analyzed their blood for markers of oxidative stress using advanced laboratory techniques. They found that patients with higher oxidative stress levels had more intense and widespread pain, greater depression and catastrophic thinking about pain, more pain interference with daily activities, and poorer physical function. These findings suggest that oxidative stress may be a key biological mechanism underlying this severe chronic pain subgroup, potentially opening up new treatment approaches such as antioxidant therapies or lifestyle interventions that reduce oxidative stress, though more research is needed to develop specific clinical applications.

INSURANCE TYPE AND PATIENT-REPORTED OUTCOME MEASURES: CAN INSURANCE TYPE BE A GOOD PROXY FOR RISK STRATIFICATION?: COMMENTARY ON AN ARTICLE BY BRADY D. GREENE, BS, ET AL.: "CORRELATION BETWEEN PATIENT-REPORTED OUTCOME MEASURES AND HEALTH INSURANCE PROVIDER TYPES IN PATIENTS WITH HIP OSTEOARTHRITIS".

I cannot provide a meaningful summary of this research as no abstract was provided. The title suggests this is a commentary piece examining whether insurance type could be used to predict patient outcomes and stratify risk in hip osteoarthritis patients, but without the abstract or full text, I cannot determine the study's specific methods, findings about patient subgroups, or clinical implications for physiotherapy management. To write an accurate summary focusing on phenotyping and rehabilitation implications, I would need access to the actual content of the commentary and the original research it discusses.

EFFECTS OF LONG-TERM EXERCISE AND A HIGH-FAT DIET ON SYNOVIAL FLUID METABOLOMICS AND JOINT STRUCTURAL PHENOTYPES IN MICE: AN INTEGRATED NETWORK ANALYSIS.

This study aimed to understand how diet and exercise influence knee osteoarthritis development by examining the connections between systemic factors, joint fluid chemistry, and joint structure in mice. Researchers fed mice either normal or high-fat diets for nearly a year, with half also having access to running wheels, then analyzed joint tissues, blood markers, and synovial fluid metabolites using advanced chemical analysis and network mapping.

The study identified distinct osteoarthritis phenotypes: high-fat diet mice developed moderate osteoarthritis with cartilage damage and bone changes linked to systemic inflammation and glucose problems, while exercise had minimal direct effects on joint structure but created different metabolic patterns in the joint fluid. Importantly, obesity strengthened connections between joint fluid chemistry and blood sugar/inflammation markers, whereas exercise strengthened connections between joint fluid and bone structure changes.

These findings suggest that obesity-related and exercise-related osteoarthritis may represent different disease subtypes requiring tailored management approaches - with obesity-related cases potentially benefiting more from metabolic and anti-inflammatory interventions, while exercise-related changes may require focus on bone health and mechanical loading strategies.

IDENTIFYING THE PHENOTYPIC AND TEMPORAL HETEROGENEITY OF KNEE OSTEOARTHRITIS: DATA FROM THE OSTEOARTHRITIS INITIATIVE.

This study aimed to identify distinct knee osteoarthritis (KOA) subtypes and understand how they progress differently over time, addressing limitations of previous research that either grouped patients by severity alone or assumed all knees follow the same progression pattern. The researchers analyzed data from 678 knees over 48 months using a specialized model called SUSTAIN that can identify both subtypes and their unique progression sequences based on various biological markers.

The study found three distinct KOA subtypes affecting 15%, 61%, and 24% of knees respectively, each with its own characteristic progression pattern of biological changes over time. Interestingly, knees with the same X-ray severity grade (Kellgren-Lawrence grades 0-4) were distributed across different subtypes and stages, suggesting that traditional severity grading doesn't capture the full picture of disease variation.

These findings suggest that effective knee osteoarthritis management and physiotherapy should be tailored to specific subtypes and disease stages rather than relying solely on X-ray severity, potentially leading to more personalized and effective treatment approaches.

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This study investigated whether CD146-positive T cells, which are known to produce IL-17, are enriched in psoriatic arthritis (PsA) joint inflammation. Researchers used high-dimensional flow cytometry to analyze T cell populations in synovial fluid and blood from patients with PsA, rheumatoid arthritis (RA), and osteoarthritis (OA), focusing on CD146 expression and IL-17 production in memory T cells. The main finding was that CD146-positive effector T cells were specifically enriched in the inflamed synovial tissue of PsA patients compared to other arthritis types. This suggests that PsA represents a distinct inflammatory phenotype characterized by accumulation of these IL-17-producing cells, which could inform targeted therapeutic approaches focusing on this specific T cell subset rather than general anti-inflammatory treatments.

VARIATIONS AND CHARACTERISTICS OF THE VARIOUS CLINICAL PHENOTYPES IN A COHORT OF NIGERIAN SICKLE CELL PATIENTS.

This study aimed to characterize the different clinical presentations (phenotypes) of sickle cell disease in a cohort of 270 Nigerian adult patients. The researchers collected clinical and laboratory data over 10 years from outpatients, documenting various complications and their frequencies across different patient subgroups. Key findings showed that leg ulcers were most common (68 patients), followed by priapism in males (43), bone death/avascular necrosis (42), kidney problems (31), bone infections (23), and osteoarthritis (15), with notable variations in complication patterns compared to other populations. These findings suggest that genetic and environmental factors influence how sickle cell disease manifests in different patients, which has important implications for developing personalized treatment approaches and rehabilitation strategies, particularly for the significant musculoskeletal complications like osteoarthritis and avascular necrosis that would benefit from targeted physiotherapy interventions.

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This study investigated whether cartilage cells (chondrocytes) from osteoarthritis patients can adopt different inflammatory profiles similar to immune cells. Researchers exposed chondrocytes from knee replacement patients to four different inflammatory signals (IFNγ, IL-1β, IL-4, and IL-17) and analyzed gene expression changes using advanced sequencing techniques. The results revealed four distinct chondrocyte phenotypes: IL-1β created the most inflammatory profile with over 2,800 gene changes related to cartilage breakdown, while IFNγ, IL-17, and IL-4 each produced unique but less extensive inflammatory patterns. These findings suggest that cartilage cells can switch between different functional states during osteoarthritis progression, potentially opening new treatment approaches that target specific inflammatory pathways rather than using one-size-fits-all therapies.

MODELING IN VITRO OSTEOARTHRITIS PHENOTYPES IN A VASCULARIZED BONE MODEL BASED ON A BONE-MARROW DERIVED MESENCHYMAL CELL LINE AND ENDOTHELIAL CELLS.

This study aimed to develop a laboratory model of osteoarthritis (OA) that includes both bone and blood vessel components to better understand how the disease develops beneath joint cartilage. Researchers created artificial bone tissue using stem cells and endothelial cells, then exposed it to inflammatory substances or fluid from damaged cartilage to mimic the OA environment. The experiments revealed two distinct disease patterns: inflammatory substances caused both abnormal blood vessel growth and bone changes (increased mineral loss and collagen production), while damaged cartilage fluid primarily affected bone without altering blood vessel formation. This research suggests there may be different pathways leading to OA development, which could help physiotherapists and clinicians better understand why patients respond differently to treatments and potentially guide the development of more targeted therapies for managing osteoarthritis.

CROSS-VALIDATION OF GOOD VERSUS POOR SELF-REPORTED OUTCOME TRAJECTORY TYPES FOLLOWING KNEE ARTHROPLASTY.

This study aimed to validate whether distinct "good" versus "poor" recovery patterns after knee replacement surgery, previously identified in one group of patients, could be replicated in a completely independent group of 926 UK patients. The researchers used advanced statistical modeling to track patient-reported knee function over 12 months after surgery, comparing their findings to a previous study that used different outcome measures.

The analysis successfully confirmed that patients fall into two distinct recovery trajectories - those with good outcomes and those with poor outcomes - suggesting these represent real, consistent patterns rather than chance findings. Pain catastrophizing (tendency to focus on and magnify pain experiences) emerged as the only reliable predictor of poor outcomes across both studies, while other factors like comorbidities showed inconsistent predictive value.

These findings suggest that physiotherapists and clinicians can reliably identify patients at risk of poor recovery after knee replacement by assessing their pain-related thoughts and coping strategies, enabling targeted interventions to address catastrophic thinking patterns before and after surgery.

OA FOUNDATIONS - EXPERIMENTAL MODELS OF OSTEOARTHRITIS.

This review aimed to improve how researchers select and use animal models for osteoarthritis research by better matching experimental models to specific human patient groups. The authors analyzed existing animal models of osteoarthritis and proposed a framework focusing on study objectives, alignment between animal models and human OA subtypes, and available resources, culminating in an experimental design checklist. The key finding emphasizes that osteoarthritis shows diverse phenotypes in both humans and animal models, but researchers rarely consider which specific human patient subgroup their chosen animal model actually represents. This approach has important implications for developing more targeted treatments, as better alignment between experimental models and specific patient phenotypes should lead to therapies that are more effective for particular subgroups of people with osteoarthritis, potentially improving physiotherapy and rehabilitation outcomes through more personalized interventions.

UNIQUE SERUM IMMUNE PHENOTYPES AND STRATIFICATION OF OKLAHOMA NATIVE AMERICAN RHEUMATIC DISEASE PATIENTS.

This study aimed to identify better biomarkers for diagnosing rheumatic diseases in Native American populations, who have higher disease rates and often present with atypical symptoms that make diagnosis challenging. Researchers used machine learning to analyze blood samples from 158 Native American patients with various rheumatic conditions (including rheumatoid arthritis, osteoarthritis, and other autoimmune diseases) and healthy controls, measuring immune system proteins and inflammatory markers.

The analysis identified five distinct immune phenotypes among patients based on their blood biomarker patterns, which did not align with traditional diagnostic categories. Patients with low inflammation and stronger immune regulation had fewer symptoms, while those with active T-cell immune pathways experienced more joint inflammation and arthritis symptoms.

These findings suggest that personalized treatment approaches based on individual immune profiles, rather than traditional diagnostic labels alone, could improve care for Native American patients with rheumatic diseases, potentially leading to earlier diagnosis and more targeted physiotherapy and medical interventions.

BMP7 REDUCES THE FIBROCARTILAGE CHONDROCYTE PHENOTYPE.

This study investigated whether BMP7 (bone morphogenetic protein 7) can reduce the harmful fibrocartilage chondrocyte phenotype that contributes to osteoarthritis progression. Researchers treated cartilage cells from 18 patients with end-stage osteoarthritis with BMP7 and measured changes in fibrosis-related genes and proteins using various laboratory techniques. The results showed that BMP7 successfully reduced the fibrocartilage phenotype by decreasing collagen type I levels and blocking pro-fibrotic signaling pathways, while increasing enzymes that break down excess collagen. These findings suggest BMP7 could be a promising disease-modifying treatment for osteoarthritis since it targets both the fibrotic and hypertrophic cell types that drive cartilage destruction, potentially offering new therapeutic options beyond current symptom management approaches.

SYNOVIAL TISSUE FROM SITES OF JOINT PAIN IN KNEE OSTEOARTHRITIS PATIENTS EXHIBITS A DIFFERENTIAL PHENOTYPE WITH DISTINCT FIBROBLAST SUBSETS.

This study aimed to determine whether synovial tissue from painful areas in knee osteoarthritis (OA) patients contains different fibroblast cell subsets compared to non-painful sites, and to compare these differences between early and end-stage disease. Researchers analyzed synovial tissue samples from 51 knee OA patients using advanced single-cell RNA sequencing, combined with patient pain mapping and MRI assessment of synovitis.

The study identified distinct synovial fibroblast phenotypes at sites where patients reported pain, with different cellular characteristics in early versus end-stage OA. Fibroblasts from painful areas promoted inflammation, tissue scarring (fibrosis), and nerve growth and activity, with early OA painful sites showing particularly strong effects on nerve cell survival and growth.

These findings suggest that pain in knee OA involves specific cellular mechanisms at localized sites within the joint, rather than being a general joint-wide phenomenon. This research could lead to more targeted treatments for OA pain, potentially including localized therapies directed at specific fibroblast subsets, which may inform more precise physiotherapy approaches and pain management strategies.

SONIC HEDGEHOG INDUCES MESENCHYMAL STROMAL CELL SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE AND CHONDROCYTE APOPTOSIS IN HUMAN OSTEOARTHRITIC CARTILAGE.

This study aimed to understand how Sonic Hedgehog (SHH) signaling contributes to osteoarthritis (OA) development by investigating its effects on different cell types in cartilage. The researchers used human cartilage samples to examine gene expression patterns and conducted laboratory experiments treating cells with SHH protein and analyzing the resulting cellular changes.

The key finding was that SHH acts through two harmful mechanisms in OA cartilage: it causes mesenchymal stromal cells to become senescent (aged) and release inflammatory substances, while simultaneously triggering cartilage cell death. This creates a destructive cycle where aged stromal cells produce SHH, which promotes inflammation and cartilage breakdown, identifying distinct cellular phenotypes involved in OA progression.

These findings suggest that targeting SHH signaling could be a promising therapeutic approach for OA management, potentially informing the development of treatments that could slow cartilage degeneration and reduce inflammation in affected joints.

BLOOD AND URINE BIOMARKERS IN OSTEOARTHRITIS - AN UPDATE ON CARTILAGE ASSOCIATED TYPE II COLLAGEN AND AGGRECAN MARKERS.

This narrative review aimed to evaluate blood and urine biomarkers derived from cartilage proteins (type II collagen and aggrecan) for osteoarthritis research and clinical application. The authors reviewed existing literature on biomarkers that measure cartilage breakdown and formation processes in osteoarthritis patients. Key findings showed that while several biomarkers (like UCTX-II) have been validated for assessing disease severity and tracking treatment responses, current biomarkers cannot effectively identify distinct osteoarthritis subgroups or molecular subtypes (endotypes) needed for personalized care. The review highlights that despite progress in understanding cartilage metabolism through biomarkers, significant gaps remain in developing practical diagnostic tools that could help physiotherapists and clinicians tailor treatments to specific patient phenotypes.

TARGETED PHOSPHOLIPIDOMIC ANALYSIS OF SYNOVIAL FLUID AS A TOOL FOR OSTEOARTHRITIS DEEP PHENOTYPING.

This study aimed to identify specific phospholipid patterns in knee joint fluid that could help classify different types and stages of osteoarthritis. Researchers used advanced mass spectrometry to analyze joint fluid from 15 osteoarthritis patients (with early and late-stage disease) and 4 healthy controls, then applied statistical methods to identify distinct molecular profiles.

The analysis successfully distinguished between healthy individuals and both early and late-stage osteoarthritis patients, with osteoarthritis patients showing elevated levels of various phospholipids including phosphatidylcholines. Importantly, the researchers identified two distinct subtypes of early-stage osteoarthritis based on their unique phospholipid signatures, and found that certain phospholipids were linked to cartilage damage severity.

These findings suggest that analyzing joint fluid chemistry could help physiotherapists and clinicians better categorize osteoarthritis patients into specific subtypes, potentially leading to more personalized treatment approaches and rehabilitation programs tailored to each patient's biological profile.

EMERGING CONCEPTS OF ENDOTYPES/PHENOTYPES IN REGENERATIVE MEDICINE FOR OSTEOARTHRITIS.

This paper discusses applying phenotype/endotype concepts to improve patient selection for regenerative medicine treatments in osteoarthritis. The authors present a conceptual framework rather than empirical research, drawing on existing knowledge that osteoarthritis encompasses different conditions with varying clinical presentations, causes, and underlying disease mechanisms (endotypes). The key finding is that regenerative medicine has shown inconsistent results partly because treatments are not matched to appropriate patient subgroups, similar to challenges faced in drug trials for disease-modifying osteoarthritis treatments. The authors argue that better molecular endotype understanding could help identify which patients are likely to respond to expensive regenerative therapies versus those who should proceed directly to joint replacement surgery, potentially reducing healthcare costs and improving treatment outcomes through more personalized approaches.

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This study investigated the genetic basis of osteoarthritis by examining a family with a specific mutation in the COMP gene (c.1358C>T, p.Asn453Ser). The researchers used genetic screening, molecular dynamics simulation, and clinical phenotyping to analyze three family members carrying the same mutation. The key finding was that this single COMP mutation produced three distinct joint-related phenotypes: idiopathic early-onset osteoarthritis (index case), multiple epiphyseal dysplasia with secondary osteoarthritis (brother), and peripheral inflammatory arthritis without osteoarthritis or dysplasia (sister). These results demonstrate significant phenotypic variability from the same genetic mutation, suggesting that COMP mutations can cause a broader spectrum of joint disorders than previously recognized, which has important implications for genetic counseling and may require tailored rehabilitation approaches based on the specific phenotype rather than the underlying genetic cause alone.

IRREGULAR TYPES OF PROXIMAL TIBIOFIBULAR JOINT INCREASE THE RISK OF TOTAL KNEE REPLACEMENT: DATA FROM THE OSTEOARTHRITIS INITIATIVE.

This study investigated whether different shapes of the proximal tibiofibular joint (PTFJ) - a small joint on the outer side of the knee - influence the likelihood of needing knee replacement surgery in people with progressive osteoarthritis. Using a nested case-control design from the Osteoarthritis Initiative, researchers analyzed MRI images from 193 participants who underwent total knee replacement and matched controls, classifying PTFJ shapes into three categories: plane, trochoid, and irregular types.

The study found that people with "irregular" PTFJ shapes at baseline were 62% more likely to require knee replacement surgery compared to those with regular joint shapes (35.8% vs 26.9% prevalence in cases vs controls). This association was significant at baseline but not at later time points closer to surgery, suggesting that PTFJ morphology represents an early structural risk factor rather than a progressive change.

These findings suggest that PTFJ shape could serve as an additional phenotyping tool to identify patients at higher risk for severe knee osteoarthritis progression, potentially informing early intervention strategies and personalized physiotherapy approaches focused on optimizing knee biomechanics and joint loading patterns.

THE ROLE OF CALCIUM CRYSTALS AND THEIR EFFECT ON OSTEOARTHRITIS PATHOGENESIS.

This review examines how calcium crystals contribute to osteoarthritis (OA) disease mechanisms and define distinct patient subgroups. The authors analyzed existing literature on two main crystal types: basic calcium phosphate (BCP) and calcium pyrophosphate (CPP) crystals, which form based on different metabolic pathways involving phosphate balance. The study identifies that calcium crystal-related subtypes affect approximately 60% of OA patients, with BCP crystals linked to severe cartilage degradation and CPP crystals associated with age-related joint changes, though both can coexist in mixed presentations. These findings suggest that identifying crystal-related OA phenotypes could help tailor treatment approaches, though the authors note that whether crystals drive disease progression or result from cartilage breakdown remains unclear, indicating a need for phenotype-specific management strategies in clinical practice.

PHENOTYPIC CHARACTERISATION AND ASSOCIATIONS OF LEG ULCERS IN ADULT SICKLE CELL PATIENTS.

I notice there may be a mismatch between your request and the provided abstract. You've asked for a summary focused on osteoarthritis phenotyping and musculoskeletal rehabilitation, but this study examines sickle cell leg ulcers, which is primarily a vascular complication rather than a musculoskeletal condition.

Here's a summary of the actual study:

This study aimed to characterize the clinical features and associations of sickle leg ulcers (SLU) in adult sickle cell disease patients compared to those without ulcers. The researchers analyzed 272 sickle cell patients, identifying clinical characteristics and complications in the 68 patients (25%) who developed leg ulcers near the ankle area. Key findings showed that leg ulcers were significantly more common in males and strongly associated with pulmonary hypertension, though patients with ulcers didn't necessarily exhibit other severe disease features and had a relatively young median age of 25 years. The results suggest that sickle leg ulcers may represent a distinct disease phenotype that requires specific monitoring for pulmonary complications, though the study notes that environmental factors need further investigation to better understand ulcer development.

Would you like me to provide a different analysis, or did you perhaps intend to share a different abstract related to osteoarthritis?

INSIGHTS INTO THE MOLECULAR LANDSCAPE OF OSTEOARTHRITIS IN HUMAN TISSUES.

This review examined recent advances in osteoarthritis research using molecular profiling technologies (genomics, proteomics, metabolomics) to better understand disease mechanisms at the tissue level. The authors reviewed studies published since 2019 that used high-resolution techniques like single-cell analysis and multi-omics approaches to characterize different tissues and disease stages in osteoarthritis. Key findings revealed that osteoarthritis involves complex interactions between multiple tissues (cartilage, bone, synovium) and inflammatory processes, with molecular profiling identifying at least two distinct disease subtypes or "endotypes" based on biological signatures. These molecular insights into osteoarthritis phenotypes could potentially lead to more personalized treatment approaches and targeted therapies, though the review doesn't specify direct implications for current physiotherapy practice.

VALGUS ARTHRITIC KNEES CAN BE CLASSIFIED INTO NINE PHENOTYPES.

This study aimed to determine whether distinct anatomical phenotypes exist in valgus arthritic knees to support individualized surgical planning and classification for outcome studies. Researchers analyzed full-leg weight-bearing radiographs from 233 knees, measuring eight different angular parameters including hip-knee-ankle angle, valgus correction angle, and various femoral and tibial alignment measures. The analysis identified nine distinct phenotypes that could be grouped into four broad types: Type 1 "neutral knees" (12.5%) with near-normal alignment, Type 2 "intra-articular valgus" (22.7%) showing lateral compartment bone loss, Type 3 "extra-articular valgus" (35.2%) with deformity outside the joint, and Type 4 "varus-type" (29.6%) displaying characteristics typically seen in varus knees despite overall valgus alignment. This classification system could help surgeons better plan corrective osteotomies and optimize component positioning in knee replacement surgery, while also providing a framework for categorizing patients in clinical outcome studies and potentially guiding physiotherapy approaches based on specific deformity patterns.

PREVALENCE OF SYMPTOMATIC AXIAL OSTEOARTHRITIS PHENOTYPES IN SPAIN AND ASSOCIATED SOCIO-DEMOGRAPHIC, ANTHROPOMETRIC, AND LIFESTYLE VARIABLES.

This Spanish population-based study (EPISER2016) aimed to estimate the prevalence of symptomatic axial osteoarthritis phenotypes and identify associated patient characteristics in adults aged 40 and older. Using telephone screening questionnaires in a large, randomly selected sample, researchers examined two phenotypes: non-exclusive axial OA (NEA-OA, occurring with other joint involvement) and exclusive axial OA (EA-OA, affecting only the spine).

The study found that NEA-OA affected 19.17% of the population, with prevalence increasing substantially with age (3.6 times higher in those 80+ versus 40-49 years), higher BMI, female sex, and lower education levels, while lumbar involvement was more common than cervical OA. These findings represent the first European data on axial OA phenotype prevalence and suggest that age, obesity, and demographic factors significantly influence disease patterns.

For clinical management, these results highlight the need for targeted screening and prevention strategies, particularly for older adults and those with elevated BMI, while the high prevalence underscores the importance of developing specialized physiotherapy approaches for axial OA that consider patient age, weight status, and spinal region involvement.

NOVEL ROLE OF ESTROGEN RECEPTOR-Α ON REGULATING CHONDROCYTE PHENOTYPE AND RESPONSE TO MECHANICAL LOADING.

This study investigated why some cartilage areas remain preserved while others become damaged in the same osteoarthritic knee joint, specifically examining the role of estrogen receptor-α (ERα) in cartilage health and mechanical loading responses. The researchers used RNA sequencing to compare preserved versus damaged cartilage from OA patients, followed by gene manipulation experiments and mechanical compression testing in 3D cell culture models, with findings validated in animal studies.

Key findings revealed that ERα levels were significantly lower in damaged compared to preserved cartilage, and that reducing ERα expression promoted harmful cellular aging and OA-related changes in cartilage cells, while increasing ERα levels partially reversed these damaging effects. Importantly, mechanical overloading suppressed ERα levels and worsened cartilage deterioration, particularly when ERα was already reduced.

These results suggest that ERα acts as a protective factor in cartilage that helps cells respond appropriately to mechanical stress, indicating that therapies aimed at enhancing ERα levels could represent a novel treatment approach for osteoarthritis and may inform rehabilitation strategies regarding optimal loading patterns for preserving cartilage health.

RNA-SEQ DRIVEN EXPRESSION AND ENRICHMENT ANALYSIS TO INVESTIGATE CVD GENES WITH ASSOCIATED PHENOTYPES AMONG HIGH-RISK HEART FAILURE PATIENTS.

I notice there may be a mismatch between your request and the provided abstract. You've asked me to focus on osteoarthritis phenotyping and musculoskeletal rehabilitation, but the abstract is about cardiovascular disease and heart failure genetics.

**Study Summary:**

This study aimed to identify genetic biomarkers for cardiovascular disease (CVD) and heart failure by analyzing gene expression patterns in high-risk patients. The researchers used RNA sequencing on blood samples from adult CVD patients (including those with comorbid conditions like osteoarthritis) compared to healthy controls. The analysis revealed 4,885 differentially expressed genes, with 15 being significantly associated with heart failure and CVD, including four known genes (FLNA, CST3, LGALS3, and HBA1), and identified gender- and ethnicity-specific expression patterns. These findings could lead to improved diagnostic tools and personalized treatment approaches for CVD patients, potentially addressing current gaps in gender-specific biomarker thresholds that may contribute to underdiagnosis in women and overdiagnosis in men.

*Note: While osteoarthritis was mentioned as a comorbid condition in the patient population, this study focused primarily on cardiovascular genetics rather than musculoskeletal phenotyping or rehabilitation implications.*

OSTEOARTHRITIS IN YEAR 2021: BIOCHEMICAL MARKERS.

This systematic review aimed to summarize recent advances in protein-based soluble biomarkers for osteoarthritis by examining clinical studies published between January 2020 and March 2021. The authors systematically searched PubMed, identifying 48 relevant studies from 1,971 publications, with 16 selected for detailed narrative review and classified using the BIPEDS framework (covering burden of disease, investigative, prognostic, efficacy, diagnostic, and safety applications). The key finding was that current biomarker research is increasingly focused on identifying molecular endotypes and clinical phenotypes of osteoarthritis, with studies spanning disease burden assessment (2 papers), prognosis (4 papers), treatment efficacy monitoring (3 papers), and diagnosis/phenotyping (5 papers). The authors conclude that this biomarker-driven approach to phenotyping should enable more personalized and targeted management strategies for osteoarthritis patients, which has important implications for tailoring physiotherapy interventions and clinical trial design.

WORKING TOWARD MECHANISTIC PAIN PHENOTYPING IN OSTEOARTHRITIS.

I notice that the abstract is listed as "NA" (not available) for this paper. Without the abstract content, I cannot provide a meaningful summary of the study's methods, findings, or clinical implications.

To write an accurate summary focusing on the study objective, key methods, phenotyping findings, and management implications, I would need access to the full abstract or paper content.

If you could provide the abstract text or key details from the paper, I'd be happy to create a concise clinical summary for osteoarthritis researchers and clinicians.

NEUROPATHIC PAIN IN THE IMI-APPROACH KNEE OSTEOARTHRITIS COHORT: PREVALENCE AND PHENOTYPING.

This study aimed to identify and characterize a distinct osteoarthritis phenotype by comparing knee OA patients with likely neuropathic pain to those without this pain component. Using baseline data from a large cohort study, researchers matched 24 patients with high neuropathic pain scores (painDETECT ≥19) to 48 patients with low scores (≤12) who had similar overall knee and general pain levels, then compared their joint damage, pain patterns, and physical function.

The key finding revealed a paradoxical phenotype: patients with likely neuropathic pain had significantly less radiographic joint damage in their knees but worse physical function and more widespread pain affecting hips and hands. This suggests that in this subgroup, joint structural damage is not the primary driver of pain and disability, indicating a central pain processing dysfunction rather than local tissue damage.

These findings have important implications for treatment approaches, as patients with this neuropathic pain phenotype are unlikely to respond to standard pain medications or disease-modifying osteoarthritis drugs that target joint structure, and may require specialized neuropathic pain management strategies instead.

YAP/TAZ: KEY PLAYERS FOR RHEUMATOID ARTHRITIS SEVERITY BY DRIVING FIBROBLAST LIKE SYNOVIOCYTES PHENOTYPE AND FIBRO-INFLAMMATORY RESPONSE.

**Study Summary:**

This study investigated the role of YAP/TAZ proteins (transcriptional regulators) in driving disease severity and fibroblast behavior in rheumatoid arthritis (RA). Researchers used cell cultures from RA and osteoarthritis patients, 3D tissue models, and animal studies to examine how YAP/TAZ activity affects synovial cell behavior and tested whether blocking these proteins with verteporfin could reduce inflammation.

The key finding was that YAP/TAZ proteins were highly active in RA (19-fold increase in target gene expression), driving aggressive fibroblast behavior including increased proliferation, invasion, and inflammatory responses that distinguish RA from osteoarthritis phenotypes. Importantly, YAP/TAZ activity created tissue stiffening that formed a self-perpetuating cycle, maintaining chronic inflammation over time.

Blocking YAP/TAZ activity restored normal cell behavior in RA fibroblasts and significantly reduced arthritis severity in animal models (arthritic index decreased from 3.1 to 2.0). This suggests that YAP/TAZ inhibition could represent a novel therapeutic target for managing inflammatory arthritis, potentially offering new treatment approaches beyond current anti-inflammatory strategies.

CLINICAL PHENOTYPE AND MUSCULOSKELETAL CHARACTERISTICS OF PATIENTS WITH AGGRECAN DEFICIENCY.

This study aimed to characterize the musculoskeletal phenotype and joint health outcomes in patients with aggrecan deficiency caused by ACAN gene mutations. The researchers conducted comprehensive assessments of 22 individuals from nine families, including clinical examinations, gait analysis, patient-reported outcomes, and imaging studies to evaluate joint pathology across different age groups.

The study identified distinct age-related phenotypes: children typically presented with subtle skeletal changes and clinically silent joint disease (though 25% had osteochondritis dissecans), while adults showed severe joint deterioration with 90% having osteoarthritis or osteochondritis dissecans and 60% requiring orthopedic surgery. Progressive height decline was observed, with adults showing more severe short stature than children, and joint pathology increased significantly with age.

These findings suggest that aggrecan deficiency represents a progressive musculoskeletal condition requiring early identification and proactive management to optimize joint health and quality of life, with implications for developing age-specific monitoring and intervention strategies in physiotherapy and orthopedic care.

FEASIBILITY AND SUSTAINABILITY OF WORKING IN DIFFERENT TYPES OF JOBS AFTER TOTAL HIP ARTHROPLASTY: ANALYSIS OF LONGITUDINAL DATA FROM TWO COHORTS.

This study investigated return-to-work rates and job sustainability among working-age adults following total hip arthroplasty (THA), using questionnaire data from two cohorts with at least 5 years follow-up. The researchers analyzed 825 participants (mean age 58) to examine employment patterns and used survival analysis to identify risk factors for work cessation due to hip-related difficulties.

The study identified distinct occupational phenotypes based on physical demands, with process/plant operatives and elementary occupation workers showing much higher non-return rates (36-41%) compared to the overall 93% return-to-work rate. Workers exposed to prolonged standing (>4 hours/day), kneeling/squatting, or heavy lifting (≥10kg) had 3-5 times higher risk of eventually leaving work due to hip problems.

These findings suggest that rehabilitation programs should be tailored to specific occupational demands, with intensive functional training for workers in physically demanding roles, while some patients may benefit from job modification counseling or redeployment discussions as part of their post-THA care plan.

RESTORATION OF THE PHENOTYPE OF DEDIFFERENTIATED RABBIT CHONDROCYTES BY SESQUITERPENE FARNESOL.

This study investigated whether farnesol, a sesquiterpene compound, could restore the healthy phenotype in dedifferentiated rabbit chondrocytes (cartilage cells that have lost their normal characteristics). The researchers used cell culture methods to examine how farnesol affected collagen and glycosaminoglycan (GAG) production in chondrocytes that had become dedifferentiated either through repeated cell passages or inflammatory stimulation with interleukin-1β.

Key findings showed that farnesol successfully restored chondrocyte phenotype by increasing production of healthy collagen type II (2.5-fold) and GAGs (2.5-15 fold increase), while reducing harmful collagen types I and X and decreasing inflammatory markers like prostaglandin E2. The study identified that dedifferentiated chondrocytes represent a distinct phenotypic subgroup characterized by altered morphology, reduced SOX9 expression, and impaired matrix production - all of which were improved by farnesol treatment.

These results suggest farnesol could serve as a potential therapeutic agent for osteoarthritis treatment, though clinical applications for physiotherapy and rehabilitation would require further research to determine optimal delivery methods and dosing protocols for human patients.

PHENOTYPIC AND FUNCTIONAL PROPERTIES OF DEDIFFERENTIATED FAT CELLS DERIVED FROM INFRAPATELLAR FAT PAD.

This study aimed to investigate whether dedifferentiated fat cells (DFATs) can be isolated from the infrapatellar fat pad (IFP) in osteoarthritis patients and compare their properties to subcutaneous-derived DFATs. Researchers isolated mature adipocytes from IFP and subcutaneous tissue of 7 osteoarthritis patients, cultured them using ceiling culture methods, and analyzed the resulting DFATs through flow cytometry, gene expression profiling, and differentiation assays. Both IFP-derived and subcutaneous-derived DFATs showed similar stem cell characteristics and tri-lineage differentiation potential, but IFP-DFATs demonstrated significantly higher proliferative capacity and superior chondrogenic (cartilage-forming) differentiation ability. These findings suggest that IFP-DFATs may represent a more promising cell source for cartilage regeneration therapies in osteoarthritis management, potentially offering advantages over subcutaneous fat-derived cells for future regenerative treatments.

THE IMPORTANCE OF JOINT LINE OBLIQUITY: A RADIOLOGICAL ANALYSIS OF RESTRICTED BOUNDARIES IN NORMAL KNEE PHENOTYPES TO INFORM SURGICAL DECISION MAKING IN KINEMATICALLY ALIGNED TOTAL KNEE ARTHROPLASTY.

This study aimed to determine optimal restricted boundaries for kinematically aligned total knee arthroplasty (TKA) by analyzing how different alignment restrictions affect the ability to restore normal knee anatomy in 500 healthy knees. Researchers measured key alignment angles (hip-knee-ankle angle and joint line obliquity parameters) on radiographs and tested various boundary scenarios to see what proportion of normal knee variations would be captured.

The key finding was that restricting joint line obliquity had a major limiting effect on restoring normal knee anatomy - while ±3° boundaries captured 74% of knees when only hip-knee-ankle alignment was restricted, this dropped to just 36% when joint line obliquity was also restricted to the same boundaries. Among published alignment protocols, the most inclusive boundaries (allowing -6° to +3° for hip-knee-ankle angle and 84°-93° for joint line angles) captured 85% of normal knee variations.

These findings suggest that overly restrictive joint line obliquity boundaries significantly limit surgeons' ability to restore patients' natural knee anatomy during kinematically aligned TKA. For clinical practice, this indicates that alignment protocols should use boundaries centered around population means and avoid overly narrow restrictions on joint line obliquity to better accommodate the natural variation in knee phenotypes.

EEG THETA AND BETA BANDS AS BRAIN OSCILLATIONS FOR DIFFERENT KNEE OSTEOARTHRITIS PHENOTYPES ACCORDING TO DISEASE SEVERITY.

This cross-sectional study investigated how brain wave patterns measured by EEG relate to different clinical presentations in 66 people with chronic knee osteoarthritis pain. Using multivariate regression models, researchers analyzed brain oscillations across different frequency bands (delta, theta, alpha, beta) and brain regions to identify associations with pain, function, and disease severity.

The study identified two distinct neurophysiological phenotypes: patients with severe osteoarthritis and high pain showed increased beta brain waves in frontal-central areas and reduced theta activity, suggesting maladaptive brain compensation mechanisms, while those with milder disease and less pain demonstrated higher theta oscillation power. Additionally, the researchers found that low-frequency brain waves (delta/theta) were linked to cognitive impairment, aging, and depression, while higher alpha/beta activity over sensorimotor areas appeared to compensate for poor motor function and joint degeneration.

These findings suggest that brain wave patterns could serve as biomarkers to identify different osteoarthritis phenotypes and pain mechanisms, potentially enabling clinicians and physiotherapists to develop more personalized treatment approaches based on neurophysiological profiles rather than relying solely on traditional clinical measures.

ASSESSMENT OF CLINICAL, TISSUE, AND CELL-LEVEL METRICS IDENTIFY FOUR BIOLOGICALLY DISTINCT KNEE OSTEOARTHRITIS PATIENT PHENOTYPES.

This study aimed to identify distinct knee osteoarthritis (OA) patient subgroups by analyzing clinical, tissue, and cellular characteristics, and to determine predictors of disease severity and cartilage stem cell concentration. Researchers collected cartilage, synovium, and fat pad tissues from 90 patients undergoing knee replacement surgery and used clustering analysis to examine patient demographics, imaging findings, tissue quality, and concentrations of connective tissue progenitor cells across different joint tissues.

The analysis revealed four biologically distinct OA phenotypes: two younger, higher BMI groups with healthier cartilage (differing in stem cell concentrations across tissues), and two older, lower BMI groups with more diseased cartilage (showing opposite patterns of stem cell distribution between cartilage and surrounding tissues). Age, joint space narrowing, radiographic severity scores, cartilage quality markers, and synovium-derived cell concentration were identified as significant predictors of OA severity.

These findings suggest that OA patients can be classified into distinct biological subgroups based on age, BMI, cartilage health, and stem cell distribution patterns, which could enable more personalized treatment approaches and help physiotherapists and clinicians tailor rehabilitation strategies to specific patient phenotypes.

THE EXPRESSION OF INFLAMMASOMES NLRP1 AND NLRP3, TOLL-LIKE RECEPTORS, AND VITAMIN D RECEPTOR IN SYNOVIAL FIBROBLASTS FROM PATIENTS WITH DIFFERENT TYPES OF KNEE ARTHRITIS.

This study investigated molecular markers in synovial fibroblasts to identify distinct inflammatory patterns across different types of knee arthritis, including rheumatoid arthritis (RA), osteoarthritis (OA), early arthritis (EA), and controls. Researchers extracted synovial fibroblasts from knee surgery patients and analyzed the expression of inflammatory receptors (NLRP1, NLRP3, toll-like receptors) and vitamin D receptor using molecular techniques, with and without inflammatory stimulation.

The study identified distinct phenotypic differences between arthritis types: RA synovial fibroblasts showed significantly lower expression of NLRP1 and toll-like receptors compared to other arthritis forms when stimulated, while NLRP3 expression correlated with standard inflammatory markers and was consistently upregulated across all groups. Additionally, vitamin D treatment appeared to reduce inflammatory marker expression, and age-related changes in inflammatory responses were observed.

These findings suggest that synovial fibroblast molecular profiling could help differentiate between arthritis subtypes and guide early diagnosis, particularly for distinguishing RA from other inflammatory conditions. The potential anti-inflammatory effects of vitamin D and the identification of age-related inflammatory patterns may inform personalized treatment approaches and rehabilitation strategies for different patient phenotypes.

IΚB-Ζ SIGNALING PROMOTES CHONDROCYTE INFLAMMATORY PHENOTYPE, SENESCENCE, AND EROSIVE JOINT PATHOLOGY.

This study investigated how chondrocytes (cartilage cells) develop an inflammatory phenotype that contributes to osteoarthritis progression without requiring massive immune cell infiltration. The researchers used primary chondrocytes from osteoarthritic mice and patients, exposing them to IL-1β and bone matrix particles (found in OA synovial fluid) to examine inflammatory responses, senescence, and the role of IκB-ζ signaling pathways.

Key findings revealed that chondrocytes can autonomously develop a pro-inflammatory phenotype characterized by increased expression of inflammatory markers, RANKL, and senescence-associated secretory phenotype (SASP) genes, all regulated through the NF-κB/IκB-ζ signaling pathway. The study also showed that bone breakdown products in the joint environment, combined with IL-1β, promote oxidative stress and cellular senescence in chondrocytes.

These findings suggest that targeting the IκB-ζ signaling pathway could represent a novel therapeutic approach for osteoarthritis management, and highlight the importance of considering chondrocyte intrinsic inflammation when developing rehabilitation strategies aimed at reducing joint degradation and preserving cartilage function.

SENESCENT CHONDROGENIC PROGENITOR CELLS DERIVED FROM ARTICULAR CARTILAGE OF KNEE OSTEOARTHRITIS PATIENTS CONTRIBUTES TO SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE VIA RELEASE OF IL-6 AND IL-8.

This study investigated why chondrogenic progenitor cells (CPCs) from osteoarthritic knee cartilage fail to repair damaged tissue, comparing cellular aging characteristics between osteoarthritis (OA) patients and healthy controls. Researchers isolated CPCs from cartilage samples and assessed cellular aging markers, oxidative stress levels, inflammatory protein production, and cell morphology using various laboratory techniques including microscopy and genetic analysis. The findings revealed that OA-derived CPCs exhibited significantly higher levels of cellular senescence (premature aging), increased oxidative stress, enlarged cell size with multiple nuclei, and elevated production of inflammatory cytokines IL-6 and IL-8 compared to healthy CPCs. These results suggest that the inflammatory joint environment in osteoarthritis accelerates progenitor cell aging, which may explain poor cartilage repair capacity and indicates that targeting cellular senescence and inflammation could be important therapeutic strategies for physiotherapy and regenerative treatments in knee osteoarthritis management.

FROM CHONDROCYTES TO CHONDRONS, MAINTENANCE OF PHENOTYPE AND MATRIX PRODUCTION IN A COMPOSITE 3D HYDROGEL SCAFFOLD.

This study investigated whether a novel composite hydrogel scaffold (SA-GEL-GA) made from sodium alginate, gelatin, and gum arabic could support cartilage cell growth and matrix production as a potential treatment for osteoarthritis cartilage defects. The researchers cultured bovine articular chondrocytes in the scaffold for 45 days and assessed cell viability, proliferation, morphology, and production of cartilage-specific proteins using various biochemical and imaging techniques. Key findings showed that cells maintained their round, cartilage-like shape while proliferating 6-fold, produced nearly 4-fold more glycosaminoglycans (key cartilage components), and successfully formed chondrons (cells surrounded by protective matrix) with increased collagen II, aggrecan, and CD44 expression. These results suggest the SA-GEL-GA scaffold could offer a more affordable and mechanically tunable alternative to current matrix-assisted chondrocyte transplantation products, potentially improving treatment options for cartilage repair in osteoarthritis patients.

WHEN IS SURGERY PERFORMED? TRENDS, DEMOGRAPHIC ASSOCIATIONS, AND PHENOTYPICAL CHARACTERIZATION OF BASELINE PATIENT-REPORTED OUTCOMES BEFORE TOTAL HIP ARTHROPLASTY.

This study examined trends in patient-reported pain and function scores before total hip arthroplasty (THA) in 6,902 patients from 2016-2020, aiming to understand when patients and surgeons decide to proceed with surgery. **The researchers analyzed Hip Disability and Osteoarthritis Outcome Score (HOOS) data across different demographic groups and used cluster analysis to identify four distinct patient phenotypes based on combinations of pain and function levels.** **Key findings revealed significant health disparities: female, Black, and smoking patients consistently underwent THA with worse baseline pain and function scores, while Black patients showed no improvement in functional thresholds over the 5-year period unlike other groups.** **The identification of four pain-function phenotypes (32.4% had both poor pain and function) suggests that combining these measures provides better preoperative assessment than evaluating them separately, potentially helping physiotherapists and surgeons optimize timing of referrals and tailor perioperative rehabilitation strategies to address specific patient profiles.**

SINGLE-CELL RNA SEQUENCING REVEALS THE CELL TYPES HETEROGENICITY OF HUMAN DISCOID LATERAL MENISCUS CELLS.

This study aimed to identify specific cell types and gene expression patterns in discoid lateral meniscus (DLM) compared to osteoarthritic meniscus to understand why DLM is more injury-prone. The researchers used single-cell RNA sequencing on meniscal tissue samples, followed by pseudo-time analysis and immunohistochemical staining to map cell populations and their spatial distribution. They discovered two novel cell clusters unique to DLM - prehypertrophic chondrocyte 2 (PREHTC-2) and regulatory chondrocyte (REGC-2) populations - primarily located in the white zone of the meniscus, with distinct matrix metalloproteinase (MMP) expression patterns between DLM and osteoarthritic tissue. These findings suggest that DLM has a distinct cellular composition and gene expression profile that may contribute to its increased injury susceptibility, potentially informing targeted therapeutic approaches and helping clinicians better understand the biological basis for the higher failure rates seen with discoid meniscus repairs and rehabilitation.

COMBINATIONS OF PREOPERATIVE PATIENT-REPORTED OUTCOME MEASURE PHENOTYPE (PAIN, FUNCTION, AND MENTAL HEALTH) PREDICT OUTCOME AFTER TOTAL KNEE ARTHROPLASTY.

This study aimed to identify preoperative patient-reported outcome measure (PROM) phenotypes that predict dissatisfaction one year after total knee arthroplasty (TKA). Researchers analyzed 5,274 primary TKA patients, using preoperative scores on knee pain (KOOS-Pain), physical function (KOOS-PS), and mental health (VR-12 MCS) to develop patient phenotypes and predict achievement of Patient Acceptable Symptom State (PASS) at one year.

The study identified that patients with combined low scores across all three domains (pain <41.7, function <51.5, mental health <52.8) had over twice the odds of being dissatisfied at one year, with 16.3% of all patients reporting unacceptable outcomes. These multi-domain phenotypes were stronger predictors of satisfaction than sociodemographic factors and were also associated with longer hospital stays and non-home discharge.

For clinical practice, this suggests that physiotherapists and surgeons should assess pain, function, and mental health together as a combined phenotype rather than individually when counseling TKA candidates. Patients with low scores across multiple domains may benefit from targeted preoperative interventions addressing psychological factors and functional optimization, or alternative treatment pathways before proceeding with surgery.

HIGH GLUCOSE STIMULATING ECM REMODELING AND AN INFLAMMATORY PHENOTYPE IN THE IPFP VIA UPREGULATION OF MFAP5 EXPRESSION.

This study investigated how diabetes contributes to osteoarthritis progression by affecting the infrapatellar fat pad (IPFP), a tissue surrounding the knee joint. Using a diabetic mouse model and cell culture experiments, researchers found that high glucose levels upregulate a protein called MFAP5 in specific progenitor cells within the IPFP, leading to increased tissue scarring (fibrosis) and inflammation. The study identified a distinct inflammatory phenotype in diabetic conditions, where MFAP5 promotes the transformation of progenitor cells into scar-forming cells and increases production of inflammatory markers like IL-6. These findings suggest that diabetic patients may represent a specific osteoarthritis subgroup requiring targeted management approaches, and that MFAP5 could serve as a novel therapeutic target for preventing diabetes-related joint degeneration, potentially informing future physiotherapy strategies for managing osteoarthritis in diabetic populations.

PERSONALIZED RISK MODEL AND LEVERAGING OF MAGNETIC RESONANCE IMAGING-BASED STRUCTURAL PHENOTYPES AND CLINICAL FACTORS TO PREDICT INCIDENCE OF RADIOGRAPHIC OSTEOARTHRITIS.

This study aimed to determine whether MRI-based structural phenotypes could predict the development of radiographic osteoarthritis (OA) over time. Researchers used deep learning to analyze MRI scans from 2,328 participants without radiographic OA at baseline, tracking four structural phenotypes (inflammatory, meniscus/cartilage, subchondral bone, and hypertrophic) over 8 years using the ROAMES classification system.

The study found that three phenotypes significantly increased the risk of developing radiographic OA: inflammatory phenotype increased risk by 3.4 times, subchondral bone phenotype by 1.8 times, and meniscus/cartilage phenotype by 1.6 times. Notably, the hypertrophic phenotype showed sex-specific effects, with women having 2.8 times higher risk compared to men without this phenotype.

These MRI-based phenotypes could enable clinicians to identify high-risk patients earlier and tailor interventions accordingly, potentially allowing physiotherapists to implement targeted preventive strategies before radiographic changes become apparent.

OSTEOARTHRITIS ENDOTYPE DISCOVERY VIA CLUSTERING OF BIOCHEMICAL MARKER DATA.

This study aimed to identify distinct osteoarthritis (OA) subgroups using biochemical markers that reflect joint tissue activity, with the goal of improving patient stratification for personalized treatments. Researchers analyzed baseline biochemical marker data from the IMI-APPROACH cohort using machine learning clustering techniques (k-means algorithm) and explainable AI methods to identify dominant patient subgroups and their driving biological features.

The analysis revealed three distinct OA endotypes with different biological profiles: Cluster 1 characterized by low tissue turnover (minimal repair and cartilage/bone activity), Cluster 2 dominated by structural damage (high bone formation/destruction and cartilage breakdown), and Cluster 3 marked by systemic inflammation (widespread joint tissue breakdown and inflammation). These findings were validated in an independent cohort, with each cluster showing different disease progression patterns - Cluster 1 patients were least likely to progress, Cluster 2 was associated with structural worsening, and Cluster 3 was linked to persistent or worsening pain.

These results support the existence of biologically distinct OA subtypes and suggest that biochemical marker profiling could guide treatment selection and clinical trial design, potentially enabling more targeted physiotherapy and rehabilitation approaches based on each patient's underlying disease mechanisms.

USE OF IMMPACT RECOMMENDATIONS TO EXPLORE PAIN PHENOTYPES IN PEOPLE WITH KNEE OSTEOARTHRITIS.

This study aimed to identify distinct pain phenotypes in knee osteoarthritis patients using standardized IMMPACT recommendations, which include multiple pain domains rather than focusing on single aspects of pain. The researchers used latent profile analysis on 343 participants (mean age 64, 64% female) from Canadian hospitals, analyzing variables such as pain intensity, quality, catastrophizing, sleep, fatigue, anxiety/depression, and sensory testing.

Three distinct pain phenotypes were identified with increasing pain burden from Class 1 to Class 3, differentiated mainly by self-reported measures and temporal summation (pain sensitivity). Classes 2 and 3, characterized by higher pain burden, younger age, female sex, and lower optimism/self-efficacy, showed significantly worse physical function (stair climbing, walking tests), poorer self-reported outcomes, and increased healthcare utilization compared to Class 1.

These findings suggest that using standardized IMMPACT criteria can identify clinically meaningful pain subgroups that differ in functional outcomes and healthcare needs, potentially enabling more targeted physiotherapy and management approaches for knee osteoarthritis patients based on their specific pain phenotype profile.

DISSATISFACTION AFTER TOTAL HIP ARTHROPLASTY ASSOCIATED WITH PREOPERATIVE PATIENT-REPORTED OUTCOME PHENOTYPES.

This study aimed to identify preoperative patient-reported outcome measure (PROM) phenotypes associated with dissatisfaction one year after total hip arthroplasty (THA). Researchers analyzed data from 4,034 THA patients, using preoperative scores on hip pain, physical function, and mental health to create combined phenotypes and determine their association with achieving a "patient acceptable symptom state" (PASS) at one year.

The key finding was that 10.6% of patients remained dissatisfied at one year, with phenotypes characterized by below-average mental health scores being the strongest predictors of dissatisfaction. Patients with the worst combined scores across all three domains (pain, function, and mental health) had double the odds of dissatisfaction and were also more likely to experience non-home discharge and prolonged hospital stays.

These results suggest that assessing pain, physical function, and mental health together as combined phenotypes before surgery can help identify patients at risk for poor outcomes, potentially enabling targeted preoperative interventions or enhanced rehabilitation programs to improve post-surgical satisfaction.

EXPANDING THE CLINICAL SPECTRUM OF COL2A1 RELATED DISORDERS BY A MASS LIKE PHENOTYPE.

This study aimed to identify genetic causes in patients presenting with MASS-like phenotype (tall stature, joint deformities, spinal abnormalities) but testing negative for typical Marfan syndrome mutations. The researchers used gene panel sequencing on four patients from three families who exhibited features including arachnodactyly, spinal deformations, osteoarthritis, and skeletal abnormalities.

The key finding was the identification of likely pathogenic variants in the COL2A1 gene (associated with type II collagenopathies) rather than the expected FBN1 mutations, representing the first reported association between COL2A1 variants and MASS-like phenotype. This discovery expands the recognized clinical spectrum of COL2A1-related disorders beyond the typical skeletal dysplasia, eye, and hearing problems.

For clinical management, this suggests that patients with MASS/Marfan-like features but negative FBN1 testing should undergo COL2A1 gene sequencing, potentially leading to more accurate diagnosis and tailored treatment approaches for their connective tissue disorder and associated osteoarthritis.

KNOCKDOWN OF CIRC-PRKCH ALLEVIATES IL-1Β-TREATED CHONDROCYTE CELL PHENOTYPIC CHANGES THROUGH MODULATING MIR-502-5P/ADAMTS5 AXIS.

This study aimed to investigate how a circular RNA called circ-PRKCH contributes to osteoarthritis (OA) development and cartilage breakdown. Researchers analyzed cartilage samples from 30 OA patients and healthy controls, and used laboratory models where human cartilage cells were treated with inflammatory signals to mimic OA conditions.

The key finding was that circ-PRKCH levels were elevated in OA cartilage and inflammatory conditions, where it disrupts normal cellular function by interfering with protective molecular pathways (specifically the miR-502-5p/ADAMTS5 axis). When researchers reduced circ-PRKCH levels, cartilage cells showed improved survival, growth, and reduced inflammatory damage.

This research identifies a potential molecular subtype of OA characterized by high circ-PRKCH expression and suggests this circular RNA could serve as both a diagnostic marker and therapeutic target. While this is early-stage laboratory research, it may eventually inform personalized treatment approaches for OA patients, though clinical applications for physiotherapy and rehabilitation are not yet established and would require further translational studies.

ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION SURGERY: CREATING A PERMISSIVE HEALING PHENOTYPE IN MILITARY PERSONNEL AND CIVILIANS FOR FASTER RECOVERY.

This study aimed to identify factors contributing to poor outcomes after ACL reconstruction and propose a therapeutic approach to create a "permissive healing environment" for faster recovery in military personnel and civilians. The authors conducted a comprehensive literature review using PubMed, Cochrane, and EMBASE databases, focusing on prevalence, risk factors, and treatment outcomes within the last 10 years. They identified distinct injury phenotypes characterized by early molecular events including joint inflammation, immune dysfunction, and trauma-induced synovial stress, with notable sex-based differences in injury susceptibility and healing responses that remain under-researched. The findings suggest that targeting these early molecular events with upstream therapies (such as adenosine, lidocaine, and magnesium) could reduce complications like arthrofibrosis and post-traumatic osteoarthritis, with important implications for developing personalized rehabilitation protocols that account for sex-specific phenotypes and the systemic nature of ACL injuries.

IDENTIFICATION OF TRANSCRIPTION FACTORS RESPONSIBLE FOR A TRANSFORMING GROWTH FACTOR-Β-DRIVEN HYPERTROPHY-LIKE PHENOTYPE IN HUMAN OSTEOARTHRITIC CHONDROCYTES.

This study aimed to identify the specific transcription factors responsible for TGF-β-driven hypertrophy-like changes in human osteoarthritic chondrocytes. The researchers used luciferase-based assays to measure transcription factor activity and tested specific inhibitors (SB-505124, tofacitinib, and SP-600125) to block different signaling pathways in chondrocytes exposed to TGF-β at concentrations found in OA patients' synovial fluid. They found that TGF-β induces a hypertrophic phenotype characterized by increased expression of key hypertrophy genes, with three transcription factors (SMAD3:4, STAT3, and AP1) showing increased activity, but only the ALK5-SMAD pathway inhibitor effectively blocked this hypertrophic transformation. These findings suggest that targeting the ALK5 kinase pathway could be a specific therapeutic approach for preventing or reversing the harmful hypertrophic changes in cartilage cells that contribute to OA progression, potentially informing future drug development and personalized treatment strategies.

PHENOTYPES IN OSTEOARTHRITIS: WHY DO WE NEED THEM AND WHERE ARE WE AT?

This article aims to provide a comprehensive overview of osteoarthritis phenotyping, examining why phenotype classification is needed and reviewing current progress in the field. The authors present a narrative review covering the conceptual foundations, historical development, and various approaches used to identify distinct OA subgroups. Key findings highlight that OA phenotyping research has evolved from simple clinical classifications to more sophisticated approaches incorporating biomechanical, biochemical, and molecular data to identify meaningful patient subgroups. The implications suggest that better phenotype identification could lead to more personalized treatment approaches in osteoarthritis management, potentially improving outcomes for both clinical practice and rehabilitation strategies, though the field is still developing toward practical clinical applications.

PROSPECTS OF DISEASE-MODIFYING OSTEOARTHRITIS DRUGS.

This review examined the current pipeline of disease-modifying osteoarthritis drugs (DMOADs) in phase 2/3 clinical trials, addressing the critical unmet need for treatments that can alter disease progression in a condition affecting nearly 23% of the global population. The authors organized DMOAD candidates according to three distinct osteoarthritis endotypes based on underlying pathogenic mechanisms: inflammation-driven, bone-driven, and cartilage-driven phenotypes. The review identified promising therapeutic targets within each endotype but highlighted significant challenges in drug development using the PICO framework (Population, Interventions, Comparison, Outcomes). The findings suggest that successful DMOAD development may require a precision medicine approach that matches specific treatments to patient phenotypes, which could fundamentally change osteoarthritis management by moving beyond symptom control to actual disease modification.

CALCIUM-BINDING PROTEIN 39 OVEREXPRESSION PROMOTES MACROPHAGES FROM 'M1' INTO 'M2' PHENOTYPE AND IMPROVES CHONDROCYTE DAMAGE IN OSTEOARTHRITIS BY ACTIVATING THE AMP-ACTIVATED PROTEIN KINASE/SIRTUIN 1 AXIS.

This study investigated whether calcium-binding protein 39 (CAB39) could protect against osteoarthritis by influencing immune cell behavior and cartilage damage. Researchers used cell culture models of cartilage cells and immune cells (macrophages), along with a mouse model of osteoarthritis, to test the effects of increasing or decreasing CAB39 levels through genetic manipulation.

The key finding was that CAB39 promotes a beneficial shift in macrophage behavior - from the inflammatory 'M1' type that damages cartilage to the anti-inflammatory 'M2' type that helps healing - while also protecting cartilage cells from death and damage. This protective effect works through activation of a specific cellular pathway (AMPK/SIRT-1) that regulates metabolism and inflammation.

These results suggest that targeting CAB39 or its associated pathways could represent a new therapeutic approach for osteoarthritis management, potentially through treatments that promote anti-inflammatory immune responses and cartilage protection, though translation to clinical physiotherapy applications would require further research in human studies.

COMPARISON OF CLINICALLY RELEVANT ADIPOSE PREPARATIONS ON ARTICULAR CHONDROCYTE PHENOTYPE IN A NOVEL IN VITRO CO-CULTURE MODEL.

This study aimed to determine which adipose tissue preparation method produces the best therapeutic effects for osteoarthritis treatment by comparing their impact on cartilage cell behavior. Researchers co-cultured human knee cartilage cells (chondrocytes) with three different adipose preparations: stromal vascular fraction (SVF) from enzymatic digestion, mechanically emulsified nanofat, and bead-mill processed Lipogems, then measured gene expression related to inflammation and cartilage metabolism at 36 and 72 hours.

The key finding was that different processing methods created distinct chondrocyte responses - SVF increased harmful inflammatory and cartilage-degrading activity, while both mechanical processing methods (nanofat and Lipogems) reduced inflammation and promoted beneficial cartilage matrix production. Notably, nanofat showed temporary cartilage-building effects, whereas Lipogems consistently enhanced cartilage synthesis at both time points.

These results suggest that mechanical processing of adipose tissue may be more effective than isolated cell preparations for osteoarthritis treatment, providing important guidance for clinicians considering adipose-based therapies and highlighting the need to optimize processing methods in regenerative approaches to joint degeneration.

A NOVEL APPROACH TO STUDYING EARLY KNEE OSTEOARTHRITIS ILLUSTRATES THAT BILATERAL MEDIAL TIBIOFEMORAL OSTEOARTHRITIS IS A HERITABLE PHENOTYPE: AN OFFSPRING STUDY.

This study aimed to investigate the heritability of knee osteoarthritis by examining offspring of people with and without bilateral medial tibiofemoral osteoarthritis from the Osteoarthritis Initiative. The researchers recruited 188 offspring (mean age 43 years) from two parent groups - those with bilateral radiographic medial tibiofemoral OA and those without any tibiofemoral OA - and assessed them through surveys, X-rays, and MRI scans of 20 offspring (10 from each group).

The key finding was that offspring of parents with bilateral medial tibiofemoral OA showed significantly higher rates of radiographic tibiofemoral OA (16/18 knees vs 2/20 knees) and meniscal abnormalities compared to offspring of unaffected parents, supporting the heritability of this specific OA phenotype. These results suggest that bilateral medial tibiofemoral osteoarthritis represents a distinct, heritable subtype of knee OA, which could inform early identification strategies and targeted prevention approaches in clinical practice, particularly for individuals with strong family histories of this specific pattern of knee arthritis.

[ANALYSIS OF REINJECTION PERIODICITY IN KNEE OSTEOARTHRITIS WITH DIFFERENT TYPES OF HYALURONIC ACIDS].

**Study Summary:**

This retrospective study aimed to evaluate how long different types of hyaluronic acid (HA) injections provide benefit in knee osteoarthritis patients before requiring repeat treatment, and whether osteoarthritis severity affects reinjection timing. The researchers analyzed 110 HA injections in 67 patients (average age 72 years, 85% women) treated between 2017-2019, examining four different HA formulations with varying molecular weights and tracking time until reinjection was needed. While 28% of patients required reinjection, the study found no statistically significant differences between HA types or osteoarthritis severity levels in determining reinjection intervals, though one formulation (HA3 - 2% concentration, 1.2 million Dalton molecular weight) showed a numerically longer duration between injections (9.3 months vs. 5-12.5 months for others). These findings suggest that patient response to HA injections may be more individualized than previously thought, indicating that physiotherapists and clinicians should consider patient-specific factors rather than relying solely on HA type or radiographic severity when planning treatment intervals.

GAIT BIOMECHANICS PHENOTYPES AMONG TOTAL KNEE ARTHROPLASTY CANDIDATES BY MACHINE LEARNING CLUSTER ANALYSIS.

This study aimed to identify distinct biomechanical phenotypes among total knee arthroplasty (TKA) candidates using gait analysis data and machine learning, then track how these groups responded to surgery. Researchers analyzed 3D gait patterns in 134 patients before TKA and 105 patients one year after surgery, using principal component analysis and hierarchical clustering based on demographics and knee mechanics during walking.

Four distinct patient phenotypes emerged, primarily distinguished by sex and baseline knee function - two "higher functioning" clusters (mostly male) and two "lower functioning" clusters (mostly female). The higher functioning groups showed more dynamic knee loading patterns before surgery, including greater sagittal flexion moments and frontal plane adduction moments during walking.

Importantly, the lower functioning clusters experienced significantly greater improvements in knee mechanics after TKA surgery, while higher functioning patients showed less biomechanical change post-operatively. This phenotype-based approach could help clinicians better predict surgical outcomes and develop targeted rehabilitation strategies that address the specific functional needs of different patient subgroups.

HUMAN INTEGRIN Α10Β1-SELECTED MESENCHYMAL STEM CELLS HOME TO CARTILAGE DEFECTS IN THE RABBIT KNEE AND ASSUME A CHONDROCYTE-LIKE PHENOTYPE.

This study investigated whether specially selected human mesenchymal stem cells (MSCs) could effectively target and repair cartilage damage when injected into joints. The researchers used MSCs selected for integrin α10β1 expression, labeled them with trackable nanoparticles, and injected them into rabbit knees with created cartilage defects, then monitored their movement and behavior using MRI and microscopy over 10 days.

The key finding was that these integrin α10β1-selected MSCs successfully migrated to and concentrated within the cartilage defects, with peak accumulation occurring 1-4 days after injection. Importantly, the MSCs transformed into chondrocyte-like cells and began producing cartilage-specific proteins (aggrecan and collagen type II) throughout all layers of the repair tissue.

These results suggest that using specifically selected MSC phenotypes based on integrin α10β1 expression could enhance targeted cartilage repair therapies. For clinical management, this approach may offer a more effective cell-based treatment for cartilage defects and osteoarthritis by ensuring injected cells actually reach damaged areas and contribute meaningfully to tissue regeneration rather than being lost elsewhere in the joint.

BICLUSTERING REVEALS POTENTIAL KNEE OA PHENOTYPES IN EXPLORATORY ANALYSES: DATA FROM THE OSTEOARTHRITIS INITIATIVE.

This study aimed to identify distinct knee osteoarthritis (KOA) phenotypes using biclustering, a data analysis method that simultaneously groups patients and clinical features to reveal meaningful subgroups. The researchers analyzed baseline data from 6,461 knees in the Osteoarthritis Initiative, applying biclustering to 86 clinical features and tracking outcomes over 96 months including radiographic progression, knee replacement surgery, and pain scores.

The analysis identified six distinct biclusters (phenotypes): one with better prognosis (#1), three with similar outcomes to the overall cohort (#2, 3, 6), and two with poorer prognosis (#4, 5). Interestingly, the high-risk phenotypes (#4, 5) showed more structural deterioration and higher rates of knee replacement but paradoxically experienced improvements in pain scores over time, while the low-risk phenotype (#1) had stable pain but less structural progression.

These findings suggest that KOA patients can be stratified into meaningful subgroups with different risk profiles, which could inform personalized treatment approaches and help physiotherapists tailor interventions based on predicted outcomes rather than treating all patients uniformly.

REPURPOSED AND INVESTIGATIONAL DISEASE-MODIFYING DRUGS IN OSTEOARTHRITIS (DMOADS).

This narrative review aimed to examine disease-modifying osteoarthritis drugs (DMOADs) that have advanced to Phase II and III clinical trials, organized by underlying disease mechanisms. The authors categorized potential treatments according to three main osteoarthritis endotypes: bone-driven, synovitis-driven, and cartilage-driven pathways, reviewing both repurposed existing medications and novel investigational agents. Despite extensive research investment, no DMOADs have achieved regulatory approval yet, though the review identified promising findings from post-hoc analyses of failed trials and highlighted lessons learned from these setbacks. The endotype-based approach suggests that future osteoarthritis management may need to move toward personalized treatment strategies targeting specific disease mechanisms, potentially informing physiotherapists and clinicians about which patients might benefit most from particular interventions based on their dominant pathological processes.

CHARACTERIZATION AND IN VITRO CYTOTOXICITY SAFETY SCREENING OF FRACTIONATED ORGANOSOLV LIGNIN ON DIVERSE PRIMARY HUMAN CELL TYPES COMMONLY USED IN TISSUE ENGINEERING.

This study investigated the safety and biocompatibility of fractionated organosolv lignin, a plant-derived biopolymer, for potential use in tissue engineering applications relevant to musculoskeletal repair. The researchers characterized different molecular weight fractions of lignin and tested their cytotoxic effects on various primary human cell types including mesenchymal stem cells, osteoblasts, chondrocytes, and fibroblasts using cell viability assays over multiple time points.

The key finding was that low molecular weight lignin (2543 g/mol) demonstrated excellent biocompatibility, maintaining 70-100% cell viability across different cell types at specific concentrations: 0.02 mg/ml for stem cells and osteoblasts, 0.02-0.04 mg/ml for gingival cells, and 0.02-0.08 mg/ml for ligament fibroblasts and chondrocytes, though higher concentrations proved cytotoxic. Notably, when incorporated into agarose hydrogels, low molecular weight lignin enhanced chondrocyte attachment and created mechanical properties (3-11 kPa stiffness) similar to natural cartilage matrix.

These findings suggest that appropriately processed lignin could serve as a promising, biocompatible biomaterial for developing scaffolds and therapeutic interventions in cart

CLINICAL RESULTS AFTER DESIGN MODIFICATION OF LOSPA TOTAL KNEE ARTHROPLASTY SYSTEM: COMPARISON BETWEEN POSTERIOR-STABILIZED (PS) AND PS PLUS TYPES.

This study aimed to compare clinical outcomes between two versions of the LOSPA total knee arthroplasty system - the original posterior-stabilized (PS) type and the modified PS Plus type, which features design changes to improve stability and reduce patella-post impingement. The researchers conducted a retrospective analysis of 558 knees in 342 patients, comparing clinical outcomes (range of motion, WOMAC scores, Knee Society Scores) and radiographic results between the PS group (212 cases) and PS Plus group (346 cases) at 2-year follow-up. Both implant types demonstrated significant clinical improvements with no meaningful differences between groups - KSS improved from around 53 to 92-93 points and WOMAC scores improved from around 51 to 15 points, with similar complication rates and over 98% survival rates. These findings suggest that while the PS Plus design modifications were intended to address specific biomechanical issues, both implant phenotypes provide equivalent short-term clinical outcomes, indicating that factors beyond implant design may be more important determinants of early TKA success in rehabilitation and management planning.

BIODEGRADABLE HOLLOW-STRUCTURED NANOZYMES MODULATE PHENOTYPIC POLARIZATION OF MACROPHAGES AND RELIEVE HYPOXIA FOR TREATMENT OF OSTEOARTHRITIS.

This study aimed to develop and test biodegradable hollow-structured manganese Prussian blue nanozymes (HMPBzyme) as a novel treatment for osteoarthritis by targeting the inflammatory joint microenvironment. The researchers used a biomineralization strategy to create pH-responsive nanozymes and tested them in both laboratory cell cultures and rat models of osteoarthritis, examining their effects on inflammation, oxygen levels, and cartilage health.

The key finding was that HMPBzyme successfully shifted macrophage phenotypes from pro-inflammatory M1 to anti-inflammatory M2 subtypes while simultaneously reducing harmful reactive oxygen species and relieving tissue hypoxia. This dual mechanism led to reduced cartilage degeneration and improved joint health in the osteoarthritis models.

For clinical management, this research suggests that targeting macrophage phenotypic switching could be a promising therapeutic strategy for osteoarthritis treatment, potentially complementing current physiotherapy approaches by addressing the underlying inflammatory processes that drive joint deterioration.

EXTRACELLULAR VESICLES ENRICHED IN CONNEXIN 43 PROMOTE A SENESCENT PHENOTYPE IN BONE AND SYNOVIAL CELLS CONTRIBUTING TO OSTEOARTHRITIS PROGRESSION.

This study investigated how cellular aging (senescence) spreads throughout joints in osteoarthritis, specifically examining the role of small extracellular vesicles containing connexin 43 protein (CX43-SEVs) released by cartilage cells. Researchers analyzed these vesicles from human osteoarthritic cartilage and tested their effects on various joint tissues including cartilage, synovium, and bone cells using laboratory cell culture methods.

The key finding was that CX43-enriched vesicles act as "messengers" that spread cellular aging and inflammation throughout the joint by inducing a senescent phenotype in healthy cells, triggering the release of inflammatory molecules (IL-1β, IL-6, MMPs) and activating cellular reprogramming pathways. This mechanism explains how osteoarthritis progresses from cartilage breakdown to affect the entire joint structure, and potentially how the disease may spread between joints.

These findings suggest that CX43-positive vesicles could serve as new biomarkers for tracking osteoarthritis progression and represent novel therapeutic targets, potentially informing future physiotherapy approaches that consider the whole-joint inflammatory environment rather than focusing solely on mechanical factors.

HUMAN FETAL CARTILAGE-DERIVED PROGENITOR CELLS EXHIBIT ANTI-INFLAMMATORY EFFECT ON IL-1Β-MEDIATED OSTEOARTHRITIS PHENOTYPES IN VITRO.

This study investigated whether human fetal cartilage-derived progenitor cells (HFCPCs) could reduce inflammation and improve osteoarthritis (OA) characteristics in laboratory conditions. Researchers tested different priming factors on HFCPCs and then co-cultured the optimally-primed cells with human chondrocytes and synovial cells that had been treated with IL-1β to mimic OA inflammation.

The key finding was that HFCPCs primed with poly(I:C) effectively reduced inflammatory markers (IL-6, IL-1β, and matrix-degrading enzymes) in synovial cells while simultaneously increasing healthy cartilage components (aggrecan and collagen type II) in chondrocytes. This suggests that primed HFCPCs can address both the inflammatory and cartilage degradation aspects that characterize different OA phenotypes.

These results indicate that cell-based therapies using primed fetal cartilage progenitor cells could potentially target multiple pathways involved in OA progression, offering a promising approach for future regenerative treatments that go beyond current symptom management strategies in physiotherapy and rehabilitation.

PHENOTYPE DIVERSITY OF MACROPHAGES IN OSTEOARTHRITIS: IMPLICATIONS FOR DEVELOPMENT OF MACROPHAGE MODULATING THERAPIES.

This review examines the diverse roles of macrophages in osteoarthritis to inform the development of targeted therapeutic approaches. The authors analyzed existing literature on macrophage phenotypes, their functions in OA joints, and their interactions with surrounding tissues. Key findings reveal that macrophages exist in heterogeneous populations that can both promote disease progression (through inflammation, pain, and cartilage destruction) and support tissue repair, explaining why simply reducing macrophage numbers may be harmful in OA models. These insights suggest that future OA treatments and rehabilitation strategies should focus on modulating specific macrophage phenotypes rather than broadly suppressing macrophage activity, potentially offering more precise therapeutic targets for managing the inflammatory component of osteoarthritis.

ENDOPLASMIC RETICULUM STRESS TRIGGERED AUTOPHAGY AND REGULATED THE PHENOTYPE TRANSFORMATION OF RHEUMATOID ARTHRITIS SYNOVIAL FIBROBLASTS VIA THE IRE1/JNK PATHWAY.

This study investigated how endoplasmic reticulum (ER) stress triggers cellular changes in rheumatoid arthritis (RA) synovial fibroblasts that contribute to joint inflammation and damage. Researchers compared synovial tissue from RA and osteoarthritis patients using molecular techniques, and tested how blocking specific pathways affected cell behavior in laboratory experiments. The key finding was that RA synovial fibroblasts undergo a harmful "phenotype transformation" - becoming more aggressive with increased proliferation and invasion capabilities - through an ER stress-autophagy pathway involving IRE1/JNK signaling, with this process being significantly more active in RA compared to osteoarthritis tissue. These results suggest that targeting the ER stress-autophagy pathway, particularly the IRE1/JNK components, could offer new therapeutic approaches for managing RA synovitis and potentially reducing joint destruction, though this research focuses on cellular mechanisms rather than direct physiotherapy applications.

BIOMARKER CLUSTERS DIFFERENTIATE PHENOTYPES OF LUMBAR SPINE DEGENERATION AND LOW BACK PAIN: THE JOHNSTON COUNTY OSTEOARTHRITIS PROJECT.

This study aimed to identify distinct biomarker-based phenotypes of lumbar spine degeneration and determine their association with low back pain (LBP) using data from 731 participants in the Johnston County Osteoarthritis Project. Researchers measured 11 serum and urinary biomarkers and used cluster analysis to group participants, then examined associations with radiographic spine changes and pain symptoms.

Three distinct phenotypes emerged: a referent group with low biomarker levels and minimal structural changes, a "structural degeneration" group characterized by disc narrowing and facet joint changes without significant pain, and a "structural degeneration + inflammation + pain" group associated with vertebral osteophytes, facet joint changes, and symptomatic LBP. The structural-only phenotype was associated with radiographic changes but less likely to have pain, while the inflammatory phenotype showed strong associations with both structural changes and clinical symptoms.

These biomarker-defined phenotypes could help clinicians identify patients who may benefit from different treatment approaches—targeting structural preservation in asymptomatic degenerative cases versus anti-inflammatory interventions for those with the pain-associated inflammatory phenotype, potentially improving personalized management strategies for lumbar spine conditions.

MECHANICALLY ALIGNED TOTAL KNEE ARTHROPLASTY WITH THE EXTENSION-FIRST TECHNIQUE DOES NOT EQUALLY RESTORE NEUTRAL KNEE ALIGNMENT IN ALL PREOPERATIVE KNEE PHENOTYPES.

This study investigated whether mechanically aligned total knee arthroplasty using the extension-first technique equally restores neutral knee alignment across different preoperative knee phenotypes. The researchers analyzed pre- and postoperative whole-leg radiographs from 112 patients, categorizing them into varus, neutral, or valgus phenotypes based on hip-knee-ankle angles and examining changes in leg alignment after surgery. The key finding was that preoperative knee phenotype significantly influenced postoperative alignment outcomes: patients with preoperative varus alignment were more likely to achieve neutral alignment (46%) compared to those with valgus alignment (39%), while a substantial proportion of patients retained their original phenotype (43% of varus remained varus, 58% of valgus remained valgus). These results suggest that the extension-first mechanically aligned technique does not uniformly restore neutral alignment across all knee phenotypes, particularly struggling with valgus knees, which has important implications for surgical planning and supports personalized alignment strategies in total knee arthroplasty.

POTENTIAL METHODS OF TARGETING CELLULAR AGING HALLMARKS TO REVERSE OSTEOARTHRITIC PHENOTYPE OF CHONDROCYTES.

This review aimed to explore the connection between cellular aging processes and osteoarthritis (OA) development, specifically examining how chondrocytes (cartilage cells) change during OA progression. The authors analyzed existing literature to compare cellular changes in OA chondrocytes with established hallmarks of cellular aging, then proposed potential therapeutic methods based on anti-aging research from other diseases and cell types. The key finding was that OA chondrocytes exhibit many similar alterations to aged cells, suggesting that cellular aging mechanisms may drive the osteoarthritic phenotype in cartilage cells. These insights could lead to novel disease-modifying treatments for OA that target aging processes, potentially offering new therapeutic avenues beyond current symptom management approaches used in physiotherapy and clinical practice.

PHENOTYPE-GENOTYPE ANALYSIS OF CAUCASIAN PATIENTS WITH HIGH RISK OF OSTEOARTHRITIS.

This study aimed to identify genetic variants and phenotypic relationships in osteoarthritis (OA) by examining sex-specific genetic associations and comorbidities using genome-wide association study (GWAS) methods. The researchers analyzed data from 3,366 OA patients in the Osteoarthritis Initiative, conducting sex-specific GWAS including X-chromosome analysis and using Mendelian randomization to explore causal relationships between OA and related clinical features.

The study identified one significant OA-associated genetic locus (rs2305570) through sex-specific analysis and found strong genetic correlations between knee OA and inflammatory diseases (eczema, multiple sclerosis, Crohn's disease), as well as positive correlations with heart disease and stroke. Importantly, knee malalignment emerged as a major causal risk factor for OA development, while surprisingly, knee pain was not found to be causative despite being the most common OA symptom.

These findings suggest OA phenotyping should consider sex-specific genetic factors (particularly X-chromosome variants in women) and inflammatory comorbidities, with implications for physiotherapy focusing on biomechanical interventions targeting knee alignment rather than solely symptom-based approaches.

KNEE OSTEOARTHRITIS PHENOTYPES BASED ON SYNOVIAL FLUID IMMUNE CELLS CORRELATE WITH CLINICAL OUTCOME TRAJECTORIES.

This study aimed to identify knee osteoarthritis patient subgroups based on immune cell patterns in synovial fluid and determine how these relate to clinical outcomes over 3-6 months. Researchers used flow cytometry to analyze synovial fluid immune cells from 119 knee osteoarthritis patients and applied network analysis to identify distinct immune phenotypes, which were then correlated with symptom trajectories.

Four distinct immune phenotypes were identified: an 'activated' phenotype (70% of patients improved), a 'lymphoid progressive' phenotype (associated with lower pain levels), a 'myeloid progressive' phenotype, and an 'aggressive' phenotype (only 39% improved). The phenotypes differed in their composition of T-lymphocytes, macrophages, neutrophils, and NK cells, as well as their activation levels.

These findings suggest that synovial fluid immune profiling could help predict which knee osteoarthritis patients are likely to improve naturally versus those with more resistant, inflammatory disease patterns. This immune-based phenotyping approach may eventually guide personalized treatment decisions, potentially helping clinicians identify patients who might benefit from anti-inflammatory interventions versus those likely to respond well to standard physiotherapy and conservative management.

DIRECT COMPARISON OF NON-OSTEOARTHRITIC AND OSTEOARTHRITIC SYNOVIAL FLUID-INDUCED INTRACELLULAR CHONDROCYTE SIGNALING AND PHENOTYPE CHANGES.

This study aimed to directly compare how synovial fluid from healthy versus end-stage osteoarthritic knees affects chondrocyte (cartilage cell) behavior and identify the underlying molecular mechanisms. The researchers used protein profiling, cell signaling arrays, and gene expression analysis to examine chondrocyte responses to different synovial fluid types, and tested tissue samples from cartilage, synovium, fat pad, and meniscus to determine the sources of inflammatory signals.

The key finding was that osteoarthritic synovial fluid contains elevated levels of inflammatory molecules (cytokines, chemokines, growth factors) that activate specific cellular pathways (MAPK, AKT, NFκB) in chondrocytes. These distinct signaling patterns led to harmful changes in cartilage cells, including loss of normal cartilage characteristics, increased fibrosis, enhanced inflammation, production of cartilage-degrading enzymes, and abnormal cell proliferation.

This research provides the first mechanistic comparison showing how the joint environment in osteoarthritis directly damages cartilage cells through specific molecular pathways. For clinicians and physiotherapists, these findings suggest that targeting the inflammatory joint environment and these specific signaling pathways could be important therapeutic strategies, potentially informing the development of treatments that address the underlying biological processes rather than just symptoms.

FGF RECEPTOR INHIBITOR BGJ398 PARTIALLY RESCUES OSTEOARTHRITIS-LIKE PHENOTYPE IN OLDER HIGH MOLECULAR WEIGHT FGF2 TRANSGENIC MICE VIA MULTIPLE MECHANISMS.

This study investigated whether the drug BGJ398 (an FGF receptor inhibitor) could reverse osteoarthritis-like changes in genetically modified mice that model X-linked hypophosphatemia (XLH)-related degenerative osteoarthritis. Researchers treated 8-month-old female transgenic mice with BGJ398 for six weeks and used micro-CT, histology, and molecular analyses to examine knee joint changes and underlying signaling pathways.

BGJ398 treatment successfully reversed osteoarthritis changes in both cartilage and subchondral bone by blocking multiple harmful molecular pathways, including reduced expression of cartilage-degrading enzymes (MMP13 and ADAMTS5) and normalization of bone signaling pathways. These findings suggest that FGF receptor inhibitors like BGJ398 could potentially serve as targeted therapies for osteoarthritis in patients with XLH, offering a mechanism-based treatment approach that addresses both cartilage degradation and abnormal bone remodeling in this specific osteoarthritis phenotype.

STRUCTURAL PHENOTYPES OF KNEE OSTEOARTHRITIS: POTENTIAL CLINICAL AND RESEARCH RELEVANCE.

This review examines the concept of structural phenotypes in knee osteoarthritis to understand disease heterogeneity and improve treatment targeting. The authors describe five proposed structural phenotypes based on imaging features: inflammatory (marked synovitis/effusion), meniscus-cartilage (severe meniscal and cartilage damage), subchondral bone (large bone marrow lesions), hypertrophic (large osteophytes with cartilage damage), and atrophic (absent osteophytes with cartilage damage). The key finding is that these phenotypes represent distinct structural patterns of joint damage, though they are not mutually exclusive and patients may present with multiple phenotypes simultaneously. For clinical practice, this phenotyping approach could enable more personalized treatment strategies and help identify joints at risk for progression, though the authors acknowledge the concept is still developing and requires further validation before widespread clinical implementation.

ASSOCIATION OF MU OPIOID RECEPTOR (A118G) AND BDNF (G196A) POLYMORPHISMS WITH REHABILITATION-INDUCED CORTICAL INHIBITION AND ANALGESIC RESPONSE IN CHRONIC OSTEOARTHRITIS PAIN.

This study investigated whether specific genetic variations could predict treatment responses in knee osteoarthritis patients by examining OPRM1 and BDNF gene polymorphisms alongside brain cortical activity measures. Researchers analyzed 113 chronic knee OA patients using genetic testing, transcranial magnetic stimulation to assess motor cortex excitability, and clinical outcomes following rehabilitation treatment. Key findings revealed that patients carrying OPRM1 (A118G) or BDNF (G196A) genetic variants were significantly less likely to experience pain improvement after rehabilitation (85% and 72% reduced odds respectively), while OPRM1 carriers also showed poorer improvements in cortical inhibition measures. These genetic markers appear to identify distinct phenotypic subgroups that respond differently to rehabilitation, suggesting potential for personalized treatment approaches where genetic testing could help physiotherapists and clinicians predict which OA patients are most likely to benefit from standard rehabilitation protocols.

PHENOTYPIC AND FUNCTIONAL CHARACTERISATION OF SYNOVIAL FLUID-DERIVED NEUTROPHILS IN KNEE OSTEOARTHRITIS AND KNEE INFECTION.

This study aimed to characterize neutrophils in synovial fluid from knee osteoarthritis (KOA) patients compared to knee infections, and identify distinct KOA phenotypes based on neutrophil abundance. Researchers analyzed neutrophil surface markers, inflammatory mediators, and functional properties in synovial fluid samples, then subdivided KOA patients into high (10-60%) versus low (<10%) neutrophil groups.

The findings revealed that KOA patients with high synovial fluid neutrophils represent a distinct inflammatory phenotype, characterized by elevated levels of key inflammatory proteins (TNF-α, IL-1RA, MMP-9) and different neutrophil surface marker expression patterns that persist over time. Importantly, KOA neutrophils showed different functional characteristics compared to infection-related neutrophils, including increased reactive oxygen species production and phagocytic activity.

These results suggest that neutrophil-driven inflammation may define a specific KOA subgroup with potentially different disease mechanisms and treatment responses, highlighting the need for personalized management approaches that consider inflammatory phenotyping in osteoarthritis care.

SAFETY AND EFFICACY OF PROBIOTIC SUPPLEMENTATION IN 8 TYPES OF INFLAMMATORY ARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF 34 RANDOMIZED CONTROLLED TRIALS.

This systematic review and meta-analysis aimed to evaluate the safety and efficacy of probiotic supplementation across eight types of inflammatory arthritis conditions. The researchers conducted a comprehensive search of multiple databases through May 2022, identifying 34 randomized controlled trials involving various inflammatory conditions including rheumatoid arthritis, osteoarthritis, psoriasis, spondyloarthritis, and others. The findings revealed condition-specific benefits: probiotics reduced inflammatory markers (CRP) in rheumatoid arthritis, improved bone mineral density in osteoporosis, lowered uric acid levels in gout, and generally improved symptoms across osteoarthritis, juvenile idiopathic arthritis, and spondyloarthritis, with no increase in adverse events reported. These results suggest that probiotic supplementation could serve as a safe adjunctive treatment approach for various inflammatory arthritis conditions, though the authors emphasize that more high-quality trials are needed to establish optimal dosing protocols and confirm efficacy before routine clinical implementation.

COMORBIDITY PHENOTYPES AND RISK OF MORTALITY IN PATIENTS WITH OSTEOARTHRITIS IN THE UK: A LATENT CLASS ANALYSIS.

This UK study aimed to identify comorbidity patterns in osteoarthritis (OA) patients and examine their relationship with medication use and mortality risk. Researchers used latent class analysis to analyze 30 different health conditions in over 418,000 newly diagnosed OA patients compared to 243,000 matched controls without OA from a large medical database (2000-2019).

The analysis revealed six distinct comorbidity clusters, with high-risk clusters characterized by combinations of high blood pressure, heart/circulation problems, and metabolic diseases. Notably, a cluster that also included chronic kidney disease was associated with particularly high mortality risk in hand OA patients (2.5 times higher) compared to hip/knee OA patients (1.3 times higher).

The findings showed that opioid use within the first year significantly increased mortality risk across all groups, while anti-inflammatory drugs (NSAIDs) showed no such association. These results suggest that clinicians and physiotherapists should consider specific comorbidity patterns when managing OA patients, particularly being cautious with opioid prescribing and potentially emphasizing non-pharmacological interventions for high-risk phenotypes.

IDENTIFICATION OF SYMPTOM PHENOTYPES OF HAND OSTEOARTHRITIS USING HIERARCHICAL CLUSTERING: RESULTS FROM THE DIGICOD COHORT.

This study aimed to identify distinct symptom-based phenotypes in hand osteoarthritis (HOA) using cardinal symptoms of pain, functional limitation, stiffness, and aesthetic discomfort. Researchers used hierarchical clustering analysis on data from 389 patients in the DIGICOD cohort, analyzing AUSCAN subscores and aesthetic discomfort ratings to identify subgroups.

Five distinct clusters were identified: two with low-to-mild symptoms (clusters 1-2), one with isolated aesthetic concerns (cluster 3), one with high pain/stiffness/functional limitation but low aesthetic discomfort (cluster 4), and one combining severe symptoms across all domains (cluster 5). Notably, aesthetic discomfort was linked to more severe structural disease (erosive HOA and joint nodes), while only one-third of patients had high pain scores, and patient expectations varied significantly between clusters.

These findings suggest HOA comprises distinct symptom-based subtypes that may require different management approaches, potentially enabling more personalized physiotherapy and treatment strategies based on each patient's specific symptom profile and expectations.

RISK ESTIMATION OF DEGENERATIVE JOINT DISEASE IN TEMPOROMANDIBULAR DISORDER PATIENTS WITH DIFFERENT TYPES OF SAGITTAL AND CORONAL DISC DISPLACEMENTS: MRI AND CBCT ANALYSIS.

This study investigated the relationship between different types of temporomandibular joint disc displacement patterns and degenerative joint disease (DJD) risk in 301 TMD patients using MRI and CBCT imaging. Researchers classified disc displacements into eight distinct phenotypes based on sagittal and coronal planes, including anterior displacement with/without reduction, sideways displacement, posterior displacement, and combinations thereof.

The key finding was that anterior disc displacement phenotypes showed dramatically increased DJD risk compared to normal joints, with anterior displacement without reduction showing the highest odds ratio (30x increased risk), followed by anterior displacement with reduction (2.4x risk). Importantly, isolated sideways or posterior displacements showed no significant association with degenerative changes.

These findings suggest that TMD patients should be phenotyped based on specific displacement patterns, as anterior displacement (particularly without reduction) identifies a high-risk subgroup requiring more aggressive monitoring and potentially earlier intervention to prevent or manage progressive joint degeneration.

THE INFLAMMA-TYPE: A PATIENT PHENOTYPE CHARACTERIZED BY A DYSREGULATED INFLAMMATORY RESPONSE AFTER LOWER EXTREMITY ARTICULAR FRACTURE.

This study aimed to identify distinct patient phenotypes based on inflammatory biomarkers in synovial fluid following lower extremity articular fractures. The researchers analyzed synovial fluid from 113 patients with tibial plateau, tibial plafond, or rotational ankle fractures, measuring concentrations of inflammatory cytokines (IL-1β, IL-1RA, IL-6, IL-8, IL-10) and matrix metalloproteinases (MMP-1, -3, -13) using cluster analysis. The analysis revealed an "inflamma-type" phenotype characterized by a dysregulated inflammatory response with elevated pro-inflammatory cytokines and degradative enzymes that are known to contribute to post-traumatic osteoarthritis development. This phenotyping approach could help clinicians identify high-risk patients who may benefit from targeted anti-inflammatory interventions or more intensive rehabilitation strategies to prevent or slow post-traumatic osteoarthritis progression.

THE IMPACT OF DIFFERENT ALIGNMENT STRATEGIES ON BONE CUTS FOR NEUTRAL KNEE PHENOTYPES IN TOTAL KNEE ARTHROPLASTY.

This study aimed to determine which total knee arthroplasty (TKA) alignment strategy requires the least bone resection and soft tissue disruption for different neutral knee phenotypes. The researchers simulated four alignment approaches (mechanical, anatomical, restricted kinematic, and unrestricted kinematic) on four common neutral knee phenotypes using weight-bearing X-rays, measuring the required bone cuts in millimeters.

The findings revealed significant variation in bone resection requirements depending on the phenotype-alignment strategy combination. For the most common neutral phenotype (30% prevalence), bone cuts remained minimal (<4mm) regardless of alignment strategy, but other neutral phenotypes required substantial bone resection—up to 6mm medial tibial elevation and 9mm lateral femoral adjustment with mechanical alignment in one phenotype.

The study demonstrates that even within "neutral" knee phenotypes, the choice of alignment strategy can dramatically impact surgical invasiveness, with strategies requiring minimal joint line obliquity changes being preferable. These findings suggest that personalized alignment strategies based on individual knee phenotypes could optimize TKA outcomes by minimizing soft tissue disruption while maintaining proper component positioning.

ANIMAL MODELS OF OSTEOARTHRITIS PART 1-PRECLINICAL SMALL ANIMAL MODELS: CHALLENGES AND OPPORTUNITIES FOR DRUG DEVELOPMENT.

This review aimed to evaluate commonly used preclinical small animal models of osteoarthritis (OA) and their utility in drug development pipelines. The authors conducted a comprehensive overview of both spontaneous and experimentally-induced small animal OA models, examining their strengths, limitations, and practical considerations for pharmaceutical research. The review identified that while various animal models exist to study OA pathogenesis and progression, there is limited published evidence regarding their technical reliability and ability to accurately predict clinical outcomes in humans. The findings highlight important implications for translational research, suggesting that better standardization of these models, improved reproducibility measures, and more appropriate outcome measures are needed to enhance their value in developing effective OA therapies and understanding disease mechanisms that could inform clinical management strategies.

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This study investigated how Bushen Zhuangjin Decoction (BZD), a traditional Chinese medicine formulation, affects chondrocyte function and the SOX9 regulatory pathway in osteoarthritis treatment. Researchers treated cultured rat chondrocytes with different concentrations of BZD-containing serum and assessed cell viability, gene expression, protein levels, and inflammatory markers using MTT assays, flow cytometry, qRT-PCR, Western blot, and immunofluorescence techniques.

The findings demonstrated that BZD treatment enhanced chondrocyte viability, reduced cell death, and significantly increased expression of key cartilage matrix genes (SOX9, aggrecan, and type II collagen) while decreasing inflammatory factors, with medium-concentration BZD showing optimal effects. This suggests BZD promotes a beneficial chondrocyte phenotype characterized by enhanced matrix production and reduced inflammation.

These results indicate that BZD may offer a promising therapeutic approach for osteoarthritis by targeting chondrocyte repair mechanisms, though clinical translation and integration with conventional physiotherapy approaches for cartilage preservation would require further investigation.

CLINICAL AND RADIOLOGICAL OUTCOME OF MASON-JOHNSTON TYPES III AND IV RADIAL HEAD FRACTURES TREATED BY AN ON-TABLE RECONSTRUCTION.

This study evaluated the clinical and radiological outcomes of "on-table" (ex situ) reconstruction for severely comminuted radial head fractures (Mason-Johnston types III and IV) as an alternative to radial head resection or arthroplasty. The researchers retrospectively analyzed 14 patients treated with this technique between 2010-2020, using functional outcome scores (DASH, MEPI, Broberg-Morrey), range of motion measurements, and radiological assessment at a mean follow-up of 50 months.

The study found that on-table reconstruction achieved good functional outcomes with mean scores of 87 (MEPI), 13 (DASH), and 92 (Broberg-Morrey points), though patients showed some limitations in forearm rotation (pronation 65°, supination 66°) and mild extension loss (8°). Complete or partial bone union occurred in 13/14 cases with no avascular necrosis, though post-traumatic osteoarthritis developed in 11 cases and 5 patients required implant removal due to impingement.

For clinical practice, this technique offers a viable reconstructive option for complex radial head fractures that preserves native anatomy and allows early mobilization, though patients and physiotherapists should expect some residual stiffness and the potential need for secondary procedures during rehabilitation.

UNSUPERVISED MACHINE-LEARNING ALGORITHMS FOR THE IDENTIFICATION OF CLINICAL PHENOTYPES IN THE OSTEOARTHRITIS INITIATIVE DATABASE.

This study aimed to identify distinct osteoarthritis patient subgroups using machine learning algorithms applied to the large Osteoarthritis Initiative database with 157 baseline variables. Two different unsupervised clustering methods (Deep Embedded Clustering and Multiple Factor Analysis with Clustering) were used to analyze patient data and track outcomes over 8-9 years.

Both algorithms identified similar phenotypes: a "comorbid" cluster characterized by higher BMI, multiple health conditions, and low physical activity; a younger, more physically active group; and an elderly cluster with functional limitations but lower disease impact. Over the follow-up period, all clusters showed stable pain trajectories except for one pain measure, declining physical activity levels, and different patterns of joint space changes.

These findings suggest that osteoarthritis patients can be meaningfully stratified into distinct phenotypes that may respond differently to treatments, which could inform personalized rehabilitation approaches and help identify patients most likely to benefit from specific disease-modifying interventions in clinical trials.

VARIABILITY OF FUNCTIONAL KNEE PHENOTYPE FOR CORONAL ALIGNMENT IN ADVANCED VARUS KNEE OSTEOARTHRITIS IN THE JAPANESE POPULATION.

This study examined functional knee phenotypes based on coronal alignment patterns in 879 Japanese patients with advanced varus knee osteoarthritis, using CT imaging to measure hip-knee-ankle angle (HKA), femoral mechanical angle (FMA), and tibial mechanical angle (TMA). The researchers identified remarkable diversity in alignment patterns, finding 73 distinct phenotypes in males and 150 in females, with significant sex differences in overall alignment angles. Key findings showed that Japanese patients had more severe varus deformities compared to previously reported Caucasian populations, and in most cases (52-61%), tibial deformity contributed more to the overall varus alignment than femoral deformity. These results suggest that osteoarthritis management and surgical planning should account for ethnic variations and individual phenotypic patterns, as the predominant tibial contribution to varus deformity in Japanese patients may require different therapeutic approaches compared to treatment protocols developed for Caucasian populations.

CHOLESTEROL, SYSTEMIC INFLAMMATION, INTERLEUKIN-1Β, AND OSTEOARTHRITIS RISK - ALIGNING ANIMAL MODELS WITH SPECIFIC PATIENT ENDOTYPES PROVIDES NOVEL INSIGHTS.

I apologize, but I cannot provide a summary as the abstract is listed as "NA" (not available). To write an accurate and meaningful summary focusing on the study objective, key methods, findings regarding osteoarthritis phenotypes/subgroups, and implications for management or physiotherapy, I would need access to the actual abstract content.

If you could provide the complete abstract, I would be happy to create a concise 3-4 sentence summary in plain language that addresses the relationship between cholesterol, systemic inflammation, IL-1β, and osteoarthritis risk, particularly regarding patient endotypes and their alignment with animal models.

PATTERNS OF PROGRESSION DIFFER BETWEEN KELLGREN-LAWRENCE 2 AND 3 KNEES FULFILLING DIFFERENT DEFINITIONS OF A CARTILAGE-MENISCUS PHENOTYPE IN THE FOUNDATION FOR NATIONAL INSTITUTES OF HEALTH OSTEOARTHRITIS BIOMARKERS STUDY (FNIH).

This study aimed to evaluate three different MRI-based definitions of a cartilage-meniscus osteoarthritis phenotype and examine how well they predict disease progression in knees with moderate (KL2) versus more severe (KL3) radiographic changes over 48 months. Using data from 485 knees in the FNIH study, researchers applied three modified ROAMES definitions that differed in their thresholds for cartilage damage, then tracked which knees developed both radiographic worsening and increased pain ("composite cases").

The key finding was that the cartilage-meniscus phenotype predicted progression differently depending on disease severity: in KL2 knees, having this phenotype increased the odds of progression by 1.9-2.5 times across all three definitions, while in KL3 knees, the phenotype was actually associated with reduced odds of progression (0.3-0.6 times).

These results suggest that MRI-based phenotyping may be most useful for identifying high-risk patients in earlier-stage osteoarthritis (KL2), while more advanced cases (KL3) may progress regardless of phenotype, indicating that different management strategies and intervention timing may be needed based on radiographic severity at presentation.

FEASIBILITY OF A RANDOMISED CONTROLLED TRIAL OF TWO TYPES OF WRITTEN INFORMATION FOR PEOPLE WITH KNEE OSTEOARTHRITIS.

This feasibility study aimed to test whether a randomized controlled trial comparing two types of written information could be successfully conducted in community pharmacies with people with knee osteoarthritis. The researchers recruited 64 participants through pharmacy staff using clinical criteria and randomized them to receive either a novel information booklet or standard written resources, measuring outcomes including OA knowledge, illness perceptions, and fear of movement at baseline and 4 weeks.

The study demonstrated successful feasibility with good recruitment rates (2.7 participants per pharmacy per week), minimal dropouts, and positive feedback from both pharmacists and participants. Notably, one-quarter of participants had not previously received a formal knee OA diagnosis, and the novel booklet significantly improved OA knowledge scores compared to standard materials, though it did not change illness perceptions.

The findings suggest community pharmacies represent a promising, accessible setting for delivering osteoarthritis education and potentially initiating care pathways. For physiotherapy practice, this indicates that enhanced patient education materials can effectively improve knowledge about OA, though additional interventions beyond written information alone may be needed to meaningfully change patients' beliefs and perceptions about their condition.

GAIT VARIABILITY TO PHENOTYPE COMMON ORTHOPEDIC GAIT IMPAIRMENTS USING WEARABLE SENSORS.

This study investigated whether gait variability measures from wearable foot sensors during a 6-minute walk test could distinguish between different causes of mobility impairment, specifically lumbar spinal stenosis (LSS) versus knee osteoarthritis (KOA). The researchers used bilateral foot-mounted inertial measurement units to collect gait data from 10 patients each with LSS and KOA, plus 10 healthy controls, analyzing 11 gait parameters across four domains (pace, rhythm, asymmetry, variability). While both patient groups showed impaired gait compared to controls, only stride length variability could differentiate between the two conditions, with LSS patients demonstrating significantly higher variability during minutes 3-4 of the walk test. These findings suggest that gait variability analysis, particularly during the middle portion of endurance walking tests, could serve as a biomarker to phenotype different underlying causes of mobility impairment, potentially enabling more targeted rehabilitation approaches that address neurological control issues in LSS versus structural joint problems in KOA.

THE CURRENT STATE OF THE OSTEOARTHRITIS DRUG DEVELOPMENT PIPELINE: A COMPREHENSIVE NARRATIVE REVIEW OF THE PRESENT CHALLENGES AND FUTURE OPPORTUNITIES.

**Study Objective:** This narrative review aimed to critically assess the current osteoarthritis drug development pipeline, focusing on disease-modifying OA drugs (DMOADs) and identifying challenges and opportunities for future therapeutic development.

**Key Methods:** The authors conducted a comprehensive narrative review examining current DMOAD definition, clinical trial methodologies, outcome assessment tools, and results from recent clinical trials of novel drug candidates.

**Main Findings Regarding Phenotypes/Subgroups:** The review highlighted that future DMOADs should be more precisely targeted based on emerging clinical phenotypes and molecular endotypes of OA, rather than using a one-size-fits-all approach, and called for an updated consensus definition of DMOADs involving all major stakeholders.

**Implications for Management:** The findings suggest that personalized treatment approaches based on OA phenotyping could improve drug development success rates and clinical outcomes, potentially leading to more effective targeted therapies that could complement or enhance current physiotherapy and rehabilitation strategies.

ANALYSIS OF GUT MICROBIOME COMPOSITION, FUNCTION, AND PHENOTYPE IN PATIENTS WITH OSTEOARTHRITIS.

This study aimed to investigate differences in gut microbiome composition, function, and phenotype between osteoarthritis (OA) patients and healthy controls to better understand the relationship between gut bacteria and OA development. The researchers analyzed stool samples using advanced DNA sequencing techniques and statistical methods, adjusting for age, gender, and BMI to identify specific bacterial differences and potential biomarkers.

The study identified distinct gut microbiome patterns in OA patients, with certain harmful bacterial groups being more abundant in OA patients while beneficial bacteria were reduced in healthy controls. Functional analysis revealed that OA patients had altered bacterial metabolism, including decreased amino acid and ATP metabolism but increased glucose metabolism, along with a shift toward more aerobic and gram-negative bacteria.

These findings suggest that gut microbiome analysis could potentially help identify OA patients and provide new targets for treatment, though the implications for physiotherapy and clinical management require further research to determine if gut-targeted interventions (such as probiotics or dietary modifications) could complement traditional musculoskeletal rehabilitation approaches.

RADIOLOGICAL EVALUATION OF THE PHENOTYPE OF INDIAN OSTEOARTHRITIC KNEES BASED ON THE CORONAL PLANE ALIGNMENT OF THE KNEE CLASSIFICATION (CPAK).

This study aimed to classify knee alignment patterns in the Indian population using the Coronal Plane Alignment of the Knee (CPAK) classification system, comparing healthy young adults with elderly osteoarthritis patients. The researchers analyzed long-leg radiographs from 1000 knees (500 from each group), measuring alignment angles and joint line obliquity to categorize knees into nine distinct CPAK phenotypes. Key findings revealed that healthy young adults predominantly showed CPAK Type II alignment (25.6%), while osteoarthritis patients were primarily Type I (58.8%), characterized by constitutional varus alignment with an apex-distal joint line orientation. These distinct phenotypic patterns suggest that understanding a patient's constitutional alignment could optimize surgical planning for total knee arthroplasty and potentially inform conservative management strategies, as the predominant varus alignment pattern in Indian osteoarthritis patients may require specific consideration in treatment approaches.

KNEE ALIGNMENT CORRECTION BY HIGH TIBIAL OSTEOTOMY REDUCES SYMPTOMS AND SYNOVIAL INFLAMMATION IN KNEE OSTEOARTHRITIS ACCOMPANIED BY MACROPHAGE PHENOTYPIC CHANGE FROM M1 TO M2.

This study investigated whether high tibial osteotomy (HTO) surgery to correct knee alignment could improve the biological environment inside osteoarthritic knee joints. The researchers collected synovial tissue and fluid samples from 31 knee osteoarthritis patients during their initial HTO surgery and again during plate removal, analyzing changes in gene expression, inflammatory markers, and macrophage types using various laboratory techniques.

The key finding was that alignment correction led to a shift in macrophage phenotype from the harmful M1 type (pro-inflammatory) to the beneficial M2 type (anti-inflammatory), accompanied by reduced inflammatory gene expression and decreased synovial inflammation scores. Laboratory experiments revealed that cartilage fragments drive M1 macrophage activation, and patients with better clinical outcomes showed higher expression of M2-related genes.

These results suggest that correcting knee alignment through HTO not only improves symptoms but also creates a healthier joint environment by reducing harmful inflammation, which has important implications for understanding how mechanical interventions can influence the biological processes in osteoarthritis and potentially inform physiotherapy approaches targeting joint alignment and loading.

DISPARITIES IN MORBIDITY AFTER SPINAL CORD INJURY ACROSS INSURANCE TYPES IN THE UNITED STATES.

This study examined how insurance type affects health outcomes in adults with traumatic spinal cord injuries (TSCIs) by comparing morbidity patterns between privately insured (n=9,081) and Medicare beneficiaries (n=7,645). The researchers analyzed baseline prevalence and 4-year incidence rates of psychological, cardiometabolic, and musculoskeletal conditions, using survival models to calculate adjusted hazard ratios while controlling for demographics and existing health conditions.

Medicare beneficiaries with TSCI consistently showed higher rates of comorbidities across all categories, with notable differences including depression (37.6% vs 24.2% incidence), type 2 diabetes (22.5% vs 12.9%), and osteoarthritis (42.1% vs 34.6% over 4 years). After adjusting for confounding factors, Medicare beneficiaries had significantly higher risks for developing psychological conditions (40% increased hazard) and cardiometabolic conditions (21% increased hazard) compared to privately insured individuals.

These findings highlight significant healthcare disparities that have important implications for rehabilitation planning, suggesting that individuals with government insurance may require more intensive monitoring and preventive interventions for secondary complications following spinal cord injury.

DO ASSOCIATIONS WITH HAND OA VARY BY KNEE OSTEOARTHRITIS PHENOTYPE? CROSS-SECTIONAL DATA FROM THE MULTICENTER OSTEOARTHRITIS STUDY.

This study aimed to determine whether the association between hand and knee osteoarthritis (OA) varies depending on specific knee OA phenotypes, which could help refine how we define multi-joint OA. Researchers analyzed data from 2,493 participants in the Multicenter Osteoarthritis Study, using hand photographs to score hand OA severity and knee X-rays to identify different knee OA phenotypes (including symptomatic OA, hyper/atrophic subtypes, and non-traumatic OA). The study found modest associations between hand and knee OA overall, with slightly stronger associations for symptomatic knee OA and knee OA excluding post-traumatic cases, though most phenotype-specific associations were not statistically significant. These findings suggest that hand-knee OA associations are fairly consistent across different knee OA subtypes, indicating that current approaches to identifying multi-joint OA may not need major refinement based on knee phenotypes, though clinicians should be aware that symptomatic and non-traumatic knee OA may have slightly stronger systemic components.

KNEE IMMOBILIZATION REPRODUCES KEY ARTHROFIBROTIC PHENOTYPES IN MICE.

This study aimed to develop a mouse model of knee arthrofibrosis (joint stiffness and contracture) without osteoarthritis to better understand this condition and test potential treatments. Researchers immobilized the knees of 144 female mice for either 4 or 8 weeks, then allowed remobilization for 0-4 weeks, measuring joint range of motion and examining tissue changes under microscope.

The study identified distinct phenotypes based on immobilization duration: mice with 4-week immobilization showed some recovery of joint motion during remobilization, while those with 8-week immobilization developed persistent, severe contractures (joint angles around 72-82° compared to normal) that did not improve even after 4 weeks of remobilization. Importantly, no cartilage damage typical of osteoarthritis was observed, confirming this was pure arthrofibrosis.

These findings suggest there may be a critical time threshold (around 8 weeks) after which joint contractures become largely irreversible, with important implications for physiotherapy timing - early intervention within the first month of immobilization may be crucial for preventing permanent joint stiffness in clinical practice.

OSTEOARTHRITIS, AN OLD WINE IN A NEW BOTTLE!

This editorial examines the challenges and future directions in osteoarthritis (OA) research, highlighting the need to move beyond traditional "one-size-fits-all" approaches to more personalized medicine strategies. The authors identify key gaps including the lack of robust early OA classification criteria, limited disease-modifying treatments, and insufficient patient stratification methods, while proposing solutions through advanced technologies like artificial intelligence and genomic profiling from omics platforms. The paper emphasizes that future OA management must focus on identifying distinct phenotypic and endotypic disease variants, supported by reliable biomarkers for early disease detection and patient subgrouping. For clinicians and physiotherapists, this suggests that personalized treatment approaches based on individual patient phenotypes and disease subtypes will likely become essential for effective OA management, moving away from current generalized treatment protocols toward more targeted interventions.

MEDIAL PIVOT DESIGNS VERSUS CONVENTIONAL BEARING TYPES IN PRIMARY TOTAL KNEE ARTHROPLASTY: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS.

**Study Objective:** This systematic review and meta-analysis aimed to compare clinical outcomes between medial pivot (MP) total knee arthroplasty designs and conventional bearing types (cruciate-retaining, posterior-stabilized, ultracongruent, or mobile-bearings) in primary knee replacement surgery.

**Key Methods:** The researchers analyzed 8 randomized controlled trials involving 725 knees (350 MP, 375 conventional), with most studies comparing MP to posterior-stabilized designs, measuring clinical function scores, patient-reported outcomes, range of motion, and complications.

**Main Findings:** The meta-analysis found no significant differences between MP and posterior-stabilized designs at any time point, including similar Oxford Knee Score, range of motion, and Western Ontario Arthritis Index scores at 12-24 months follow-up, suggesting both designs perform equally well clinically.

**Clinical Implications:** These findings indicate that physiotherapists and clinicians can expect similar rehabilitation outcomes and functional recovery regardless of whether patients receive MP or conventional posterior-stabilized knee replacements, though more research is needed comparing MP designs to other bearing types.

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This study investigated the potential of sodium tanshinone IIA sulfonate (STS) to promote meniscus healing by modulating immune responses, addressing the limited natural healing capacity of meniscal injuries that often progress to osteoarthritis. The researchers used in vitro cell culture studies to examine STS effects on macrophage polarization and meniscal cell protection, followed by in vivo testing of an STS-loaded hybrid scaffold in rabbit models of meniscal injury.

Key findings revealed that STS successfully shifted macrophages from the inflammatory M1 phenotype to the tissue-repair promoting M2 phenotype, while protecting meniscal cells from inflammation-induced damage through inhibition of specific cellular pathways. The study demonstrated that this immune modulation approach, delivered via a specialized scaffold combining mechanical support with biological factors, achieved effective meniscus regeneration and joint protection in animal models.

These results suggest that targeting macrophage phenotypes could represent a promising therapeutic strategy for meniscal injuries, potentially informing future regenerative medicine approaches that could delay or prevent osteoarthritis progression following meniscal damage.

METABOLOMIC PHENOTYPES REFLECT PATIENT SEX AND INJURY STATUS: A CROSS-SECTIONAL ANALYSIS OF HUMAN SYNOVIAL FLUID.

This cross-sectional study aimed to identify distinct metabolic phenotypes in synovial fluid based on knee injury type and patient sex to better understand post-traumatic osteoarthritis (PTOA) development. The researchers analyzed synovial fluid from 33 arthroscopy patients using liquid chromatography mass spectrometry, comparing metabolic profiles across different injury pathologies (ACL vs. meniscus injuries) and between male and female participants.

The study identified distinct metabolic phenotypes for different injury types, with variations in amino acid metabolism, lipid oxidation, and inflammatory pathways, suggesting that ligament and meniscus injuries trigger different endogenous repair mechanisms. Additionally, sex-specific metabolic differences were detected, including variations in cervonyl carnitine concentrations between males and females.

These findings suggest that personalized rehabilitation approaches considering both injury type and patient sex may be beneficial, and ongoing metabolomic monitoring could help track PTOA progression and identify potential therapeutic targets for preventing or slowing disease development.

DEEP LEARNING PHENOTYPE AUTOMATION AND COHORT ANALYSES OF 1,946 KNEES USING THE CORONAL PLANE ALIGNMENT OF THE KNEE CLASSIFICATION.

This study aimed to automate knee alignment phenotyping using the Coronal Plane Alignment of the Knee (CPAK) classification through deep learning and analyze phenotype distributions in a large patient cohort. The researchers developed a deep learning algorithm to automatically measure knee alignment parameters from full-limb radiographs in 1,946 knees, validating it against expert surgeon assessments with high accuracy (correlation 0.89-0.91). Key findings showed that women had more valgus (outward-angled) knee phenotypes while men showed more varus alignment, and patients with more severe arthritis (higher Kellgren-Lawrence grades 2-4) demonstrated greater varus deformity compared to those with minimal arthritis. These results suggest that knee alignment phenotyping could be efficiently automated for clinical use, but sex-specific differences and arthritis severity should be considered when applying this classification system in preoperative planning for total knee replacement and potentially in designing targeted physiotherapy interventions for different knee alignment patterns.

CELL MORPHOLOGY AS A BIOLOGICAL FINGERPRINT OF CHONDROCYTE PHENOTYPE IN CONTROL AND INFLAMMATORY CONDITIONS.

This study aimed to determine whether chondrocyte cell shape could serve as a biological fingerprint to distinguish between healthy and inflammatory cell phenotypes in osteoarthritis research. The researchers used advanced image analysis to measure seven shape characteristics (area, length, width, circularity, aspect ratio, roundness, solidity) of thousands of chondrocytes from both healthy bovine and human osteoarthritic cartilage, comparing cells under normal conditions versus inflammatory stimulation with IL-1β, while also analyzing gene expression patterns.

The analysis revealed distinct morphological fingerprints that could reliably differentiate between control and inflammatory chondrocyte phenotypes: healthy bovine chondrocytes showed higher aspect ratios under normal conditions but increased circularity and width when inflamed, while human OA chondrocytes displayed greater roundness normally but increased length and area when inflamed. Importantly, all shape measurements correlated with the expression of genes involved in cartilage matrix production and inflammation regulation.

These findings suggest that simple cell shape analysis could provide a rapid, cost-effective tool for researchers and clinicians to assess chondrocyte health and response to treatments, potentially accelerating the development and testing of new therapeutic approaches for osteoarthritis management and cartilage repair strategies.

CERIA NANOPARTICLES ALLEVIATED OSTEOARTHRITIS THROUGH ATTENUATING SENESCENCE AND SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE IN SYNOVIOCYTES.

This study investigated whether ceria nanoparticles (CeNP) could treat osteoarthritis by targeting cellular senescence in joint tissues. The researchers used both laboratory cell cultures (treating synoviocytes with hydrogen peroxide to induce senescence) and animal models, examining the effects of CeNP on senescence markers, inflammatory proteins, and cartilage damage through immunohistochemistry and tissue staining.

The key findings revealed that CeNP reduced cellular senescence and the harmful inflammatory secretions (SASP) associated with aged synoviocytes by scavenging reactive oxygen species (ROS) and blocking the NFκB inflammatory pathway. In the animal model, intra-articular injection of CeNP led to less cartilage destruction compared to untreated osteoarthritis.

These results suggest that targeting senescent cells represents a promising new therapeutic approach for osteoarthritis, potentially offering clinicians and physiotherapists a novel treatment strategy that addresses underlying cellular aging processes rather than just symptoms. However, translation to human clinical applications would require further research on safety and efficacy in clinical trials.

BONE MARROW-DERIVED DEDIFFERENTIATED FAT CELLS EXHIBIT SIMILAR PHENOTYPE AS BONE MARROW MESENCHYMAL STEM CELLS WITH HIGH OSTEOGENIC DIFFERENTIATION AND BONE REGENERATION ABILITY.

This study aimed to compare the phenotypic characteristics and bone regeneration potential of dedifferentiated fat cells (DFATs) and mesenchymal stem cells (MSCs) derived from different tissue sources in osteoarthritis patients. Researchers isolated bone marrow-derived DFATs (BM-DFATs), bone marrow MSCs, subcutaneous fat-derived DFATs, and adipose stem cells from patients undergoing knee replacement surgery, then analyzed their cellular properties in laboratory tests and evaluated their bone healing capacity in a mouse fracture model.

The key finding was that BM-DFATs exhibited nearly identical characteristics to bone marrow MSCs, including superior ability to form bone cells and enhanced bone regeneration compared to fat-derived cells. Both BM-DFATs and bone marrow MSCs showed stronger bone-forming potential and weaker fat-forming tendencies than their subcutaneous counterparts, and both effectively improved bone mineral density when injected at fracture sites.

These results suggest that the tissue source (bone marrow versus fat tissue) significantly influences the therapeutic potential of these regenerative cells, with bone marrow-derived cells being more suitable for bone repair applications. This research has implications for developing targeted cell-based therapies for patients with bone healing problems, particularly those with fracture nonunions who may benefit from bone marrow-derived cellular treatments.

METABOLIC AND INFLAMMATORY PROFILES DEFINE PHENOTYPES WITH CLINICAL RELEVANCE IN FEMALE KNEE OSTEOARTHRITIS PATIENTS WITH JOINT EFFUSION.

This study aimed to identify distinct knee osteoarthritis (OA) phenotypes in women with joint effusion by analyzing their metabolic and inflammatory characteristics. Researchers used machine learning methods to analyze 45 parameters (including body measurements, metabolic factors, and inflammation markers) from 168 female knee OA patients, then tracked their symptoms and joint damage progression over two years.

The analysis revealed four clinically meaningful phenotypes: KOIP-1 (obesity-driven with high inflammation), KOIP-2 (metabolically healthy with mild inflammation), KOIP-3 (high inflammation without metabolic issues), and KOIP-4 (metabolic problems with low inflammation and cardiovascular risk factors). These phenotypes showed significant differences in pain levels, functional disability, and rate of joint damage progression over time.

These findings suggest that knee OA patients should be categorized into subgroups based on their metabolic and inflammatory profiles to enable more targeted, personalized treatment approaches rather than using a one-size-fits-all management strategy.

THE CORONAL PLANE ALIGNMENT OF THE KNEE CLASSIFICATION DOES NOT CORRELATE WITH THE FUNCTIONAL KNEE PHENOTYPE CLASSIFICATION.

This study compared two knee alignment classification systems - the functional knee phenotypes classification and the Coronal Plane Alignment of the Knee (CPAK) classification - in 520 patients undergoing total knee arthroplasty, using navigation system data to measure anatomical parameters during surgery. The researchers compared hip-knee-ankle angle (HKA) measurements from functional phenotyping with arithmetic hip-knee-ankle angle (AHKA) calculations from CPAK classification in the same patients.

The study found significant differences between HKA and AHKA measurements (mean 3.0° vs 1.8° varus respectively), with only weak correlation between the two methods and no relationship between HKA values and CPAK classifications. These findings suggest that the two classification systems capture different aspects of knee alignment and should be viewed as complementary rather than interchangeable approaches for phenotyping patients with knee osteoarthritis, though their clinical relevance for guiding treatment decisions remains unclear.

RECEPTOR TYROSINE KINASE C-KIT PROMOTES A DESTRUCTIVE PHENOTYPE OF FLS IN OSTEOARTHRITIS VIA INTRACELLULAR EMT SIGNALING.

This study investigated how receptor tyrosine kinase C-KIT promotes destructive cellular behavior in osteoarthritis (OA) through epithelial-mesenchymal transition (EMT) signaling pathways. The researchers analyzed synovial tissue from OA patients, performed cell culture experiments with fibroblast-like synoviocytes (FLS) and cartilage cells, and tested interventions in a rat OA model to understand the molecular mechanisms involved.

The key finding was that 40% of OA patients showed elevated N-cadherin (an EMT marker), and these samples had higher inflammation and more destructive FLS that damaged cartilage cells when cultured together. The study revealed that C-KIT protein drives this destructive FLS phenotype by activating EMT signaling through a specific molecular pathway involving GSK3β and SNAIL proteins, while blocking C-KIT protected joints in the rat model.

These findings identify two distinct OA phenotypes - one with high EMT signaling (40% of patients) associated with more aggressive joint destruction, and another with lower EMT activity. For clinical management, this suggests that patients with high EMT markers might benefit from targeted anti-inflammatory treatments or C-KIT inhibitors, while standard physiotherapy approaches may be more suitable for the low-EMT phenotype, potentially leading to more personalized OA treatment strategies

GEOGRAPHIC VARIATION IN KNEE PHENOTYPES BASED ON THE CORONAL PLANE ALIGNMENT OF THE KNEE CLASSIFICATION: A SYSTEMATIC REVIEW.

This systematic review examined geographic differences in knee alignment phenotypes using the Coronal Plane Alignment of the Knee (CPAK) classification, which categorizes knees into 9 types based on limb alignment and joint line positioning. The authors analyzed 7 studies encompassing 5,964 knees from various countries including Belgium, Taiwan, India, France, Japan, and Australia. Key findings revealed significant geographic variation in knee phenotype distributions: in healthy knees, CPAK Type II was most prevalent in Belgium and Taiwan (39%), while in arthritic knees, CPAK Type I dominated in France, India, and Japan, but Type II was most common in Australia. These findings suggest that knee alignment patterns vary substantially by geographic region, highlighting the need for population-specific approaches to knee arthroplasty planning and potentially informing targeted rehabilitation strategies based on regional phenotype prevalence.

CLINICAL PHENOTYPES AND PROGNOSTIC FACTORS IN PERSONS WITH HIP OSTEOARTHRITIS UNDERGOING TOTAL HIP ARTHROPLASTY: PROTOCOL FOR A LONGITUDINAL PROSPECTIVE COHORT STUDY (HIPPROCLIPS).

This study protocol (HIPPROCLIPS) aims to identify clinical phenotypes and prognostic factors in 200 people with hip osteoarthritis undergoing total hip arthroplasty (THA), with a particular focus on how psychological factors like trauma, mental health, and pain-related beliefs influence outcomes. The researchers will use comprehensive assessments including pain sensitivity testing, psychological questionnaires, and functional measures at multiple time points (before surgery through 12 months post-surgery), analyzing data with advanced statistical methods including machine learning algorithms. The study seeks to identify distinct patient subgroups both before and after surgery, and determine which pre-operative and early post-operative factors predict pain and disability outcomes following THA. These findings could enable precision medicine approaches for hip OA patients, potentially allowing clinicians and physiotherapists to tailor pre-operative counseling, surgical timing, and post-operative rehabilitation strategies based on individual patient phenotypes and risk profiles.

MITOCHONDRIAL CALCIUM NANOREGULATORS REVERSE THE MACROPHAGE PROINFLAMMATORY PHENOTYPE THROUGH RESTORING MITOCHONDRIAL CALCIUM HOMEOSTASIS FOR THE TREATMENT OF OSTEOARTHRITIS.

This study aimed to develop targeted nanoparticles to reduce mitochondrial calcium overload in macrophages as a novel treatment approach for osteoarthritis. The researchers synthesized specialized nanoparticles (METP NPs) that specifically target mitochondria to block excess calcium influx, then tested their effects on inflammatory responses in mouse bone marrow-derived macrophages using fluorescence imaging, cellular assays, and metabolic analysis.

The key finding was that osteoarthritis macrophages exhibit elevated mitochondrial calcium levels that drive a proinflammatory phenotype, and the METP nanoparticles successfully reversed this inflammatory state by restoring normal calcium balance. The nanoparticles worked by inhibiting specific metabolic pathways (aspartate-arginosuccinate shunt) and reducing harmful reactive oxygen species production in mitochondria.

These results suggest that targeting mitochondrial calcium dysregulation could represent a new therapeutic strategy for osteoarthritis management, potentially offering more precise anti-inflammatory treatment compared to current approaches that broadly suppress immune responses.

OSTEOARTHRITIS, PART OF LIFE OR A CURABLE DISEASE? A BIRD'S-EYE VIEW.

This narrative review examined osteoarthritis (OA) as a complex disease, exploring whether it represents normal aging or a treatable condition. The authors conducted a broad overview of OA pathophysiology, disease burden, and current therapeutic approaches, drawing on existing literature to analyze the challenges in OA management and drug development.

The review emphasizes that OA exists in multiple distinct forms, with different underlying biological pathways (endotypes) and clinical presentations (phenotypes), making it challenging to develop universal treatments. Key findings highlight that structural joint changes often occur without symptoms, current treatments rely heavily on non-specific contextual effects rather than targeted therapeutic mechanisms, and drug development efforts targeting cartilage breakdown or repair have not yet succeeded in phase III trials.

The implications for clinical management include the need for earlier diagnosis, better characterization of OA subtypes through biomarkers and advanced imaging, and more precise patient selection for treatments. For physiotherapy and rehabilitation, this suggests that personalized approaches based on individual phenotypes may be more effective than one-size-fits-all interventions, though the review indicates current therapeutic effects remain limited regardless of approach.

OBESITY DEFINED MOLECULAR ENDOTYPES IN THE SYNOVIUM OF PATIENTS WITH OSTEOARTHRITIS PROVIDES A RATIONALE FOR THERAPEUTIC TARGETING OF FIBROBLAST SUBSETS.

This study aimed to identify distinct molecular subtypes (endotypes) of osteoarthritis based on obesity status by analyzing synovial tissue from multiple joints in obese versus normal-weight patients. Researchers used advanced molecular techniques including protein analysis, metabolic testing, and single-cell RNA sequencing on synovial fibroblasts from hand, hip, knee, and foot joints of 32 OA patients.

The study identified four distinct fibroblast endotypes, with obesity creating specific inflammatory patterns characterized by immune cell regulation and fibroblast activation, including elevated markers like CHI3L1 in obese patients - importantly, these obesity-related changes occurred in both weight-bearing joints (hip, knee) and non-weight-bearing joints (hand). These findings suggest that OA patients could be stratified into subgroups based on obesity status and specific molecular signatures, potentially allowing for more targeted therapeutic approaches rather than treating all OA patients the same way.

This personalized medicine approach could improve clinical trial success rates and help physiotherapists and clinicians better understand why certain patients may respond differently to treatments based on their weight status and underlying joint biology.

THE EFFECT OF ALLYL ISOTHIOCYANATE ON CHONDROCYTE PHENOTYPE IS MATRIX STIFFNESS-DEPENDENT: POSSIBLE INVOLVEMENT OF TRPA1 ACTIVATION.

This study investigated how the mechanical environment affects chondrocyte responses to TRPA1 activation, which may contribute to osteoarthritis progression. The researchers cultured chondrocytes from osteoarthritis patients on substrates of different stiffness (soft vs. stiff) and treated them with allyl isothiocyanate (AITC), a TRPA1 activator, then analyzed cell shape, protein expression, collagen production, and inflammation markers.

The key finding was that AITC treatment produced both beneficial and harmful effects on chondrocytes, but these effects were dependent on matrix stiffness - softer substrates enhanced the positive effects while reducing the negative ones. This suggests that the mechanical properties of cartilage tissue may influence how chondrocytes respond to therapeutic interventions, potentially offering a new approach for osteoarthritis treatment that considers both biochemical and biomechanical factors in rehabilitation strategies.

CULTURE-EXPANDED MESENCHYMAL STROMAL CELL THERAPY: DOES IT WORK IN KNEE OSTEOARTHRITIS? A PATHWAY TO CLINICAL SUCCESS.

This systematic review evaluated the effectiveness of culture-expanded mesenchymal stromal cells (MSCs) for treating knee osteoarthritis by analyzing 26 clinical trials involving 610 patients. The researchers examined key treatment parameters including MSC dose, tissue source, and delivery method, while also considering patient factors such as clinical phenotype, age, sex, and OA severity.

The study found generally positive effects, with MSCs improving pain and function in most trials (11-12 out of 15 randomized controlled trials) and showing cartilage protection or repair benefits in 18 out of 21 studies, though trends suggested moderate to higher MSC doses were more effective in select patient phenotypes.

The authors propose that successful MSC therapy requires matching specific OA patient subgroups (defined by both clinical phenotype and molecular characteristics) with appropriately "immunomodulatory fit" MSCs, emphasizing the need for personalized treatment approaches rather than one-size-fits-all protocols in future clinical trials.

DIFFERENTIAL EFFECTS OF HYPOXIA VERSUS HYPEROXIA OR PHYSOXIA ON PHENOTYPE AND ENERGY METABOLISM IN HUMAN CHONDROCYTES FROM OSTEOARTHRITIC COMPARED TO MACROSCOPICALLY NORMAL CARTILAGE.

This laboratory study investigated how different oxygen levels affect the behavior of cartilage cells (chondrocytes) from osteoarthritic versus healthy cartilage, aiming to better understand cellular mechanisms underlying osteoarthritis progression. Researchers cultured chondrocytes from osteoarthritic and macroscopically normal cartilage under three oxygen conditions: standard laboratory levels (18.9%), moderate physiological levels (6%), and low physiological levels (1%), then measured markers of cartilage breakdown and repair.

The study revealed distinct phenotypic differences between osteoarthritic and normal chondrocytes that varied with oxygen availability - osteoarthritic cells produced more cartilage-degrading enzymes (MMP13) under higher oxygen conditions, while normal chondrocytes showed better cartilage-building activity under low oxygen conditions. Additionally, osteoarthritic chondrocytes consistently relied more heavily on glycolytic metabolism regardless of oxygen levels, suggesting fundamental metabolic alterations in diseased cartilage.

These findings suggest that elevated oxygen levels in osteoarthritic joints may accelerate cartilage breakdown, highlighting the importance of considering tissue oxygenation in osteoarthritis management and potentially informing therapeutic strategies that target local tissue metabolism or oxygen regulation.

WNT16 REGULATION OF THE ARTICULAR CHONDROCYTE PHENOTYPE IN MICE.

This study investigated the role of WNT16, a signaling protein known to promote bone formation, in regulating articular cartilage cells (chondrocytes) that are central to osteoarthritis development. The researchers used mouse chondrocyte cell cultures and cartilage tissue samples, treating them with WNT16 protein and measuring changes in cell behavior, gene expression, and cartilage structure over different time periods.

The key findings revealed that WNT16 treatment increased chondrocyte proliferation by 20% and promoted an immature, more regenerative cell phenotype while reducing markers of mature cartilage cells. Additionally, WNT16 enhanced overall articular cartilage area and upregulated cartilage-protective genes in tissue samples, suggesting it supports cartilage maintenance and repair.

These results indicate that WNT16 may help preserve joint cartilage health by keeping chondrocytes in a more active, repair-oriented state, which could inform new therapeutic approaches for osteoarthritis management and potentially guide physiotherapy strategies aimed at promoting cartilage health through mechanical loading that might stimulate beneficial signaling pathways.

PENTOSAN POLYSULFATE SODIUM PROMOTES REDIFFERENTIATION TO THE ORIGINAL PHENOTYPE IN MICROMASS-CULTURED CANINE ARTICULAR CHONDROCYTES AND EXERTS MOLECULAR WEIGHT-DEPENDENT EFFECTS.

This study investigated how different molecular weights of pentosan polysulfate sodium (PPS), a heparin-like drug used to treat osteoarthritis in animals, affect cartilage cell behavior and phenotype. Researchers tested PPS variants (1,500-7,000 daltons) on canine cartilage cells using cell culture techniques, gene expression analysis, and protein measurements to assess cell viability, cartilage-specific markers, and tissue formation.

The findings revealed that PPS promotes cartilage cells to maintain their healthy, original phenotype in a molecular weight-dependent manner, with higher molecular weights (5,000-7,000 daltons) showing stronger effects. PPS treatment increased production of key cartilage components like collagen type II, aggrecan, and SOX9 without causing cell death, while also enhancing proteoglycan deposition - all markers of healthy cartilage.

These results suggest PPS could be a promising therapeutic target for osteoarthritis treatment, with higher molecular weight formulations potentially offering enhanced cartilage-protective benefits. For clinicians, this research supports the potential use of PPS as a disease-modifying treatment that may help preserve cartilage cell function and slow osteoarthritis progression, though human clinical trials would be needed to confirm these laboratory findings.

HYPOXIA-INDUCED WNT/Β-CATENIN SIGNALING ACTIVATION IN SUBCHONDRAL BONE OSTEOBLASTS LEADS TO AN OSTEOARTHRITIS-LIKE PHENOTYPE OF CHONDROCYTES IN ARTICULAR CARTILAGE.

This study investigated how oxygen deprivation (hypoxia) in the bone beneath joint cartilage affects the communication between bone cells and cartilage cells in osteoarthritis. The researchers examined tissue samples from OA patients and conducted laboratory experiments where they exposed bone-forming cells (osteoblasts) to low oxygen conditions, then tested how the substances these cells released affected cartilage cells (chondrocytes).

The key finding was that hypoxia activated a specific cellular pathway (Wnt/β-catenin signaling) in bone cells, causing them to release factors that pushed cartilage cells toward a disease-like state characterized by increased breakdown enzymes and reduced healthy cartilage proteins. The study identified a distinct subgroup of patients with severely damaged subchondral bone who showed particularly high levels of hypoxia markers.

These findings suggest that targeting the bone-cartilage communication pathway and addressing hypoxia in subchondral bone could represent new therapeutic approaches for osteoarthritis management, potentially complementing current physiotherapy strategies that focus primarily on joint movement and muscle strengthening.

CONCENTRATION-DEPENDENT EFFECTS OF LEPTIN ON OSTEOARTHRITIS-ASSOCIATED CHANGES IN PHENOTYPE OF HUMAN CHONDROCYTES.

This study investigated how different concentrations of leptin (a hormone linked to metabolic syndrome) affect cartilage cell behavior in osteoarthritis patients. Researchers treated chondrocytes from obese osteoarthritis patients with varying leptin concentrations (2-40 ng/ml) found in joint fluid and measured changes in cellular markers using molecular techniques.

The study found that higher leptin concentrations (20-40 ng/ml) caused chondrocytes to lose their healthy cartilage-producing characteristics, including decreased production of key cartilage components (SOX9, collagen, aggrecan) and increased production of cartilage-degrading enzymes (ADAMTS5, MMP13). These concentration-dependent effects were partially mediated through a protein called HES1, with the most severe changes occurring at the highest leptin levels.

The findings suggest that elevated leptin levels, commonly seen in patients with metabolic syndrome and women, may contribute to cartilage breakdown in osteoarthritis through direct effects on cartilage cells. This research supports the concept of metabolic osteoarthritis as a distinct phenotype and suggests that managing metabolic factors and leptin levels could be important therapeutic targets alongside traditional physiotherapy approaches for certain patient subgroups.

LATEST INSIGHTS IN DISEASE-MODIFYING OSTEOARTHRITIS DRUGS DEVELOPMENT.

This review examined the development of disease-modifying osteoarthritis drugs (DMOADs) aimed at preventing structural progression rather than just treating symptoms. The authors analyzed phase 2 and 3 clinical trials of various DMOADs targeting different tissue types (cartilage, synovium, and subchondral bone), including biologics, sprifermin, and bisphosphonates. Most trials failed to show satisfactory results, with the clinical heterogeneity of osteoarthritis identified as a primary reason for these failures, as different OA phenotypes may require different therapeutic approaches. The findings suggest that future DMOAD development should focus on phenotype-specific treatments, which has important implications for personalized rehabilitation strategies where physiotherapy interventions could be tailored to match specific OA endotypes and underlying disease mechanisms.

THE RELATIONSHIP BETWEEN CLINICAL PHENOTYPE AND KALLIKREIN-KININ BIOREGULATION IN DIFFERENT FORMS OF ARTHRITIS.

This study investigated how the kallikrein-kinin inflammatory system relates to clinical features across different types of arthritis, comparing osteoarthritis (OA), rheumatoid arthritis (RA), and gout patients. Researchers measured blood neutrophil markers, plasma inflammatory biomarkers, ultrasound features, and quality of life measures in 47 patients across the three arthritis types. The key finding was that despite similar pain and quality of life scores across all groups, each arthritis type showed distinct inflammatory profiles - OA patients had higher expression of certain neutrophil markers (K1B and KLK1), while RA patients showed elevated plasma inflammatory markers, and importantly, bradykinin receptor expression correlated with both pain levels and ultrasound inflammation markers. These results suggest that targeting the bradykinin receptor system could offer new therapeutic approaches for managing arthritis pain, potentially informing more personalized treatment strategies based on specific inflammatory phenotypes rather than traditional diagnostic categories alone.

IDENTIFYING MUSCLE FUNCTION-BASED PHENOTYPES ASSOCIATED WITH RADIOGRAPHIC PROGRESSION OF SECONDARY HIP OSTEOARTHRITIS.

This study aimed to identify muscle function-based phenotypes in women with hip osteoarthritis and determine their association with radiographic disease progression over 12 months. The researchers used cluster analysis on hip muscle strength data from 50 women with mild-to-moderate secondary hip OA, examining absolute strength, relative strength balance between muscle groups, and combined measures.

The analysis identified two distinct phenotypes, with 42% of patients showing radiographic progression (joint space narrowing >0.5mm). Importantly, the phenotype characterized by muscle strength imbalances—specifically relative weakness in hip flexion and internal rotation muscles—was significantly associated with disease progression (3.6 times higher odds), while absolute muscle strength levels showed no association with progression.

These findings suggest that muscle strength imbalances, rather than overall weakness, may be more important for predicting hip OA progression. This has important implications for physiotherapy, indicating that treatment should focus on correcting specific muscle imbalances rather than simply strengthening all hip muscles equally.

INFLUENCE OF MECHANICAL ALIGNMENT ON FUNCTIONAL KNEE PHENOTYPES AND CLINICAL OUTCOMES IN PRIMARY TKA: A 1-YEAR PROSPECTIVE ANALYSIS.

This study investigated whether mechanically aligned total knee arthroplasty (TKA) changes patients' preoperative functional knee phenotypes (limb, femoral, and tibial alignment patterns) and how these changes affect clinical outcomes at one year. The researchers analyzed long-leg radiographs before and after surgery in 59 patients with end-stage osteoarthritis, measuring changes in alignment phenotypes and correlating these with patient-reported outcome scores (Forgotten Joint Score, Oxford Knee Score, and WOMAC).

The study found that mechanically aligned TKA frequently altered patients' natural alignment patterns, with 42% experiencing limb phenotype changes and 41% experiencing femoral phenotype changes of more than ±1 category. Patients whose limb or femoral phenotypes changed by more than ±1 category had significantly worse functional outcomes and satisfaction scores at one year compared to those with minimal phenotype changes, while tibial phenotype changes showed no effect on outcomes.

These findings suggest that preserving patients' natural alignment patterns during TKA may be important for optimal outcomes, indicating that surgeons should consider limiting major corrections to limb and femoral alignment to stay within one phenotype category of the patient's preoperative state.

LONGITUDINAL CHANGES IN SHOULDER ARTHROPLASTY STRATIFIED BY AGE GROUPS, TYPES OF SURGICAL FACILITIES, AND GEOGRAPHICAL REGIONS IN KOREA FROM 2010 TO 2020.

This study examined trends in shoulder arthroplasty procedures in Korea over an 11-year period (2010-2020) using national health insurance data to analyze changes by age groups, surgical facilities, and geographical regions. The researchers analyzed longitudinal changes in total shoulder arthroplasty (TSA), hemiarthroplasty, and revision procedures across different patient populations and healthcare settings.

The key findings revealed distinct trends: TSA rates increased dramatically from 10.6 to 101.4 per million person-years, while hemiarthroplasty rates decreased from 6.4 to 3.7 per million, and revision arthroplasty rates increased from 0.8 to 2.3 per million. The steepest increases in TSA and revision procedures occurred in patients aged 70 and older, while hemiarthroplasty decreased across all age groups and regions, with revision procedures being more commonly performed in Seoul.

These findings suggest a significant shift in surgical practice patterns toward more comprehensive joint replacement procedures in older adults, likely reflecting improved surgical techniques and implant technology. For physiotherapy practice, this trend indicates an increasing need for specialized post-arthroplasty rehabilitation protocols, particularly for elderly patients undergoing TSA, and preparation for managing more complex cases given the rising revision rates.

AUTOPHAGY AND APOPTOSIS: REGULATORY FACTORS OF CHONDROCYTE PHENOTYPE TRANSITION IN OSTEOARTHRITIS.

This review examined how autophagy (cellular self-cleaning) and apoptosis (programmed cell death) regulate changes in chondrocyte (cartilage cell) characteristics during osteoarthritis progression. The authors synthesized existing literature on how external factors like aging and injury alter cellular metabolism, which in turn affects autophagy and apoptosis processes in cartilage cells. They found that as osteoarthritis progresses, disrupted autophagy and apoptosis cause chondrocytes to change into different cell types (phenotypes) with altered shape and function, contributing to cartilage breakdown. These findings suggest that targeting autophagy and apoptosis pathways could offer new therapeutic approaches to potentially reverse harmful chondrocyte changes and slow osteoarthritis progression, which may inform future rehabilitation strategies focused on protecting cartilage health.

GENDER-SPECIFIC DISTRIBUTION OF KNEE MORPHOLOGY ACCORDING TO CPAK AND FUNCTIONAL PHENOTYPE CLASSIFICATION: ANALYSIS OF 8739 OSTEOARTHRITIC KNEES PRIOR TO TOTAL KNEE ARTHROPLASTY USING ARTIFICIAL INTELLIGENCE.

This large-scale study analyzed knee alignment patterns in 8,739 osteoarthritic knees using AI-powered measurements to characterize gender-specific distributions according to CPAK (Coronal Plane Alignment of the Knee) and functional phenotype classifications. The researchers used artificial intelligence software to automatically measure standardized alignment parameters from preoperative long-leg radiographs of patients scheduled for total knee replacement surgery between 2009-2021.

The study revealed significant gender differences in knee morphology, with men more commonly presenting with varus (bow-legged) alignment (68.5% vs 50.8% in women), while women showed more neutral and valgus patterns. Men predominantly presented with CPAK Type I (38.8%) and Type II (27.3%) morphologies, whereas women were more evenly distributed across Types I, II, and III, indicating greater morphological variability in female osteoarthritic knees.

These findings have important implications for personalized surgical planning in total knee replacement, as understanding gender-specific morphological patterns could help surgeons better predict alignment challenges and optimize implant positioning. The research also supports the development of gender-specific rehabilitation protocols and may inform physiotherapy approaches by highlighting the different mechanical patterns that contribute to knee osteoarthritis progression in men versus women.

STUDY OF HYDROGEN SULFIDE BIOSYNTHESIS IN SYNOVIAL TISSUE FROM DIABETES-ASSOCIATED OSTEOARTHRITIS AND ITS INFLUENCE ON MACROPHAGE PHENOTYPE AND ABUNDANCE.

This study investigated how hydrogen sulfide (H₂S) biosynthesis differs in osteoarthritis patients with type 2 diabetes and its effects on inflammatory cell behavior in joint tissue. Researchers analyzed synovial tissue from diabetic OA patients and used laboratory cell culture models with high glucose conditions, plus tested H₂S donor treatment in living animal models. They found that diabetic OA patients had reduced H₂S-producing enzymes in their joint tissue, and high glucose conditions pushed macrophages (immune cells) toward a more inflammatory M1 phenotype rather than the healing-promoting M2 phenotype. Treatment with an H₂S donor compound reduced inflammatory markers and decreased macrophage accumulation in joints, suggesting that H₂S therapy could potentially help manage the more severe inflammation seen in diabetic osteoarthritis patients, though this approach would need further development before clinical application.

METABOLIC SYNDROME AND OSTEOARTHRITIS: IMPLICATIONS FOR THE MANAGEMENT OF AN INCREASINGLY COMMON PHENOTYPE.

I apologize, but I cannot provide a meaningful summary of this research paper because the abstract is listed as "NA" (not available).

To write an accurate summary focusing on the study objective, key methods, findings regarding osteoarthritis phenotypes/subgroups, and implications for physiotherapy management, I would need access to the actual abstract content that describes the research methodology, results, and conclusions.

If you could provide the complete abstract, I would be happy to create a concise 3-4 sentence summary in plain language suitable for clinicians and researchers working in osteoarthritis phenotyping and musculoskeletal rehabilitation.

MESENCHYMAL PROGENITOR CELLS FROM NON-INFLAMED VERSUS INFLAMED SYNOVIUM POST-ACL INJURY PRESENT WITH DISTINCT PHENOTYPES AND CARTILAGE REGENERATION CAPACITY.

This study aimed to characterize mesenchymal progenitor cells (MPCs) from knee joint synovium in people with and without ACL injuries, focusing on their potential for cartilage repair. The researchers used proteomics analysis to identify distinct MPC subpopulations and tested their cartilage regeneration abilities through laboratory and animal studies.

The key finding was that synovial tissue contains multiple distinct MPC subgroups, with the abundance of these subpopulations changing after joint injury. Importantly, only specific MPC subgroups (identified by CD82 and CD59 surface markers) demonstrated strong cartilage repair capabilities in living tissue.

These results suggest that even injured joints retain populations of cells capable of cartilage regeneration, which could be targeted for future osteoarthritis treatments. For clinicians and physiotherapists, this research highlights the potential for developing personalized cell-based therapies and may inform rehabilitation strategies that could optimize the natural repair capacity of different patient subgroups following knee injuries.

SOCIOECONOMIC STATUS, MENTAL HEALTH, AND NUTRITION ARE THE PRINCIPAL TRAITS FOR LOW BACK PAIN PHENOTYPING: DATA FROM THE OSTEOARTHRITIS INITIATIVE.

This study aimed to identify distinct low back pain (LBP) phenotypes and key factors predicting chronicity using comprehensive data analysis from 215 individuals with LBP in the Osteoarthritis Initiative cohort. Researchers used unsupervised machine learning to analyze 1,190 variables and clustering techniques to identify phenotypes, then built predictive models to distinguish between acute and persistent LBP cases over 8 years of follow-up.

Three distinct LBP phenotypes emerged: a high socioeconomic status group with low pain severity, a low socioeconomic status group with high pain severity, and an intermediate group. Notably, socioeconomic status, mental health, and nutrition were the most influential clustering factors, while traditional biomedical markers like age, sex, and BMI showed little influence on phenotype classification.

These findings suggest that LBP management and physiotherapy should prioritize psychosocial factors and lifestyle interventions rather than focusing primarily on biomedical characteristics, potentially leading to more personalized and effective treatment approaches for different patient subgroups.

THE MIR-21-5P ENRICHED IN THE APOPTOTIC BODIES OF M2 MACROPHAGE-DERIVED EXTRACELLULAR VESICLES ALLEVIATES OSTEOARTHRITIS BY CHANGING MACROPHAGE PHENOTYPE.

This study investigated how apoptotic bodies (cellular debris from dying cells) from anti-inflammatory M2 macrophages could treat osteoarthritis by changing the balance of immune cell types in joints. The researchers used a mouse model of osteoarthritis and analyzed the effects of M2-derived apoptotic bodies on macrophage behavior, cartilage damage, and gait patterns through RNA sequencing and cellular uptake studies. Key findings showed that these apoptotic bodies contain high levels of miR-21-5p (a regulatory molecule) and can reprogram harmful pro-inflammatory M1 macrophages into beneficial anti-inflammatory M2 macrophages within 24 hours, leading to reduced cartilage damage and improved walking patterns in arthritic mice. This research suggests a potential new therapeutic approach for osteoarthritis treatment that could complement existing physiotherapy interventions by targeting the underlying inflammatory processes that drive joint degeneration, though clinical translation would require further development of delivery methods for this cell-based therapy.

EFFICACY AND SAFETY OF TOTAL GLUCOSIDES OF PAEONY IN THE TREATMENT OF 5 TYPES OF INFLAMMATORY ARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

This systematic review and meta-analysis evaluated the efficacy and safety of Total Glucosides of Paeony (TGP), a traditional Chinese medicine compound, across five different types of inflammatory arthritis. The researchers analyzed 63 randomized controlled trials involving 5,293 participants with rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, juvenile idiopathic arthritis, and psoriatic arthritis using standard meta-analysis methods.

The study found that TGP demonstrated condition-specific benefits across different arthritis phenotypes: it improved disease activity scores and reduced inflammatory markers (ESR, CRP, TNF-α, IL-6) in rheumatoid arthritis and ankylosing spondylitis, reduced pain scores and nitric oxide levels in osteoarthritis, and showed similar anti-inflammatory effects in juvenile idiopathic arthritis and psoriatic arthritis. Additionally, TGP appeared to have a good safety profile, with no increase in adverse events compared to standard treatments.

These findings suggest TGP could serve as a complementary therapeutic option for managing inflammation and symptoms across different inflammatory arthritis phenotypes, though the authors emphasize that larger, higher-quality trials are needed before definitive clinical recommendations can be made for physiotherapy and rheumatology practice.

DEXAMETHASONE LIPOSOMES ALLEVIATE OSTEOARTHRITIS IN MIR-204/-211-DEFICIENT MICE BY REPOLARIZING SYNOVIAL MACROPHAGES TO M2 PHENOTYPES.

This study investigated whether dexamethasone liposomes (DEX-LIPS) could treat osteoarthritis by targeting specific immune cell types in genetically modified mice. Researchers used mice lacking miR-204/-211 genes (which developed more severe arthritis) and induced osteoarthritis surgically, then treated them weekly with DEX-LIPS for 3 months while measuring pain, inflammation, joint damage, and immune cell activity. The key finding was that DEX-LIPS successfully reduced arthritis severity by reprogramming synovial macrophages from inflammatory (M1) to anti-inflammatory (M2) phenotypes, while also decreasing pain and inflammatory markers. These results suggest that targeted drug delivery systems that can shift macrophage populations toward anti-inflammatory states may offer a promising therapeutic approach for osteoarthritis management, potentially informing future treatments that focus on modulating local immune responses rather than just managing symptoms.

HYPOXIA PRECONDITIONED SERUM (HPS) PROMOTES PROLIFERATION AND CHONDROGENIC PHENOTYPE OF CHONDROCYTES IN VITRO.

This study investigated whether hypoxia preconditioned serum (HPS) could improve the maintenance of chondrogenic phenotype during in vitro expansion of chondrocytes for autologous chondrocyte implantation (ACI) procedures. The researchers analyzed growth factor concentrations in HPS versus normal serum and tested different HPS concentrations (10% and 40%) on human osteoarthritic chondrocytes, measuring proliferation and chondrogenic markers including collagen II, SOX9, and differentiation indices.

Key findings revealed that HPS contained higher concentrations of chondrogenic growth factors and that HPS-10% treatment produced the highest chondrogenic differentiation index (collagen II/collagen I ratio) and elevated SOX9 expression compared to conventional fetal calf serum or normal serum conditions. While higher HPS concentrations (40%) promoted greater cell proliferation, the lower concentration (10%) was optimal for maintaining the desired chondrogenic phenotype.

These results suggest that HPS-10% could enhance current ACI protocols by better preserving the cartilage-forming characteristics of chondrocytes during laboratory expansion, potentially improving clinical outcomes for patients with cartilage defects and osteoarthritis requiring cell-based therapies.

IDENTIFYING MULTIVARIATE DISEASE TRAJECTORIES AND POTENTIAL PHENOTYPES OF EARLY KNEE OSTEOARTHRITIS IN THE CHECK COHORT.

This study aimed to identify distinct knee osteoarthritis phenotypes by analyzing disease trajectories over 10 years in 1002 early-OA patients from the CHECK cohort. The researchers used functional data analysis to track changes in WOMAC scores (pain, function, stiffness) and radiographic features of both tibiofemoral and patellofemoral joints, then applied cluster analysis to group patients with similar trajectory patterns.

The analysis revealed multiple trajectory patterns: five for WOMAC symptoms (representing stable or changing symptom levels), eight for tibiofemoral features, and six for patellofemoral features. When combining these trajectories, six main phenotypes emerged based primarily on functional symptoms and patellofemoral radiographic changes, while tibiofemoral features contributed less to the clustering. Importantly, when baseline characteristics were included, sex and menopausal status became dominant factors in defining eight distinct phenotypes.

The findings suggest that knee OA phenotypes are characterized by relatively independent symptomatic and structural components, with patient demographics (particularly sex and menopause) being more influential than radiographic severity in defining subgroups. These phenotypes could potentially guide personalized treatment approaches and improve patient selection for targeted interventions, though validation studies are needed before clinical implementation.

EFFECTS OF LEPTIN AND BODY WEIGHT ON INFLAMMATION AND KNEE OSTEOARTHRITIS PHENOTYPES IN FEMALE RATS.

This study investigated whether leptin (a hormone linked to obesity) causes knee osteoarthritis independently of increased body weight in female rats. Researchers used two rat models: obese rats without leptin signaling compared to lean rats, and lean rats treated with leptin versus controls, then assessed cartilage damage, bone changes, and inflammatory markers over 23 weeks.

The study identified two distinct osteoarthritis phenotypes: obese rats (without leptin signaling) developed severe focal cartilage lesions and bone spurs primarily in the medial knee compartment, while lean rats treated with leptin showed milder but widespread cartilage deterioration and increased bone density. Leptin treatment also caused different inflammatory patterns, with reduced systemic inflammation but increased local joint inflammation compared to leptin-deficient obese rats.

These findings suggest that obesity-related osteoarthritis develops through both leptin-dependent and leptin-independent pathways, creating different disease patterns that may require tailored management approaches - potentially focusing on systemic metabolic factors for obese patients versus inflammatory control for those with elevated leptin levels.

IRON REGULATES CHONDROCYTE PHENOTYPE IN HAEMOPHILIC CARTILAGE THROUGH THE PTEN/PI3 K/AKT/FOXO1 PATHWAY.

This study investigated how iron overload damages cartilage in people with hemophilia by examining the cellular mechanisms that control cartilage cell behavior. The researchers compared cartilage samples from patients with hemophilic arthritis versus osteoarthritis using laboratory techniques, and tested iron effects on normal cartilage cells in culture.

The key finding revealed that hemophilic arthritis patients showed distinct molecular patterns compared to osteoarthritis patients, with iron exposure disrupting a specific cellular pathway (PTEN/PI3K/AKT/FOXO1) that controls cartilage cell function and survival. This iron-induced pathway disruption occurred in a dose-dependent manner, meaning higher iron levels caused greater cellular dysfunction.

These results identify hemophilic arthritis as having a different underlying disease mechanism than typical osteoarthritis, suggesting it represents a distinct cartilage destruction phenotype driven by iron accumulation. For clinical management, this implies that hemophilic arthritis may require specialized treatment approaches targeting iron-related damage rather than standard osteoarthritis interventions, potentially informing the development of iron-specific therapies or modified rehabilitation protocols for hemophilia patients.

THERAPEUTIC MODULATION OF CELL MORPHOLOGY AND PHENOTYPE OF DISEASED HUMAN CELLS TOWARDS A HEALTHIER CELL STATE USING LIGNIN.

This study investigated whether lignin (a natural plant compound) could therapeutically modify the shape and function of diseased cartilage cells from osteoarthritis patients. The researchers used automated cell imaging to measure cell shape changes and molecular techniques to assess gene expression in osteoarthritic chondrocytes treated with different lignin concentrations.

The key finding was that lignin treatment dose-dependently restored diseased cartilage cells toward a healthier, less fibroblast-like shape while simultaneously improving their molecular profile - reducing inflammatory markers (IL-6) and fibrosis genes (COL1A2) while increasing healthy cartilage matrix genes (COL2A1). This represents the first evidence that lignin can reverse both the physical appearance and functional characteristics of diseased cells.

These findings suggest lignin could offer a novel therapeutic approach for osteoarthritis management, potentially through topical applications, injectable treatments, or incorporation into regenerative medicine implants, though clinical translation and safety studies would be needed before implementation in physiotherapy or clinical practice.

TRENDS IN PREVALENCE AND IMPLANT TYPES IN THE NOVA SCOTIA JOINT DATABASE REGISTRY BETWEEN 2005 AND 2021.

This study analyzed trends in shoulder arthroplasty procedures using the Nova Scotia Joint Database Registry from 2005-2021, examining 1,545 patients to evaluate changes in surgical rates, indications, and implant types over time. The researchers reviewed registry data to identify procedure types, surgical indications, surgeon volumes, and revision rates across nearly two decades.

The study identified distinct patient subgroups based on surgical indication: degenerative osteoarthritis was the most common (58.1%), followed by acute proximal humerus fractures (15.1%) and rotator cuff arthropathy (14.2%), with total shoulder arthroplasty being the most frequent procedure (32.2%). A notable trend emerged showing increasing use of both total shoulder arthroplasties and reverse shoulder arthroplasties since 2016, with most procedures (84.1%) performed by two fellowship-trained specialists.

These findings suggest evolving surgical management patterns for different shoulder pathology phenotypes, with the increasing adoption of reverse shoulder arthroplasty likely reflecting expanded indications and improved outcomes for complex cases like rotator cuff arthropathy. For physiotherapy practice, understanding these distinct patient subgroups and their associated surgical approaches can inform more targeted pre- and post-operative rehabilitation protocols tailored to specific pathology types and expected functional outcomes.

[PERIODICITY ANALYSIS OF REINJECTION IN GONARTHROSIS WITH DIFFERENT TYPES OF HYALURONIC ACIDS].

I apologize, but I cannot provide a meaningful summary of this study as the abstract is listed as "NA" (not available).

Based solely on the title, this appears to be a study examining the timing patterns of repeat hyaluronic acid injections in knee osteoarthritis (gonarthrosis) patients, comparing different types of hyaluronic acid preparations. However, without the abstract containing the study methods, results, and conclusions, I cannot accurately describe the study objective, methodology, findings about patient subgroups or phenotypes, or clinical implications for physiotherapy management.

To provide the comprehensive summary you've requested, I would need access to the complete abstract or additional study details.

ANABOLIC PHENOTYPE IN CARTILAGE-SPECIFIC MITOGEN-INDUCIBLE GENE-6 KNOCKOUT MICE IS INDEPENDENT OF TRANSFORMING GROWTH FACTOR-Α.

This study investigated whether blocking TGF-α could prevent the cartilage overgrowth seen in mice lacking the MIG-6 gene, which normally regulates cartilage development. The researchers created double knockout mice (missing both MIG-6 and TGF-α genes) and compared cartilage thickness, cell density, and bone nodule formation in knee and elbow joints at 12 weeks using histological analysis and immunostaining.

The key finding was that mice without MIG-6 still developed thickened cartilage and abnormal bone-cartilage nodules even when TGF-α was also removed, indicating this "anabolic phenotype" (excessive cartilage growth) occurs through pathways independent of TGF-α. Both single MIG-6 knockout and double knockout mice showed increased cartilage cell density and elevated markers of cartilage activity (SOX9, phospho-EGFR) compared to controls.

These results suggest that targeting TGF-α alone may not be sufficient to control cartilage overgrowth in osteoarthritis, as alternative growth pathways appear to compensate, highlighting the need to identify other therapeutic targets for managing cartilage metabolism in joint diseases.

MACHINE LEARNING APPROACHES TO THE PREDICTION OF OSTEOARTHRITIS PHENOTYPES AND OUTCOMES.

This review examines how artificial intelligence and machine learning (AI/ML) methods can be applied to osteoarthritis research to better understand disease complexity and improve clinical decision-making. The authors systematically reviewed recent implementations of AI/ML approaches that analyze multidimensional, multi-source data to predict OA incidence and progression, identify distinct disease phenotypes, and discover new biomarkers. Key findings indicate that these computational methods can successfully identify different OA subgroups and predict disease outcomes by integrating diverse data sources, providing machine-learned evidence to support clinical decisions. The implications for management include the potential for personalized treatment approaches and improved disease prevention strategies, though the authors emphasize the need for clinicians and researchers to understand both the strengths and limitations of these AI/ML methods in OA applications.

DEEP LEARNING BASED PHENOTYPING OF MEDICAL IMAGES IMPROVES POWER FOR GENE DISCOVERY OF COMPLEX DISEASE.

This study aimed to improve knee osteoarthritis (OA) phenotyping using deep learning analysis of medical images to enhance genetic discovery studies. The researchers developed two deep learning models: one to identify OA cases from knee DXA scans and another to measure joint space width as a quantitative marker of disease severity. The image-based phenotyping identified 178% more OA cases than electronic health records alone, with these additional cases showing higher rates of knee pain and longer symptom duration, while the quantitative joint space measurements improved genetic association discovery by an order of magnitude compared to simple case-control classification. These findings suggest that automated image analysis could significantly improve OA diagnosis and subtyping in clinical practice, potentially enabling earlier identification of patients who would benefit from physiotherapy interventions and revealing important associations like increased fracture risk that aren't captured in routine medical records.

BIOMARKERS FOR OSTEOARTHRITIS: CURRENT STATUS AND FUTURE PROSPECTS.

This review examines the current status and future potential of biomarkers in osteoarthritis research and clinical practice. The authors conducted a comprehensive review of biomarker research, focusing particularly on soluble biomarkers and their applications in clinical trials and patient care. Key findings indicate that while soluble biomarkers are not yet ready for routine clinical use, they show significant promise for identifying distinct OA phenotypes and subtypes, enabling better patient stratification and more precise treatment approaches. The implications suggest that biomarkers could revolutionize OA management by facilitating personalized medicine approaches, improving clinical trial design through better patient selection, and serving as surrogate endpoints to accelerate drug development - ultimately leading to more targeted and effective treatments for different OA subgroups.

DISRUPTION OF COL9A2 EXPRESSION LEADS TO DEFECTS IN OSTEOCHONDRAL HOMEOSTASIS AND OSTEOARTHRITIS-LIKE PHENOTYPE IN MICE.

This study investigated how COL9A2 gene deficiency contributes to knee osteoarthritis development by examining COL9A2-deficient mice using multiple imaging and biochemical techniques including micro-CT, biomechanical testing, and histological analysis. The researchers identified two distinct phenotypic stages: early-stage changes characterized by sparse, deformed subchondral bone with reduced load-bearing capacity and disrupted bone metabolism, followed by late-stage severe cartilage degeneration with marked thickness reduction and destruction. The findings reveal that COL9A2 deficiency creates a progression where initial subchondral bone weakness leads to excessive mechanical loading on cartilage, ultimately causing osteoarthritis-like joint damage. These results suggest that osteoarthritis phenotyping should consider subchondral bone integrity as a primary factor, and physiotherapy interventions may need to be tailored based on disease stage—focusing on bone health preservation early and joint protection strategies later to prevent excessive cartilage loading.

CIRCRREB1 MEDIATES LIPID METABOLISM RELATED SENESCENT PHENOTYPES IN CHONDROCYTES THROUGH FASN POST-TRANSLATIONAL MODIFICATIONS.

This study aimed to investigate how circRREB1, a circular RNA molecule, contributes to age-related osteoarthritis by affecting cellular aging (senescence) in cartilage cells. The researchers used laboratory experiments with chondrocytes (cartilage cells) and mouse models to examine how circRREB1 influences lipid metabolism and cellular signaling pathways, including testing the effects of reducing circRREB1 levels through genetic manipulation and viral injections.

The key finding was that circRREB1 promotes harmful age-related changes in cartilage by stabilizing a protein called FASN, which disrupts normal cellular signaling and leads to increased cellular senescence and osteoarthritis progression. When circRREB1 was reduced or blocked, the researchers observed decreased cellular aging markers and protection against osteoarthritis development in their experimental models.

These findings suggest that circRREB1 could serve as both a biomarker to identify patients with age-related osteoarthritis phenotypes and a potential therapeutic target, though clinical translation and relevance to current physiotherapy approaches remains to be established.

OXIDATIVE STRESS MEDIATES ASSOCIATIONS BETWEEN PREOPERATIVE PSYCHOSOCIAL PHENOTYPE AND PAIN-RELATED OUTCOMES AT 6 MONTHS FOLLOWING TOTAL KNEE ARTHROPLASTY: A LONGITUDINAL COHORT STUDY.

This longitudinal cohort study investigated whether oxidative stress mediates the relationship between preoperative psychological factors and poor pain outcomes following total knee arthroplasty (TKA) in 91 osteoarthritis patients. The researchers measured depression, anxiety, pain catastrophizing, and central sensitization markers before surgery, quantified oxidative stress biomarkers during surgery, and assessed pain and function at 6 months post-TKA.

The study identified distinct phenotypic pathways: patients with higher preoperative depression, anxiety, and catastrophizing showed elevated oxidative stress levels, which in turn predicted worse 6-month pain and functional outcomes, while central sensitization markers (widespread pain, temporal summation) directly affected outcomes independent of oxidative stress mechanisms. Key findings revealed that oxidative stress significantly mediated the negative effects of psychological factors on post-surgical outcomes, particularly for depression and catastrophizing.

These results suggest that osteoarthritis patients can be phenotyped based on whether their risk for poor TKA outcomes stems from psychological factors (mediated through oxidative stress) versus central sensitization mechanisms. This phenotyping approach could inform targeted preoperative interventions, with psychological therapies and anti-oxidative treatments potentially benefiting the psychosocial phenotype, while central sensitization-focused treatments may be more appropriate for patients with widespread pain patterns.

IMPACT OF HAND OSTEOARTHRITIS IN WOMEN ON MAXIMAL FORCES IN SIX DIFFERENT GRASP TYPES.

This study aimed to compare maximal hand force across six different grasp types between healthy individuals and women with hand osteoarthritis (HOA), and to identify which grasp types could best detect HOA. The researchers tested 33 healthy participants and 30 women with HOA using standardized force measurements across six grasp patterns, analyzing the data with statistical methods including discriminant analysis to identify HOA predictors.

The key finding was that women with HOA showed significantly reduced force (p < 0.001) across all six grasp types compared to healthy women, indicating widespread functional impairment beyond traditional grip strength measures. Notably, the oblique grasp emerged as the most discriminating test, achieving 88.2% specificity and 83.3% sensitivity for detecting HOA, suggesting this specific movement pattern may be particularly affected by the condition.

These findings suggest that comprehensive grip strength assessment using multiple grasp types could enhance HOA detection and monitoring, with the oblique grasp potentially serving as a simple, non-invasive screening tool for clinicians and a targeted outcome measure for physiotherapy interventions.

MESENCHYMAL STEM CELLS IN SYNOVIAL FLUID INCREASE IN NUMBER IN RESPONSE TO SYNOVITIS AND DISPLAY MORE TISSUE-REPARATIVE PHENOTYPES IN OSTEOARTHRITIS.

This study investigated how synovial fluid mesenchymal stem cells (SF-MSCs) respond to joint damage and inflammation in osteoarthritis, aiming to understand their potential role in tissue repair. The researchers used a rat model with partial meniscectomy to induce osteoarthritis, then analyzed SF-MSC numbers, colony formation, and gene expression patterns at 2, 4, and 6 weeks post-surgery compared to intact and sham-operated joints.

The key finding was that SF-MSC numbers increased significantly in response to joint damage, with the strongest correlation observed between cell numbers and synovitis severity (r=0.583) rather than other structural changes. Gene expression analysis revealed that SF-MSCs from osteoarthritic joints displayed enhanced tissue-reparative characteristics, including upregulated genes related to extracellular matrix binding, TGF-β signaling, and antioxidant activity.

These findings suggest that the synovial environment naturally mobilizes reparative stem cells in response to inflammation and tissue damage, indicating that therapeutic strategies targeting synovitis management and supporting endogenous SF-MSC function could be promising approaches for osteoarthritis treatment and rehabilitation.

THE MATSUDAI KNEE OSTEOARTHRITIS SURVEY SHOWED THE LONGITUDINAL CHANGES OF KNEE PHENOTYPES IN ALIGNMENT AND STRUCTURE DURING 23-28 YEARS.

This long-term study followed 285 healthy female knees over 23-28 years to understand how knee structure and alignment change as osteoarthritis develops, comparing those who remained healthy with those who developed early or advanced OA. Using standing X-rays, researchers measured knee alignment, joint line parameters, and cortical bone thickness at baseline and follow-up to track structural changes and identify different knee phenotypes. The study found that knees developing OA showed significant shifts toward varus (inward) alignment and changes in tibial and femoral joint line measurements, while all groups experienced decreased cortical bone thickness with altered distribution patterns over time. These findings suggest that baseline alignment and tibial structural features can help predict OA development, potentially allowing clinicians and physiotherapists to identify at-risk individuals earlier and develop targeted interventions to address specific phenotypic patterns before advanced joint damage occurs.

WHICH KNEE PHENOTYPES EXHIBIT THE STRONGEST CORRELATION WITH CARTILAGE DEGENERATION?

This study aimed to identify which knee alignment phenotypes show the strongest correlation with cartilage degeneration patterns in moderate to advanced osteoarthritis. The researchers analyzed 466 knees from patients aged 45-79 years, categorizing them into 25 different phenotypes based on femoral and tibial alignment angles from full-limb radiographs, and tracked cartilage changes using quantitative MRI measurements over 24-48 months.

The key finding was that two specific phenotypes showed particularly rapid cartilage deterioration: valgus femur with valgus tibia (associated with cartilage loss in medial and lateral tibial regions), and valgus femur with varus tibia (linked to anterior lateral tibial cartilage loss). Importantly, these alignment patterns produced atypical cartilage damage patterns that didn't follow the expected medial versus lateral compartment distribution typically seen with simple varus or valgus malalignment.

These findings suggest that current approaches to osteoarthritis management may need to be more individualized based on specific alignment phenotypes rather than simple varus/valgus classifications. For clinicians and physiotherapists, this research highlights the importance of detailed alignment assessment when planning interventions, as certain phenotypes may require targeted strategies to address unexpected patterns of cartilage deterioration.

EXPLORING DIFFERENT MODELS OF PAIN PHENOTYPES AND THEIR ASSOCIATION WITH PAIN WORSENING IN PEOPLE WITH EARLY KNEE OSTEOARTHRITIS: THE MOST COHORT STUDY.

This study aimed to identify pain phenotypes in people with early-stage knee osteoarthritis and determine whether these phenotypes predicted pain worsening over two years. Using latent class analysis, researchers examined two models: Model A included pain sensitivity measures, psychological factors, and sleep quality in 750 participants, while Model B added physical factors like gait, muscle strength, and imaging findings in 333 participants. Both models successfully identified distinct phenotypes, with the most severe phenotype characterized by psychological factors, widespread pain, and nervous system sensitization, plus physical impairments in the expanded model. Surprisingly, none of the identified phenotypes significantly predicted pain worsening at two years, suggesting that while distinct pain phenotypes exist in early knee osteoarthritis, they may not be useful for predicting short-term pain progression or guiding targeted physiotherapy interventions based on phenotype alone.

METABOLIC PHENOTYPES REFLECT PATIENT SEX AND INJURY STATUS: A CROSS-SECTIONAL ANALYSIS OF HUMAN SYNOVIAL FLUID.

This study aimed to identify distinct metabolic phenotypes in synovial fluid based on patient sex and knee injury type to better understand post-traumatic osteoarthritis (PTOA) development. Researchers analyzed synovial fluid from 33 knee arthroscopy patients (ages 18-70) using liquid chromatography-mass spectrometry to compare metabolic profiles across different injury types (ligament, meniscal, or combined injuries) and between male and female patients.

The analysis revealed that different knee injuries produced unique alterations in synovial fluid metabolites affecting amino acid, lipid, and inflammatory pathways, with notable sex-based differences in metabolite concentrations (such as cervonyl carnitine). These findings suggest that injury type and patient sex create distinct metabolic phenotypes that may influence endogenous repair mechanisms differently between males and females.

For clinical management, this research supports the need for personalized approaches to PTOA prevention and treatment based on both injury type and patient sex, potentially informing targeted physiotherapy interventions and monitoring strategies as the field moves toward precision medicine in musculoskeletal care.

A HIGHER SKELETAL MUSCLE MASS AND LOWER ADIPOSITY PHENOTYPE IS ASSOCIATED WITH BETTER CARDIOMETABOLIC CONTROL IN ADULTS WITH HIP AND KNEE OSTEOARTHRITIS: RESULTS FROM THE CHILEAN NATIONAL HEALTH SURVEY 2016-2017.

This study aimed to examine how different body composition patterns (muscle mass and fat distribution) affect heart and metabolic health in adults with hip and knee osteoarthritis using data from 4,996 Chilean adults. Researchers classified participants into four groups based on skeletal muscle mass and waist circumference, then compared cardiovascular and metabolic outcomes between those with and without osteoarthritis in each group.

The key finding was that people with osteoarthritis who had low muscle mass combined with high abdominal fat showed the worst cardiovascular profile, particularly elevated blood pressure (up to 18 mmHg higher in hip osteoarthritis). Adults with osteoarthritis had more than double the risk of diabetes and hypertension, nearly 5 times higher risk of metabolic syndrome, and over double the cardiovascular disease risk compared to those without osteoarthritis.

These results suggest that osteoarthritis patients should be assessed and managed not just for joint symptoms, but as part of a broader cardiometabolic health approach. For physiotherapists and clinicians, this emphasizes the importance of exercise programs that preserve muscle mass and reduce abdominal fat, alongside nutritional interventions, as essential components of comprehensive osteoarthritis care.

MECHANISTIC PROSPECTIVE AND PHARMACOLOGICAL ATTRIBUTES OF QUERCETIN IN ATTENUATION OF DIFFERENT TYPES OF ARTHRITIS.

This review examined the therapeutic potential of quercetin, a natural flavonoid compound, for treating different types of arthritis including rheumatoid arthritis (RA), osteoarthritis (OA), gouty arthritis, and psoriatic arthritis. The authors analyzed existing research on quercetin's anti-inflammatory mechanisms, focusing on how it regulates key inflammatory pathways such as NF-κB, MAK, and WNT/β-catenin that are involved in arthritis progression. The review found that quercetin shows promise for managing various arthritis phenotypes due to its ability to target multiple inflammatory pathways simultaneously, though its therapeutic application is currently limited by poor bioavailability in the body. For clinical practice, this suggests that while quercetin-based treatments could potentially offer a natural therapeutic approach for arthritis management, further development of drug delivery systems is needed to improve its effectiveness before it can be integrated into standard physiotherapy or medical care protocols.

CARTILAGE TISSUE FROM SITES OF WEIGHT BEARING IN PATIENTS WITH OSTEOARTHRITIS EXHIBITS A DIFFERENTIAL PHENOTYPE WITH DISTINCT CHONDROCYTES SUBESTS.

This study aimed to identify distinct chondrocyte subpopulations in osteoarthritic cartilage and understand how mechanical loading influences their characteristics. The researchers used proteomic analysis and single-cell RNA sequencing to compare cartilage from weight-bearing versus non-weight-bearing regions in OA patients, combined with cell culture studies and immunofluorescence validation.

The key finding was the identification of a specific chondrocyte subset called OA hypertrophic chondrocytes (OAHCs) that are uniquely present in weight-bearing areas of damaged cartilage. These OAHCs express distinct marker genes (SLC39A14 and COL10A1), are primarily located in superficial cartilage layers, and show active cellular communication through TGFβ signaling pathways, along with altered iron metabolism when stimulated.

These findings suggest that mechanical loading creates distinct cellular environments in OA joints, with specific chondrocyte phenotypes emerging in high-stress areas. This has important implications for physiotherapy and rehabilitation, as it provides evidence that load management strategies may need to consider these regional cellular differences, and opens potential for targeted therapies focusing on these specific cell populations to slow OA progression.

KNEES WITH ANTEROMEDIAL OSTEOARTHRITIS SHOW A SUBSTANTIAL PHENOTYPIC VARIATION PRIOR AND FOLLOWING MEDIAL UNICOMPARTMENTAL KNEE ARTHROPLASTY.

This study aimed to evaluate the phenotypic variation in knee alignment among 1000 patients with anteromedial osteoarthritis before and after medial unicompartmental knee arthroplasty (UKA) using the Coronal Plane Alignment of the Knee (CPAK) classification system. The researchers analyzed knee alignment patterns by categorizing patients into nine distinct CPAK phenotypes based on their hip-knee-ankle angle and joint line obliquity, examining differences by sex and age, and tracking how these phenotypes changed following surgery.

The study revealed substantial phenotypic variation, with CPAK phenotype I being most common before surgery (45.0%) and phenotype II most prevalent after surgery (53.3%), and notable sex differences in phenotype distribution. Only 45.1% of knees maintained their preoperative alignment phenotype after UKA, with phenotypes II and III showing the highest stability (67.7% and 65.8% respectively).

These findings challenge the assumption that knees with identical anteromedial OA wear patterns have uniform characteristics, highlighting the complexity and variability within this OA subtype, which has important implications for personalized surgical planning and potentially for developing more targeted physiotherapy and rehabilitation approaches based on individual alignment phenotypes.

BILATERAL KNEE OSTEOARTHRITIS TREATED WITH MEDIAL OPEN-WEDGE HIGH TIBIAL OSTEOTOMY USING TWO TYPES OF Β-TRICALCIUM PHOSPHATE WITH DIFFERING PLACEMENTS IN EACH KNEE: A REPORT OF TWO CASES.

This case report examined bone remodeling patterns and clinical outcomes in two patients who underwent medial open-wedge high tibial osteotomy (MOWHTO) for bilateral knee osteoarthritis, using different synthetic bone graft materials in each knee. The researchers compared two types of β-tricalcium phosphate (β-TCP) - unidirectional porous (UDPTCP) and spherical porous (SPTCP) - placed in different anterior-posterior positions, and evaluated bone remodeling using CT scans immediately post-surgery and at one year follow-up. The key finding was that UDPTCP consistently showed faster bone remodeling compared to SPTCP, regardless of whether it was placed anteriorly or posteriorly in the osteotomy gap. Both materials provided equivalent clinical outcomes with no correction loss, suggesting that while bone incorporation rates differ between β-TCP types, both are viable options for MOWHTO procedures, potentially giving surgeons flexibility in material selection based on availability or patient-specific factors.

INDIVIDUAL PHENOTYPE DOES NOT IMPACT THE OUTCOME OF MECHANICAL ALIGNED TOTAL KNEE ARTHROPLASTIES FOR VALGUS OSTEOARTHRITIS.

This study investigated whether individual knee alignment patterns (phenotypes) affect outcomes after mechanically aligned total knee arthroplasty (TKA) in patients with valgus osteoarthritis. Researchers retrospectively analyzed 158 knees, measuring alignment angles on X-rays and grouping knees using the CPAK (Coronal Plane Alignment of the Knee) classification system, then assessed patient outcomes using standardized measures including WOMAC, UCLA activity scores, and quality of life measures.

The key finding was that different knee phenotypes did not significantly impact TKA outcomes when mechanical alignment was used, suggesting this traditional alignment approach works well across various natural knee shapes in valgus arthritis. However, knees that remained in valgus alignment after surgery showed worse activity levels and quality of life improvements compared to those achieving neutral mechanical alignment.

These results support using mechanical alignment as the target for TKA in valgus osteoarthritis regardless of the patient's natural knee phenotype, which simplifies surgical decision-making and suggests that individualizing alignment based on phenotype may not be necessary for this patient group.

ALIGNMENT STRATEGY FOR DIFFERENT TYPES OF VARUS KNEE WITH GENERIC INSTRUMENTS: MECHANICAL ALIGNMENT OR KINEMATIC ALIGNMENT?

This study aimed to compare mechanical alignment (MA) versus kinematic alignment (KA) techniques in total knee arthroplasty for patients with different types of varus knee deformity using generic instruments. Researchers followed 127 patients for 12 months, categorizing them into Type I (n=64) and Type IV (n=63) varus knees based on the modified coronal plane alignment of the knee (MCPAK) classification, with each type further divided into MA and KA treatment groups.

The kinematic alignment approach demonstrated superior outcomes compared to mechanical alignment, showing significantly better pain relief and range of motion at 6 weeks post-surgery, consistently higher knee function scores (KOOS JR) at all follow-up points (6 weeks, 6 months, and 1 year), and improved patient satisfaction (forgotten joint scores) at 1 year. These findings suggest that kinematic alignment may be the preferred surgical approach for patients with MCPAK Type I and IV varus knee deformities, potentially leading to faster recovery and better long-term functional outcomes in total knee arthroplasty.

THE EFFICACY OF PLATELET-RICH PLASMA IN TREATING OSTEOARTHRITIS WITH AN INFLAMMATORY PHENOTYPE: A 5-YEAR FOLLOW UP RETROSPECTIVE STUDY.

This 5-year retrospective cohort study investigated whether platelet-rich plasma (PRP) injections are more effective in patients with inflammatory phenotype knee osteoarthritis (I-KOA) compared to conventional osteoarthritis. The researchers compared 211 I-KOA patients (identified through MRI findings) with 209 conventional KOA patients, with both groups receiving intensive PRP treatment (3 injections annually for 5 years, totaling 15 injections per patient).

While structural disease progression was similar between groups (no difference in joint space narrowing or Kellgren-Lawrence grades), patients with inflammatory phenotype osteoarthritis showed significantly better clinical outcomes, including lower rates of total knee replacement, delayed timing to surgery, and superior pain and function scores on standardized measures. These findings suggest that phenotyping osteoarthritis patients may help identify those most likely to benefit from PRP therapy, with inflammatory phenotype patients being particularly responsive to this treatment approach for symptom management, even though structural progression continues unchanged.

PHENOTYPE AND ENERGY METABOLISM DIFFER BETWEEN OSTEOARTHRITIC CHONDROCYTES FROM MALE COMPARED TO FEMALE PATIENTS: IMPLICATIONS FOR SEXUAL DIMORPHISM IN OSTEOARTHRITIS DEVELOPMENT?

This study investigated whether biological differences exist in osteoarthritic (OA) cartilage cells between male and female patients, given that knee OA is more common and severe in women. The researchers analyzed cartilage cells from knee replacement surgeries, comparing gene expression, protein production, and energy metabolism patterns between sexes, and used gene knockdown techniques to test the functional importance of key differences. The findings revealed distinct sex-based phenotypes: male OA chondrocytes showed higher levels of SOX9 (a cartilage-specific transcription factor), greater collagen production, and preferential use of glucose through glycolysis, while female chondrocytes had higher PGC1α levels, consumed more fats, and relied more on oxidative metabolism for energy. These fundamental biological differences suggest that OA may develop through different mechanisms in men versus women, indicating that sex-specific approaches to understanding OA pathogenesis and developing treatments, including physiotherapy interventions, may be necessary for optimal patient management.

ARTHRITIS FOUNDATION/HSS WORKSHOP ON HIP OSTEOARTHRITIS, PART 4: NONOPERATIVE OPTIONS, MACHINE LEARNING IN PREDICTING TOTAL HIP ARTHROPLASTY, ROBOTICS, AND PHENOTYPING TO GUIDE PRECISION REHABILITATION.

This paper reports on an expert workshop convened by the Arthritis Foundation and Hospital for Special Surgery to address the research gap in hip osteoarthritis compared to knee osteoarthritis. The workshop brought together thought leaders to review current approaches to late-stage hip osteoarthritis, covering conservative treatments, surgical decision-making, robotic advancements, and phenotyping strategies. Key discussions focused on the potential for phenotyping patients to guide precision rehabilitation approaches following total hip arthroplasty (THA). The workshop's recommendations highlight the need for personalized treatment strategies based on patient phenotypes, which could improve rehabilitation outcomes and optimize recovery pathways for individuals undergoing hip replacement surgery.

MUSCLE INFLAMMATION SUSCEPTIBILITY: A POTENTIAL PHENOTYPE FOR GUIDING PRECISION REHABILITATION AFTER TOTAL HIP ARTHROPLASTY IN END-STAGE OSTEOARTHRITIS.

This review introduces "Muscle Inflammation Susceptibility" (MUIS) as a distinct phenotype characterizing localized periarticular muscle inflammation present at the time of total hip arthroplasty (THA) in end-stage osteoarthritis patients. The authors propose that MUIS, which differs from systemic inflammation, contributes to muscle atrophy, poor muscle quality through fibrosis, and creates a challenging microenvironment that impairs muscle regeneration capacity. The phenotype is associated with reduced functional recovery outcomes following THA surgery. The authors suggest that identifying and understanding MUIS could guide precision rehabilitation approaches, allowing clinicians to tailor post-surgical treatment strategies based on individual patients' muscle inflammation profiles to optimize THA outcomes.

BIOPRINTING OF SCALED-UP MENISCAL GRAFTS BY SPATIALLY PATTERNING PHENOTYPICALLY DISTINCT MENISCUS PROGENITOR CELLS WITHIN MELT ELECTROWRITTEN SCAFFOLDS.

This study aimed to develop bioprinted meniscal grafts that better replicate the complex structure of native meniscus tissue by using zone-specific progenitor cells and advanced 3D printing techniques. The researchers used meniscus progenitor cells (MPCs) isolated from inner and outer meniscal zones, deposited them into melt electrowritten (MEW) scaffolds with elongated pore shapes, and developed an iterative printing process to create wedge-shaped constructs matching native meniscus geometry.

The key finding was that inner and outer zone MPCs maintained distinct phenotypic characteristics and produced different tissue compositions when spatially organized within the bioprinted constructs, successfully mimicking the zonal variations found in native meniscus tissue. The elongated scaffold pores effectively guided cell alignment and collagen organization, creating anisotropic fibrocartilaginous tissue with preferentially aligned networks.

These results demonstrate significant potential for creating more anatomically accurate meniscal replacements that could better restore joint function following meniscus injury. For clinical practice, this technology could eventually provide superior treatment options for meniscus tears, potentially reducing the long-term risk of osteoarthritis development compared to current surgical approaches.

SUSTAINED LIMB-LEVEL LOADING: A GROUND REACTION FORCE PHENOTYPE COMMON TO INDIVIDUALS AT HIGH RISK FOR AND THOSE WITH KNEE OSTEOARTHRITIS.

This study compared ground reaction force (GRF) patterns during walking between individuals 6-12 months after ACL reconstruction (ACLR) and both uninjured controls and people with varying severities of knee osteoarthritis. Using functional linear modeling in 196 participants, researchers analyzed vertical, anterior-posterior, and medial-lateral forces throughout the stance phase of gait. The key finding revealed that ACLR patients showed remarkably similar GRF profiles to those with mild knee osteoarthritis (KL grade 2), characterized by reduced loading forces during early and late stance phases compared to healthy controls, with greater similarities to more severe osteoarthritis as disease progressed. These findings suggest that ACLR patients and those with mild osteoarthritis share a common "sustained limb-level loading" phenotype, indicating both groups may benefit from similar targeted rehabilitation interventions focused on restoring normal loading patterns during walking.

IDENTIFIED SENESCENCE ENDOTYPES IN AGED CARTILAGE ARE REFLECTED IN THE BLOOD METABOLOME.

This study aimed to identify distinct cellular aging patterns (endotypes) in aged joint cartilage and determine whether these patterns could be detected through blood tests as potential biomarkers for osteoarthritis management. The researchers analyzed gene expression data from 57 cartilage samples using 131 aging-related genes and performed metabolic profiling on corresponding blood samples from 21 participants.

Two distinct aging endotypes were identified: Endotype-1 was characterized by abnormal cell growth pathways and specific proteins (FOXO4, RBL2, CDKN1B), while Endotype-2 showed increased inflammation with elevated levels of inflammatory markers (IL6, MMP1/3, VEGFC). Importantly, each cartilage endotype had corresponding metabolic signatures detectable in blood samples, suggesting these patterns could be identified through simple blood tests.

These findings suggest that osteoarthritis patients could be classified into distinct subgroups based on their underlying cellular aging patterns, potentially allowing for personalized treatment approaches—targeting cell cycle regulation for Endotype-1 patients and inflammation pathways for Endotype-2 patients, with blood-based biomarkers enabling non-invasive patient stratification.

A PHENOTYPIC SCREENING PLATFORM FOR CHRONIC PAIN THERAPEUTICS USING ALL-OPTICAL ELECTROPHYSIOLOGY.

This study aimed to develop a high-throughput laboratory platform for discovering new chronic pain treatments by modeling osteoarthritis (OA) pain using sensory neurons exposed to inflammatory substances found in arthritic joints. The researchers used an innovative optical system to simultaneously record electrical activity from hundreds of thousands of individual neurons, then screened approximately 3,000 existing drugs to identify compounds that could reverse pain-related changes in neural firing patterns. The screening revealed several categories of potential pain-relieving drugs, including ion channel blockers and notably, compounds targeting the RAF-MEK-ERK cellular signaling pathway, suggesting this pathway may be a key mechanism by which joint inflammation leads to chronic pain in OA patients. These findings provide new therapeutic targets for OA pain management and offer a powerful research tool that could accelerate the development of more effective pain medications for patients who currently have limited treatment options.

UNSUPERVISED DOMAIN ADAPTATION FOR AUTOMATED KNEE OSTEOARTHRITIS PHENOTYPE CLASSIFICATION.

This study aimed to develop an automated system for classifying knee osteoarthritis (OA) phenotypes using unsupervised domain adaptation (UDA) to overcome limitations when working with small, locally-collected MRI datasets. The researchers used a four-step machine learning pipeline that first trained a convolutional neural network on a large source dataset (318-960 MRI scans from the Osteoarthritis Initiative), then adapted it to work on a smaller target dataset (50 local MRI scans) to classify two OA phenotypes: cartilage/meniscus damage and subchondral bone changes.

The UDA approach significantly outperformed other methods, achieving excellent classification performance for cartilage/meniscus phenotypes (AUROC = 0.90) and good performance for subchondral bone phenotypes (AUROC = 0.75), compared to models that showed poor performance when trained only on the small local dataset. This technique has important implications for clinical practice and research, as it enables healthcare centers with limited patient data to accurately classify OA phenotypes automatically, potentially improving diagnostic consistency and enabling more personalized treatment approaches in musculoskeletal rehabilitation.

CD39+CD55- FB SUBSET EXHIBITS MYOFIBROBLAST-LIKE PHENOTYPE AND IS ASSOCIATED WITH PAIN IN OSTEOARTHRITIS OF THE KNEE.

This study aimed to identify and characterize specific fibroblast subgroups in knee osteoarthritis (OA) synovium and examine their relationship with pain symptoms. The researchers used flow cytometry to isolate fibroblast subsets based on CD39 and CD55 surface markers from 25 knee OA patients, then analyzed their gene and protein expression patterns using RNA sequencing and mass spectrometry.

The study identified two distinct fibroblast phenotypes: CD39+CD55- fibroblasts exhibited myofibroblast-like characteristics with high expression of muscle-related genes and pain-associated signaling pathways, while CD39-CD55+ fibroblasts showed more pro-inflammatory features and expressed lubricating proteins like PRG4. Importantly, patients with higher proportions of CD39+CD55- myofibroblast-like cells in their synovium experienced significantly more pain (both at rest and during activity), but this subset was not related to structural joint damage.

These findings suggest that synovial fibroblast subtypes may serve as biomarkers for pain-dominant OA phenotypes, potentially guiding personalized treatment approaches that target myofibroblast-related pain mechanisms rather than focusing solely on structural changes visible on imaging.

INFLAMMATORY AND METABOLIC SIGNALING INTERFACES OF THE HYPERTROPHIC AND SENESCENT CHONDROCYTE PHENOTYPES ASSOCIATED WITH OSTEOARTHRITIS.

This review study aimed to characterize the inflammatory and metabolic pathways underlying two key chondrocyte phenotypes in osteoarthritis (OA): hypertrophic and senescent cells. The authors analyzed existing literature on the molecular signatures and signaling mechanisms that drive cartilage cell transformation in OA joints.

The study identified that OA chondrocytes undergo distinct phenotypic changes - hypertrophic cells lose cartilage-protective markers (SOX-9, collagen II) while gaining inflammatory and degradative markers (RUNX2, MMP-13), eventually progressing to senescent cells that secrete harmful inflammatory substances. Key regulatory pathways including NF-κB, altered glucose metabolism, and cellular surveillance systems (YAP/TAZ, SIRT1) were found to control this pathological transformation.

The findings suggest that targeting senescent chondrocytes with senolytic agents (like dendrobin) could restore healthy cartilage production and reduce joint destruction, offering a promising therapeutic approach for OA management that goes beyond current symptom-focused treatments.

OSTEOARTHRITIS PAIN PHENOTYPES: HOW BEST TO CUT THE CAKE?

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SYNOVIAL INFLAMMATION IN OSTEOARTHRITIS. A TREATABLE TARGET?

This review examined why anti-inflammatory drugs targeting specific cytokines have failed in osteoarthritis (OA) trials, despite evidence that synovial inflammation contributes to pain and joint damage. The authors analyzed nine randomized clinical trials targeting IL-1 and TNFα that showed no benefit for short-term pain relief as their primary endpoints. The key finding is that current research lacks proper classification criteria to identify patients with inflammatory OA phenotypes and insufficient understanding of the synovitis-driven disease subtype, making it difficult to select appropriate patients for anti-inflammatory treatments. The implications suggest that clinicians and researchers need better phenotyping tools to identify inflammatory OA subgroups, should consider investigating alternative inflammatory mediators beyond IL-1 and TNFα, and may need longer-term studies (at least one year) to assess both pain relief and disease modification rather than focusing solely on short-term pain outcomes.

APPLICATION OF HUMAN PLATELET LYSATE IN CHONDROCYTE EXPANSION PROMOTES CHONDROGENIC PHENOTYPE AND SLOWS SENESCENCE PROGRESSION VIA BMP-TAK1-P38 PATHWAY.

This study investigated whether human platelet lysate (HPL) could improve the expansion of human articular chondrocytes for autologous chondrocyte implantation (ACI), a cartilage regeneration treatment for osteoarthritis. The researchers compared HPL-supplemented medium to conventional expansion conditions during cell passages 2-4, measuring cell proliferation, chondrogenic markers, and cellular senescence, while also examining the underlying BMP-TAK1-p38 signaling pathway. HPL significantly enhanced chondrocyte proliferation and maintained chondrogenic phenotype while reducing cellular senescence compared to conventional expansion methods, with these beneficial effects mediated through BMP-2 signaling. These findings suggest that HPL could improve the clinical efficacy of ACI procedures by producing higher-quality chondrocytes for cartilage repair, and support the therapeutic potential of platelet-rich plasma treatments in osteoarthritis management.

THREE DECADES OF ADVANCEMENTS IN OSTEOARTHRITIS RESEARCH: INSIGHTS FROM TRANSCRIPTOMIC, PROTEOMIC, AND METABOLOMIC STUDIES.

This review examined three decades of osteoarthritis (OA) research using advanced molecular analysis techniques (transcriptomics, proteomics, and metabolomics) to better understand disease mechanisms and patient variability. The authors conducted a comprehensive literature search focusing on how these "omic" technologies have identified individual molecules, molecular patterns, and cellular subtypes in tissues and fluids from OA patients, including single-cell level analysis.

The studies revealed numerous specific molecules and pathways contributing to OA pathogenesis, identifying distinct cell subtypes and their associated disease mechanisms within affected tissues. However, the review highlighted that current research still needs to better map the spatial organization of these cellular subtypes and molecular patterns within OA-affected joints.

The authors conclude that integrating multiple omic approaches with patients' clinical and demographic characteristics holds promise for identifying unique patient endophenotypes (distinct biological subgroups). This comprehensive approach could help clinicians understand the significant variability between OA patients and ultimately enable the development of personalized therapeutic interventions and targeted physiotherapy strategies tailored to specific patient subgroups rather than using one-size-fits-all treatments.

IRON OVERLOAD CAUSES MACROPHAGES TO PRODUCE A PRO-INFLAMMATORY PHENOTYPE IN THE SYNOVIUM OF HEMOPHILIAC ARTHRITIS VIA THE ACETYL-P53 PATHWAY.

This study investigated how iron overload drives inflammation in hemophiliac arthritis by examining the molecular mechanisms underlying macrophage behavior in joint tissue. Researchers compared synovial tissue from hemophiliac arthritis patients and healthy controls using histological analysis, iron staining, and protein detection methods, plus created laboratory models using iron-treated immune cells. The key finding was that excess iron in hemophiliac joints triggers a specific molecular pathway (acetyl-P53) that transforms macrophages into a pro-inflammatory M1 phenotype, leading to increased production of inflammatory substances and joint inflammation. These results suggest that targeting iron overload or the acetyl-P53 pathway could offer new therapeutic approaches for managing hemophiliac arthritis, potentially informing rehabilitation strategies that address the underlying inflammatory processes rather than just mechanical joint problems.

IMAGING MASS CYTOMETRY REVEALS TISSUE-SPECIFIC CELLULAR IMMUNE PHENOTYPES IN THE MOUSE KNEE FOLLOWING ACL INJURY.

This study developed an advanced imaging technique (imaging mass cytometry) to identify specific immune cell types and their interactions in mouse knee tissues following ACL injury. Researchers used a controlled compression injury model in mice, comparing different injury severities (sham, mild, and severe compression causing ACL rupture) and analyzed immune cell populations in the synovium and infrapatellar fat pad two weeks post-injury. The method identified 11 distinct immune cell subgroups in the synovium and 7 in the fat pad, with approximately half of these populations significantly increased after severe ACL injury, particularly around blood vessels. This research reveals that different knee tissues have unique immune responses to injury, suggesting that future osteoarthritis treatments and rehabilitation strategies may need to be tailored to target specific tissue compartments rather than using a one-size-fits-all approach.

NETWORK-BASED CYTOKINE INFERENCE IMPLICATES ONCOSTATIN M AS A DRIVER OF AN INFLAMMATION PHENOTYPE IN KNEE OSTEOARTHRITIS.

This study aimed to understand how aging affects inflammatory processes in knee osteoarthritis by using network-based analysis to identify key cytokines driving cartilage degradation. The researchers employed computational network analysis of injured young and aged mouse knees, combined with pharmacological manipulation and phenotypic drug discovery approaches to map cytokine-mediated communication between synovium and cartilage. The key finding was that aged knees showed aberrant matrix remodeling as a unique transcriptomic response, with oncostatin M (OSM), an IL-6 family member, identified as the primary driver of this "inflammatory" osteoarthritis phenotype characterized by accelerated cartilage degradation. These findings suggest that targeting OSM and related inflammatory pathways could provide new therapeutic opportunities for managing inflammation-driven osteoarthritis, particularly in older patients, potentially informing more personalized treatment approaches in musculoskeletal rehabilitation.

UNMET NEED IN RHEUMATOLOGY: REPORTS FROM THE ADVANCES IN TARGETED THERAPIES MEETING, 2023.

This study reports findings from the 2023 Advances in Targeted Therapies meeting, where over 100 international experts identified key unmet scientific needs across major rheumatological conditions including osteoarthritis (OA). The method involved disease-specific breakout sessions where experts prioritized current gaps in clinical and translational research for conditions including rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, vasculitis, and osteoarthritis. A major finding specific to OA was the critical need to develop reliable methods for phenotyping and stratifying patients for clinical trials, while across all conditions experts identified the need for better disease endotyping, biomarkers for predicting treatment response and disease progression, and innovative clinical trial designs. These findings highlight that for OA management and research, developing robust patient phenotyping approaches should be a priority to enable more personalized treatment strategies and improve clinical trial outcomes in physiotherapy and other interventions.

DISEASE PROGRESSION AND CLINICAL OUTCOMES IN LATENT OSTEOARTHRITIS PHENOTYPES: DATA FROM THE OSTEOARTHRITIS INITIATIVE.

This study aimed to identify distinct knee osteoarthritis phenotypes and develop tools to predict disease progression using machine learning analysis of the Osteoarthritis Initiative dataset. The researchers used unsupervised machine learning to identify patient subgroups, then developed supervised models using clinical variables to predict outcomes and total knee replacement risk.

The analysis revealed four distinct knee OA phenotypes characterized by different patterns of nutrition, disability, stiffness, and pain (both knee and back pain), with these phenotypes showing strong associations with disease progression outcomes. Surprisingly, the absence of supplemental vitamins in patients' diets was associated with protection from disease progression, contrary to common assumptions about nutritional supplementation.

The researchers developed a practical clinical tool using just five variables (WOMAC disability and total scores for both knees, plus vitamin/supplement usage) that can identify patient phenotype and predict progression risk in individual patients. This phenotyping approach could enable physiotherapists and clinicians to personalize treatment strategies, focus on modifiable risk factors, and better counsel patients about their long-term prognosis and need for interventions like total knee replacement.

SYNOVIAL-TISSUE RESIDENT MACROPHAGES PLAY PROINFLAMMATORY FUNCTIONS IN THE PATHOGENESIS OF RA WHILE MAINTAINING THE PHENOTYPES IN THE STEADY STATE.

This study investigated how synovial tissue-resident macrophages (STRMs) respond to rheumatoid arthritis (RA)-related inflammatory signals, compared to peripheral blood monocyte-derived macrophages (PBMOMs). The researchers isolated STRMs from osteoarthritis joint tissue and exposed both cell types to RA-related stimuli including immune complexes and inflammatory mediators like TNF-α. Key findings revealed that while PBMOMs showed dramatic phenotypic changes (switching from anti-inflammatory to pro-inflammatory markers), STRMs maintained their surface marker profile but still developed pro-inflammatory cytokine production and promoted inflammation in co-cultured synovial fibroblasts. These results suggest that resident joint macrophages contribute to RA pathogenesis through functional changes rather than complete phenotypic reprogramming, indicating that therapeutic strategies targeting joint inflammation may need to address both the distinct responses of tissue-resident and infiltrating immune cells.

SPECIFIC-CYTOKINE ASSOCIATIONS WITH OUTCOMES IN KNEE OSTEOARTHRITIS SUBGROUPS: BREAKING DOWN DISEASE HETEROGENEITY WITH PHENOTYPING.

This study aimed to validate and further characterize four previously identified knee osteoarthritis inflammatory phenotypes (KOIP) by examining how specific cytokines relate to disease severity and progression within each subgroup. The researchers analyzed 13 cytokines in plasma and synovial fluid from 168 symptomatic female knee OA patients with joint effusion, comparing cytokine-outcome associations within individual phenotype groups versus the overall patient population.

The key finding was that cytokine associations with OA outcomes were significantly stronger when analyzed within specific phenotype subgroups rather than across all patients, with several cytokines showing phenotype-specific behaviors. This suggests that knee OA consists of distinct inflammatory subtypes with different underlying biological pathways, which may explain why previous cytokine studies in OA have produced inconsistent results.

These findings support the clinical value of phenotyping OA patients, as it could enable better patient stratification, more targeted anti-inflammatory treatments, and improved prediction of disease progression—all of which could inform more personalized physiotherapy and rehabilitation approaches.

PAIN-PHENOTYPING IN OSTEOARTHRITIS: CURRENT CONCEPTS, EVIDENCE, AND CONSIDERATIONS TOWARDS A COMPREHENSIVE FRAMEWORK FOR ASSESSMENT AND TREATMENT.

This narrative review aimed to synthesize current knowledge on pain phenotypes in osteoarthritis (OA) and propose a framework for comprehensive pain assessment. The authors conducted a literature search focusing on pain-phenotyping in knee OA, examining various assessment approaches including patient-reported outcomes, comorbidity evaluations, psychological measures, and quantitative sensory testing.

The review identified relatively consistent pain phenotypes in knee OA, particularly a high-pain phenotype where pain levels don't necessarily correspond to structural joint damage, and a low-pain/low-impact phenotype. Additional subgroups can be distinguished using multiple assessment domains including psychological factors (anxiety, depression), sleep patterns, activity levels, and objective sensory testing measures.

The findings highlight that OA pain is complex and multidimensional, requiring systematic assessment across multiple domains rather than relying solely on structural changes or simple pain ratings. For clinical practice and physiotherapy, this suggests the need for comprehensive pain phenotyping to enable more personalized treatment approaches, moving beyond one-size-fits-all interventions toward targeted management strategies based on individual pain profiles and associated factors.

THE PHENOTYPIC DIVERSITY OF ANTEROMEDIAL OSTEOARTHRITIS BEFORE AND AFTER TREATMENT WITH MEDIAL UNICOMPARTMENTAL KNEE ARTHROPLASTY: A RADIOGRAPHIC ANALYSIS OF 1000 KNEES.

This study investigated the diversity of knee alignment patterns (phenotypes) in 1000 knees with anteromedial osteoarthritis before and after medial unicompartmental knee arthroplasty (UKA), using detailed radiographic measurements of hip-knee-ankle angles and bone positioning. The researchers identified 76 distinct alignment phenotypes before surgery (25 common ones) and 58 after surgery (17 common ones), demonstrating remarkable diversity in how osteoarthritis affects knee alignment in this predominantly Caucasian population. The key finding was that knees with combined deformities affecting both the femur and tibia were less likely to achieve restoration of their original pre-arthritic alignment after UKA surgery compared to knees with single-bone deformities or no extra-articular deformity. These results suggest that surgeons should consider individual phenotypic variations when planning UKA procedures, as certain alignment patterns may require modified surgical approaches or alternative treatments to optimize outcomes and restore natural knee mechanics.

FUNCTIONAL KNEE PHENOTYPES: A HELPFUL CLASSIFICATION TOOL FOR VISUALIZING POTENTIAL FEMORAL VARUS IN RESTRICTED KINEMATIC ALIGNMENT TOTAL KNEE ARTHROPLASTY IN JAPAN.

This study aimed to examine the distribution of functional knee phenotypes in Japanese patients undergoing total knee arthroplasty (TKA) and evaluate whether restricted kinematic alignment (RKA) achieves better anatomical outcomes than mechanical alignment (MA). The researchers analyzed 114 TKA surgeries, measuring joint alignment angles and categorizing knees using functional phenotype classification, with clinical outcomes assessed at 3 years post-surgery.

The most common preoperative phenotype was a varus hip-varus knee-varus ankle pattern (11.4% of cases), with nearly half (44.7%) showing significant femoral varus ≥3°, suggesting distinct racial morphological characteristics in the Japanese population. After surgery, RKA achieved neutral alignment more frequently than MA, with 72% vs 27% of cases having joint lines within 3° of parallel to the ground.

The functional knee phenotyping classification appears to be a valuable tool for identifying patients with femoral varus deformity who may benefit from RKA rather than traditional MA techniques, potentially improving surgical planning and outcomes in TKA, though both approaches showed similar clinical outcomes at 3 years.

MICROGEL-BASED CARRIERS ENHANCE SKELETAL STEM CELL REPROGRAMMING TOWARDS IMMUNOMODULATORY PHENOTYPE IN OSTEOARTHRITIC THERAPY.

This study investigated how microgel carriers could enhance the therapeutic potential of skeletal stem cells (SSCs) for osteoarthritis treatment by promoting their immunomodulatory properties. The researchers used single-cell RNA sequencing to analyze SSC subpopulations and tested microgel-delivered SSCs in osteoarthritic rats, examining their effects on inflammation and joint protection.

The key finding was that microgel carriers mechanically activated SSCs to develop a specific immunomodulatory phenotype (PDPN+ GREM1+ PTGS2+) that effectively suppressed inflammatory macrophages through a YAP-mediated pathway, leading to reduced pro-inflammatory markers (TNF-α, IL-1β) and increased anti-inflammatory signals (IL-10).

In the rat osteoarthritis model, microgel-delivered SSCs provided superior joint protection and reduced macrophage activation compared to SSCs alone, while also improving cell retention time in the joint. This research suggests that combining stem cell therapy with mechanical activation through delivery systems could enhance treatment outcomes in osteoarthritis by targeting the inflammatory component of the disease, potentially offering new therapeutic strategies beyond traditional tissue repair approaches.

MACROPHAGE MIGRATION INHIBITORY FACTOR REVERSED SENESCENT PHENOTYPE IN HUMAN CHONDROCYTES IN VITRO.

This study investigated how macrophage migration inhibitory factor (MIF) affects chondrocyte aging in osteoarthritis (OA), using laboratory experiments with human joint fluid samples and chondrocyte cultures. Researchers found that MIF levels were significantly elevated in OA patients' synovial fluid, and when applied to aged chondrocytes (induced by LPS treatment), MIF successfully reversed cellular aging markers while enhancing cartilage-producing genes (COL II, SOX9, ACAN) and reducing cell death. The findings suggest that higher MIF levels in arthritic joints may represent a protective response that helps maintain healthy cartilage-producing cells and prevents cellular aging. These results indicate that targeting the MIF pathway could offer new therapeutic approaches for OA treatment, potentially informing future rehabilitation strategies that combine biological interventions with traditional physiotherapy approaches.

MOLECULAR PORTRAIT OF CHRONIC JOINT DISEASES: DEFINING ENDOTYPES TOWARD PERSONALIZED MEDICINE.

This review aimed to examine how molecular endotypes (biologically-defined disease subtypes) could advance personalized medicine for three major joint diseases: rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA). The authors conducted a narrative review exploring the progression from clinical phenotyping to molecular endotyping across these conditions, examining epidemiological, clinical, and molecular characteristics. The study highlights that while clinical phenotypes have improved disease management, emerging molecular endotypes reveal greater biological diversity underlying these joint diseases than previously recognized. These findings suggest that future personalized treatment approaches, including physiotherapy interventions, should consider both clinical presentations and underlying molecular mechanisms to optimize patient outcomes and address the significant proportion of patients who currently lack effective disease management.

ASSOCIATION BETWEEN HIGH HBA1C LEVELS AND MAST CELL PHENOTYPE IN THE INFRAPATELLAR FAT PAD OF PATIENTS WITH KNEE OSTEOARTHRITIS.

This study investigated how diabetes affects mast cell activity in the infrapatellar fat pad (IPFP) of knee osteoarthritis patients to better understand the link between diabetes and knee OA. Researchers compared IPFP tissue samples from 156 knee OA patients, dividing them into high diabetes markers (HbA1c ≥6.5, n=28) and normal groups (HbA1c <6.5, n=128), then used propensity matching and isolated mast cell-rich versus mast cell-poor tissue fractions to analyze mast cell markers and gene expression.

The key finding was that patients with high HbA1c levels had significantly higher levels of mast cell markers in their IPFP tissue, indicating more mast cells were present, but individual mast cells showed similar characteristics regardless of diabetes status. This suggests that diabetes creates a distinct inflammatory phenotype in knee OA characterized by increased mast cell infiltration in the fat pad behind the kneecap, rather than changes in mast cell behavior itself.

These findings identify diabetic knee OA patients as a specific subgroup with heightened IPFP inflammation, which could guide targeted anti-inflammatory treatments and help physiotherapists understand why diabetic patients may experience different pain and inflammation patterns during rehabilitation.

CHALLENGES AND PROMISE OF TARGETING MIRNA IN RHEUMATIC DISEASES: A COMPUTATIONAL APPROACH TO IDENTIFY MIRNA ASSOCIATION WITH CELL TYPES, CYTOKINES, AND DISEASE MECHANISMS.

This computational study aimed to systematically identify and rank the most research-relevant microRNAs (miRNAs) across nine rheumatic diseases, including osteoarthritis, by analyzing their co-occurrence patterns in the existing literature. The researchers used PowerShell programming to scan PubMed publications and count unique co-occurrences of individual miRNAs with disease names, immune cells, cytokines, and pathological processes, creating ranked matrices to identify research "hotspots." The analysis revealed three key miRNAs (miR-146, miR-155, and miR-21) that are consistently relevant across multiple rheumatic diseases, while also identifying unique miRNAs specific to individual conditions like osteoarthritis. This computational approach provides researchers and clinicians with a systematic "relevance finder" tool to guide future miRNA-based therapeutic development and helps prioritize which epigenetic targets may be most promising for treating specific rheumatic disease phenotypes.

ANALYSIS OF GRAFT TYPES AUGMENTED WITH AN INTERNAL BRACE FOR ACL RECONSTRUCTION: A SYSTEMATIC REVIEW.

This systematic review aimed to compare the effectiveness of suture tape (ST) augmentation across different graft types used in ACL reconstruction surgery. The authors analyzed 10 studies from 926 initially identified papers, examining outcomes for hamstring tendon (50% of studies), quadriceps tendon (30%), and bone-patellar tendon-bone grafts (10%) when augmented with internal bracing.

The review found that all graft types showed biomechanical improvements with ST augmentation, including reduced graft elongation (15-56% for hamstring), increased load to failure, and improved stiffness compared to non-augmented grafts. Clinically, ST-augmented grafts demonstrated significantly less knee laxity and, in some cases, better patient-reported outcomes, with low complication rates across all graft types.

These findings suggest that internal bracing with suture tape may enhance ACL reconstruction outcomes regardless of graft choice, potentially reducing failure rates and revision surgery needs. For rehabilitation professionals, this technique may allow for more confident early mobilization protocols, though specific rehabilitation modifications for ST-augmented grafts require further investigation.

SPATIAL ANALYSIS OF THE OSTEOARTHRITIS MICROENVIRONMENT: TECHNIQUES, INSIGHTS, AND APPLICATIONS.

This review examines how advanced spatial analysis techniques can improve understanding of osteoarthritis (OA) tissue microenvironments to support better disease characterization and treatment development. The authors discuss cutting-edge molecular imaging methods including high-resolution microscopy, hyperspectral imaging, and mass spectrometry imaging that can analyze the spatial distribution of DNA, RNA, proteins, and metabolites within intact joint tissues. These techniques reveal that OA encompasses distinct molecular endotypes (inflammatory, metabolic, mechanical, genetic, and synovial variants) with specific spatial patterns that traditional bulk tissue analysis methods cannot detect. The spatial mapping approach offers significant potential for developing precision diagnostic tools and targeted therapies by enabling clinicians to identify specific OA phenotypes and their underlying molecular mechanisms, which could ultimately lead to more personalized physiotherapy and treatment strategies.

USING TWO PREDICTIVE MODELS TO CAPTURE TWO TYPES OF POOR OUTCOMES IN KNEE ARTHROPLASTY: A MULTISITE LONGITUDINAL COHORT STUDY.

**Study Summary:**

This multisite study of 565 knee arthroplasty patients aimed to comprehensively determine poor outcome risk and identify predictive factors using two complementary analytical approaches. The researchers applied latent class analysis (LCA) to identify poor outcome trajectories based on pain and disability scores, and used the modified Escobar appropriateness system to classify surgical candidates, then developed prediction models incorporating preoperative prognostic variables. The study identified two distinct types of poor outcomes—minimal improvement and poor final outcomes—with combined estimates showing 34-45% of patients at high risk for poor results, nearly double the commonly reported 20% rate, and consistently found greater contralateral knee pain as a key predictor of poor outcomes. These findings suggest that preoperative screening using both appropriateness criteria and trajectory-based predictors could help clinicians identify high-risk patients and optimize surgical timing or explore alternative management strategies, potentially reducing poor outcome rates through better patient selection.

METABOLOMIC PROFILES AND PATHWAYS IN OSTEOARTHRITIC HUMAN CARTILAGE: A COMPARATIVE ANALYSIS WITH HEALTHY CARTILAGE.

This study aimed to identify distinct metabolic profiles in osteoarthritic cartilage compared to healthy tissue and to classify metabolic subtypes within osteoarthritis patients. Researchers used liquid chromatography-mass spectrometry to analyze metabolites from cartilage samples collected from 35 osteoarthritis patients undergoing joint replacement surgery and 11 healthy controls from a tissue bank. The analysis revealed significant differences in amino acid and lipid pathways between healthy and osteoarthritic cartilage, affecting energy production, tissue maintenance, and cellular function, and identified four distinct metabolic subtypes (endotypes) within the osteoarthritis group. These findings highlight the metabolic diversity within osteoarthritis patients and suggest that different subtypes may require tailored treatment approaches, potentially informing personalized physiotherapy interventions and targeted therapeutic strategies based on individual metabolic profiles.

DISEASE PROGRESSION AND CLINICAL OUTCOMES IN LATENT OSTEOARTHRITIS PHENOTYPES: DATA FROM THE OSTEOARTHRITIS INITIATIVE.

This study aimed to identify distinct knee osteoarthritis phenotypes and develop tools to predict disease progression using data from the Osteoarthritis Initiative. Researchers applied unsupervised machine learning to discover phenotypes and supervised learning to create predictive models, analyzing patient factors including nutrition, disability, stiffness, and pain levels. Four distinct knee OA phenotypes were identified, characterized by different combinations of nutrition patterns, disability levels, stiffness, and pain (both knee and back), with the surprising finding that absence of vitamin supplementation was actually protective against disease progression. The researchers developed a practical clinical tool using just 5 variables (WOMAC disability and total scores for both knees, plus vitamin/supplement usage) that can help clinicians identify patient phenotypes, predict progression risk and need for knee replacement, enabling more personalized treatment approaches for osteoarthritis management.

FROM BIOCHEMICAL MARKERS TO MOLECULAR ENDOTYPES OF OSTEOARTHRITIS: A REVIEW ON VALIDATED BIOMARKERS.

This narrative review aimed to examine validated biochemical markers that could identify distinct molecular endotypes (mechanistic disease subgroups) in osteoarthritis, moving beyond observable symptoms to understand underlying disease drivers. The authors conducted a comprehensive literature search to analyze panels of tissue- and pathology-specific biochemical markers and their associations with key OA pathologies, drawing on validated approaches from major research initiatives like IMI-APPROACH and OAI-FNIH. The review found that panels of biochemical markers can successfully identify disease subgroups and help classify patients into treatable molecular endotypes that reflect specific pathobiological mechanisms rather than just clinical symptoms. These findings suggest that biochemical marker-based endotyping could revolutionize OA management by enabling precision medicine approaches, allowing clinicians and researchers to match patients to targeted therapies based on their specific disease mechanisms rather than using one-size-fits-all symptomatic treatments.

INFRAPATELLAR FAT PAD ADIPOSE TISSUE-DERIVED MACROPHAGES DISPLAY A PREDOMINANT CD11C+CD206+ PHENOTYPE AND EXPRESS GENOTYPES ATTRIBUTABLE TO KEY FEATURES OF OA PATHOGENESIS.

This study aimed to characterize macrophage subpopulations in knee osteoarthritis (OA) tissues and investigate how the local joint environment influences their behavior. Researchers used flow cytometry and gene expression analysis to examine macrophages from infrapatellar fat pads (IPFPs) and synovial tissues of knee OA patients, and tested how different joint-derived factors affected macrophage polarization in laboratory experiments.

The key finding was that CD11C+CD206+ macrophages were the predominant subtype in both IPFPs and synovial tissues, and these cells showed high expression of genes linked to OA disease processes. Importantly, the tissue microenvironment significantly influenced macrophage behavior - IPFP-derived factors promoted one type of macrophage activation while synovial tissue factors promoted another, and macrophage abundance did not correlate with cartilage damage severity.

The study demonstrates that platelet-rich plasma (PRP) treatment can partially reverse pathological macrophage profiles, suggesting potential therapeutic applications. For clinicians and physiotherapists, these findings highlight that OA involves complex immune responses that vary between joint tissues, and support the rationale for investigating PRP and other treatments that can modulate the inflammatory environment in OA management.

COVALENT CONJUGATION OF SMALL MOLECULE INHIBITORS AND GROWTH FACTORS TO A SILK FIBROIN-DERIVED BIOINK TO DEVELOP PHENOTYPICALLY STABLE 3D BIOPRINTED CARTILAGE.

This study aimed to develop a 3D bioprinted cartilage graft that remains stable and resistant to osteoarthritic changes for treating cartilage lesions. The researchers covalently attached three therapeutic molecules (LDN193189, TGFβ3, and IL-1 receptor antagonist) to a silk fibroin-gelatin bioink containing human bone marrow stromal cells, then exposed the printed constructs to osteoarthritis-inducing conditions for 14 days. Despite notable variation between individual donors, the IL-1 receptor antagonist showed the greatest promise, enhancing healthy cartilage gene expression while reducing inflammatory markers and preventing the formation of hypertrophic (overgrown) cartilage tissue. This approach offers a potential new treatment strategy for osteoarthritis by creating engineered cartilage grafts that can resist degenerative changes, though the substantial donor variability suggests patient-specific factors may influence treatment outcomes in clinical applications.

METABOLOMIC PROFILES OF CARTILAGE AND BONE REFLECT TISSUE TYPE, RADIOGRAPHY-CONFIRMED OSTEOARTHRITIS, AND SPATIAL LOCATION WITHIN THE JOINT.

This study aimed to identify metabolic differences in osteoarthritic joint tissues by analyzing cartilage and bone samples from different disease grades and joint locations. The researchers used liquid chromatography-mass spectrometry to analyze metabolites from cartilage and subchondral bone samples obtained from 9 human femoral heads during hip replacement surgery, comparing late-stage osteoarthritis (grades III and IV) across different joint regions.

The study identified distinct metabolic "endotypes" or subgroups based on tissue type (cartilage vs. bone), disease severity (grade III vs. IV), and spatial location within the joint, with lipid and amino acid metabolism pathways being key distinguishing factors between tissues. Importantly, the researchers found that metabolic changes were not uniform across the joint - certain pathways like glycosaminoglycan degradation and amino acid metabolism were concentrated in specific regions of the femoral head.

These findings suggest that osteoarthritis presents as distinct metabolic subgroups rather than a uniform disease process, which could inform more targeted therapeutic approaches and help explain why joint damage patterns vary between patients, potentially leading to more personalized physiotherapy and treatment strategies.

ONLY 26% OF NATIVE KNEES SHOW AN IDENTICAL CORONAL FUNCTIONAL KNEE PHENOTYPE IN THE CONTRALATERAL KNEE.

This study examined whether people's left and right knees have similar structural characteristics by analyzing 3D scans of 282 healthy knees from 141 patients aged 16-45 years. Using advanced SPECT/CT imaging, researchers measured 23 different knee shape and alignment parameters across three anatomical planes and classified knees into functional phenotypes (structural subtypes). The key finding was that only 26% of people had identical knee phenotypes between their left and right sides in the coronal (front-to-back) plane, though 67% had similar adjacent phenotypes, with stronger correlations found in the coronal and sagittal planes compared to the axial plane. These findings suggest that clinicians should avoid assuming both knees are structurally identical when planning treatments like knee replacements or corrective surgeries, and could help develop more personalized, individualized approaches to knee osteoarthritis management and rehabilitation strategies.

PHENOTYPES OF OSTEOARTHRITIS-RELATED KNEE PAIN AND THEIR TRANSITION OVER TIME: DATA FROM THE OSTEOARTHRITIS INITIATIVE.

This study aimed to identify distinct knee osteoarthritis pain phenotypes and track how they change over time, along with risk factors for developing worse pain patterns. Using data from 4,796 participants in the Osteoarthritis Initiative, researchers applied latent transition analysis to WOMAC pain scores to identify phenotypes and their 24-month transition patterns.

The analysis revealed four distinct pain phenotypes: no pain, mild pain during activity only, mild pain during both rest and activity, and moderate pain during both rest and activity. While most participants remained in their baseline phenotype over 24 months, notable transitions occurred—including substantial remission rates of 46-55% in the two worst phenotypes, but also progression in 17% of initially pain-free knees.

Key risk factors for worse pain phenotypes included being female, non-white ethnicity, higher depression scores, higher BMI, greater radiographic severity, and previous knee injury, while older age (≥65 years) and higher education were protective. These findings suggest that pain phenotyping could help physiotherapists and clinicians better predict pain trajectories and tailor interventions, particularly targeting modifiable risk factors like BMI and depression in high-risk patients.

NO CLINICAL OUTCOME DIFFERENCE BETWEEN VARUS PHENOTYPES AFTER MEDIAL OPENING-WEDGE HIGH TIBIAL OSTEOTOMY AT 2 YEARS FOLLOW-UP.

This retrospective study investigated whether different varus knee phenotypes, classified using the Coronal Plane Alignment of the Knee (CPAK) system, show varying clinical outcomes after medial opening-wedge high tibial osteotomy (MOWHTO). The researchers analyzed 135 patients over 2 years, categorizing them based on tibial and femoral alignment angles and measuring outcomes using pain scales, knee function scores, and therapeutic response rates.

The study found that while CPAK 1 (52%) was the most common preoperative phenotype and CPAK 6 (49%) the most common postoperative phenotype, all varus phenotypes showed significant clinical improvement with no meaningful differences between groups at 2-year follow-up. Therapeutic response rates ranged from 64-87% across phenotypes, with no statistically significant differences.

These findings suggest that MOWHTO can be effective across different varus phenotypes, including femoral-driven and constitutional varus knees, not just the traditional tibial varus cases. For clinicians, this supports expanding surgical indications beyond medial arthritic varus knees with isolated tibial deformity, potentially benefiting a broader range of patients with knee malalignment.

GENDER-BASED DIFFERENCES EXIST IN THE FUNCTIONAL KNEE PHENOTYPES CLASSIFICATION OF THE OSTEOARTHRITIC KNEE.

This study aimed to identify gender differences in functional knee phenotypes and joint alignment patterns in osteoarthritic knees using CT imaging data from 12,099 patients (5,025 male, 7,074 female). The researchers analyzed hip-knee-ankle angles, femoral and tibial mechanical angles, and joint line convergence angles using specialized software to classify patients into functional phenotypes.

The analysis revealed 127 distinct phenotypes in males and 131 in females, with 17 common phenotypes shared between genders, though the four most common phenotypes were similar across both groups (affecting 6-10% of patients each). Key differences emerged in that males showed significantly greater femoral varus deformity compared to females, while tibial alignment patterns remained similar between genders.

These findings suggest that gender-specific considerations should be incorporated into osteoarthritic knee assessment and treatment planning, particularly regarding femoral alignment variations, which could inform more personalized approaches to total knee arthroplasty and potentially guide targeted physiotherapy interventions for different phenotypic presentations.

TRANSCRIPTOMIC PROFILING OF OSTEOARTHRITIS SYNOVIAL MACROPHAGES REVEALS A TOLERIZED PHENOTYPE COMPOUNDED BY A WEAK CORTICOSTEROID RESPONSE.

This study investigated why corticosteroid treatments don't improve long-term osteoarthritis outcomes by examining the molecular response of immune cells (macrophages) in arthritic joints. Researchers used genome-wide gene expression analysis to compare how macrophages from end-stage osteoarthritis joints respond to corticosteroids versus laboratory models of inflammatory and anti-inflammatory macrophage states.

The key finding was that osteoarthritis joint macrophages showed a severely blunted response to corticosteroids, with only 12 genes changing expression compared to 201-257 genes in the comparison models. These osteoarthritis macrophages displayed a "tolerized" inflammatory profile similar to chronically suppressed immune cells, but with distinct features including high levels of tissue-damaging enzymes (metalloproteinases) and specific inflammatory signals.

This tolerized, corticosteroid-resistant phenotype provides a biological explanation for why steroid injections fail to provide lasting benefits in osteoarthritis patients. For clinicians and physiotherapists, these findings support focusing on non-pharmacological interventions like exercise and movement therapies rather than relying on repeated corticosteroid treatments for long-term osteoarthritis management.

FUNCTIONAL KNEE PHENOTYPES APPEAR TO BE MORE SUITABLE FOR THE CHINESE OA POPULATION COMPARED WITH CPAK CLASSIFICATION: A STUDY BASED ON 3D CT RECONSTRUCTION MODELS.

This study aimed to compare two knee classification systems (CPAK and functional knee phenotypes) in Chinese osteoarthritis patients to identify optimal alignment strategies for total knee arthroplasty (TKA). Using 3D CT reconstruction models from 434 Chinese OA patients, researchers measured various knee alignment angles and categorized patients according to both classification systems, then evaluated different surgical alignment approaches.

The study found that functional knee phenotypes showed much greater diversity (140 different phenotypes) compared to CPAK classification, with Chinese OA patients demonstrating a predominant varus (inward) knee alignment pattern primarily due to tibial bone changes rather than femoral changes. Over 70% of patients had different alignment patterns in their femur and tibia bones, suggesting complex individual variations.

The functional knee phenotype system appeared more suitable for the Chinese OA population due to its wider distribution patterns and better representation of the varus tendency common in this group. For surgical management, the findings suggest that adjusted mechanical alignment (AMA) and restricted kinematic alignment (RKA) approaches may be more appropriate TKA strategies for Chinese patients, as these methods better preserve individual bone anatomy compared to traditional mechanical alignment techniques.

PROGNOSTIC VALUE OF B-SCORE FOR PREDICTING JOINT REPLACEMENT IN THE CONTEXT OF OSTEOARTHRITIS PHENOTYPES: DATA FROM THE OSTEOARTHRITIS INITIATIVE.

This study aimed to evaluate whether combining clinical phenotype clusters with a machine-learning derived bone shape measure (B-score) could improve prediction of knee replacement surgery in osteoarthritis patients. Using longitudinal data from the Osteoarthritis Initiative, researchers analyzed previously established clinical phenotype clusters alongside 3D bone shape B-scores, employing Cox regression models and survival analyses to predict knee replacement over 9 years.

The study found that B-scores varied significantly across different clinical phenotype clusters, with higher scores in clusters characterized by more comorbidities and inflammatory signs, and that 9.4% of participants underwent knee replacement during follow-up. Both clinical phenotypes and B-scores independently predicted knee replacement risk, but combining them provided superior predictive accuracy, particularly benefiting patients with less pain and radiographic severity but limited physical activity.

These findings suggest that integrating bone shape analysis with clinical phenotyping could enhance patient stratification for clinical trials and improve risk prediction in practice, potentially allowing physiotherapists and clinicians to identify high-risk patients earlier and tailor management strategies accordingly.

TIBIA-FIRST, GAP-BALANCED PATIENT-SPECIFIC ALIGNMENT RESTORES BONY PHENOTYPES AND JOINT LINE OBLIQUITY IN A GREAT MAJORITY OF VARUS AND STRAIGHT KNEES AND NORMALISES VALGUS AND SEVERE VARUS DEFORMITIES.

This study evaluated whether a patient-specific alignment (PSA) technique in total knee replacement could restore individual knee anatomy patterns rather than using a standard alignment approach for all patients. Researchers analyzed 367 patients who underwent navigated knee replacement surgery using a tibia-first, gap-balanced PSA method, classifying knees by their natural alignment patterns (CPAK classification) before and after surgery.

The technique successfully restored the original bone structure and joint line orientation in over 70-75% of naturally straight knees and 40-50% of knock-kneed (varus) patients, while severely misaligned knees (extreme varus and valgus deformities) were normalized rather than restored to their original patterns. Phenotype restoration was achieved in 85% of straight legs, 94% of varus knees, but only 37% of valgus knees, with significant improvements in joint line positioning across all groups.

These findings suggest that personalized alignment techniques can preserve individual knee anatomy in most patients with mild to moderate deformities, potentially leading to more natural knee function and better patient outcomes compared to standard alignment approaches in knee replacement surgery.

REGULATION OF OXYGEN TENSION AS A STRATEGY TO CONTROL CHONDROCYTIC PHENOTYPE FOR CARTILAGE TISSUE ENGINEERING AND REGENERATION.

This narrative review examined whether controlling oxygen levels could improve chondrocyte (cartilage cell) characteristics for cartilage tissue engineering and regeneration approaches. The authors reviewed existing literature on how oxygen tension affects the metabolism and phenotype regulation of different cartilage cell types, including articular chondrocytes, growth plate chondrocytes, and progenitor cells, along with other microenvironmental factors that influence these cells. The key finding is that cartilage naturally exists in low-oxygen conditions, and chondrocytes are well-adapted to this environment, suggesting that manipulating oxygen levels could be used to control cell behavior and maintain optimal cartilage cell characteristics. For clinical management, this research suggests that controlling oxygen tension during cell-based cartilage repair procedures could potentially improve treatment outcomes by ensuring that regenerated tissue maintains proper cartilage cell properties, addressing a current limitation where repair tissue often lacks optimal chondrocyte characteristics.

FUNCTIONAL ANALYSIS OF CELL LINES DERIVED FROM SMAD3-RELATED LOEYS-DIETZ SYNDROME PATIENTS PROVIDES INSIGHTS INTO GENOTYPE-PHENOTYPE RELATION.

This study aimed to investigate how different types of SMAD3 gene variants affect disease severity in Loeys-Dietz syndrome type 3 (LDS3), a condition characterized by blood vessel problems and osteoarthritis. Researchers analyzed clinical data from patients and conducted laboratory tests on cell lines derived from these patients, specifically examining fibroblasts (connective tissue cells) and vascular smooth muscle cells.

The study identified two distinct phenotypic subgroups: patients with dominant negative (DN) variants experienced more severe cardiovascular events at younger ages (average 35 years) compared to those with haploinsufficient (HI) variants (average 46 years). At the cellular level, DN variants showed reduced cell differentiation ability and impaired formation of extracellular matrix, while HI variants demonstrated increased differentiation potential and altered muscle protein expression.

These findings suggest that genetic testing should distinguish between DN and HI SMAD3 variants to predict disease severity and guide personalized management strategies, with DN variant patients requiring earlier and more intensive cardiovascular monitoring and potentially different approaches to managing their osteoarthritis and connective tissue manifestations.

ASTAXANTHIN REDUCES INFLAMMATION AND PROMOTES A CHONDROGENIC PHENOTYPE BY UPREGULATING SIRT1 IN OSTEOARTHRITIS.

This study investigated whether astaxanthin (AST), a natural antioxidant compound, could protect against osteoarthritis by influencing SIRT1 protein signaling pathways. Researchers used mouse models with surgically-induced OA and laboratory cell cultures treated with inflammatory substances to test AST's effects through imaging, molecular, and tissue analysis methods. The key finding was that AST treatment promoted a protective cartilage cell phenotype by reducing inflammation, decreasing cartilage-degrading enzymes, and increasing cartilage matrix proteins, with these benefits dependent on upregulating SIRT1 protein expression. These results suggest AST could serve as a potential therapeutic agent for early-stage OA management, though clinical translation and optimal dosing strategies for musculoskeletal rehabilitation programs require further investigation.

PHENOTYPE-CONSIDERED KINEMATICALLY ALIGNED TOTAL KNEE ARTHROPLASTY FOR WINDSWEPT-DEFORMITY-ASSOCIATED OSTEOARTHRITIS: SURGICAL STRATEGY AND CLINICAL OUTCOMES.

This study investigated windswept deformity (WSD) - a condition where one knee bends inward and the other outward - in patients with advanced osteoarthritis requiring total knee replacement surgery. The researchers analyzed 40 knees from 33 WSD patients who underwent a specialized surgical approach called phenotype-considered kinematically aligned total knee arthroplasty (KA-TKA) between 2016-2020, comparing outcomes between the inward-bending (varus) and outward-bending (valgus) knees.

The study found that 64% of WSD patients had spinal imbalance and 21% had unequal leg lengths, suggesting these conditions are interconnected. Both varus and valgus knees showed significant improvements in alignment, range of motion, and functional scores after surgery, with no meaningful differences in functional outcomes between the two knee types despite different alignment measurements.

These findings suggest that WSD represents a distinct osteoarthritis phenotype often associated with spinal problems and leg length differences, requiring specialized surgical planning that considers the whole-body biomechanics rather than treating each knee in isolation.

THREE-DIMENSIONAL-BASED NATIVE ALIGNMENT PHENOTYPE CLASSIFICATION SYSTEM: DESCRIPTION FOR USE IN PLANNING FOR DEFORMITIES DURING TOTAL KNEE ARTHROPLASTY.

This study developed a new classification system for knee alignment patterns to improve surgical planning for total knee arthroplasty (TKA) by using detailed 3D CT scans instead of traditional 2D X-rays. Researchers analyzed pre-operative CT scans from 1,406 patients and used robotic surgery systems to measure knee deformities in both coronal (side-to-side) and sagittal (front-to-back) planes, categorizing deformities into 5-degree ranges.

The analysis identified 77 distinct alignment phenotypes, with the most common being mild varus deformity (inward angulation) of 6-10 degrees (36.9% of cases) and mild flexion contractures of 0-5 degrees (32.6% of cases). When combining both planes, the most frequent pattern was mild varus with mild flexion contracture (12.5% of cases).

This 3D-based phenotyping system could significantly improve TKA outcomes by enabling surgeons to better understand individual knee anatomy and plan more personalized surgical approaches, moving away from one-size-fits-all procedures toward precision medicine in knee replacement surgery.

FIBROCYTE PHENOTYPE OF ENTPD1+CD55+ CELLS AND ITS ASSOCIATION WITH PAIN IN OSTEOARTHRITIC SYNOVIUM.

This study investigated specific cell types in the joint lining (synovium) of osteoarthritis patients to better understand pain mechanisms and identify potential treatment targets. The researchers used advanced protein analysis techniques to compare two types of synovial fibroblasts - those expressing both ENTPD1 and CD55 markers versus those expressing only CD55 - focusing on their molecular characteristics and relationship to patient-reported pain levels. The key finding was that ENTPD1+CD55+ cells showed a distinct "fibrocyte" profile with increased expression of proteins involved in tissue scarring and extracellular matrix remodeling, and importantly, the presence of these cells was associated with resting pain in osteoarthritis patients. These results suggest that targeting ENTPD1-expressing fibrocytes could offer new therapeutic approaches for managing osteoarthritis pain, potentially informing future rehabilitation strategies that address both the inflammatory and fibrotic components of joint pathology.

GENOTYPE AND PHENOTYPE IN PATIENTS WITH ACAN GENE VARIANTS: THREE CASES AND LITERATURE REVIEW.

This study aimed to characterize the clinical features and treatment responses in patients with ACAN gene variants that cause familial short stature. The researchers analyzed three new families with novel ACAN variants and conducted a comprehensive literature review of 314 individuals from 105 families, examining the genetic variants and associated physical characteristics.

The analysis identified distinct phenotypic features including short stature, early-onset osteoarthritis, brachydactyly (short fingers), midfacial underdevelopment, and premature growth cessation, though no clear relationship between specific genetic variants and clinical severity was found. Notably, the early-onset osteoarthritis represents a key musculoskeletal manifestation that would require long-term monitoring and management.

Treatment with recombinant human growth hormone (rhGH) showed significant benefits, with treated children achieving better final heights compared to untreated individuals. For physiotherapists and clinicians, these findings highlight the importance of recognizing this genetic condition early, as patients will likely require specialized care for both growth issues and joint problems, with genetic testing being essential for accurate diagnosis.

DEFICIENCY OF CBFΒ IN ARTICULAR CARTILAGE LEADS TO OSTEOARTHRITIS-LIKE PHENOTYPE THROUGH HIPPO/YAP, TGFΒ, AND WNT/Β-CATENIN SIGNALING PATHWAYS.

This study investigated the role of core binding factor subunit β (CBFβ) in osteoarthritis development by examining mice with CBFβ deficiency specifically in their joint cartilage. Researchers used genetically modified mice, advanced imaging techniques, gene expression analysis, and protein studies to understand how CBFβ deficiency affects cartilage health. The key finding was that mice lacking CBFβ in their joint cartilage spontaneously developed osteoarthritis-like changes, including cartilage breakdown and inflammation, through disruption of three critical cellular signaling pathways (Hippo/YAP, TGFβ, and Wnt/β-catenin) that normally maintain healthy cartilage. These results suggest that CBFβ could represent a new therapeutic target for osteoarthritis treatment, potentially informing future development of treatments that could complement existing physiotherapy and rehabilitation approaches by targeting the underlying molecular mechanisms of cartilage degeneration.

CLINICAL PHENOTYPES OF COMORBIDITIES IN END-STAGE KNEE OSTEOARTHRITIS: A CLUSTER ANALYSIS.

This study aimed to identify distinct clinical phenotypes based on comorbidity patterns in patients with end-stage knee osteoarthritis to improve individualized care approaches. The researchers used cluster analysis on 23 variables (demographics, comorbidities, inflammatory markers, and clinical assessments) from 421 patients undergoing knee surgery, applying factor analysis followed by two-step clustering methods.

Four distinct phenotypes emerged: an "obesity + hypertension" group (93.8% obese, 71.2% hypertensive), a "depression + anxiety" group (95.8% depressed, 94.7% anxious), an "isolated end-stage knee osteoarthritis" group with minimal comorbidities, and a "rheumatoid arthritis" group (58.8% with RA). These phenotypes suggest that patients with end-stage knee osteoarthritis present with distinct comorbidity clusters that could guide targeted treatment strategies, such as addressing metabolic factors in the obesity phenotype, psychological support for the mental health phenotype, or anti-inflammatory approaches for the RA phenotype.

TOLL-LIKE RECEPTOR ACTIVATION REGULATES THE PARACRINE EFFECT OF ADIPOSE-DERIVED MESENCHYMAL STEM CELLS ON REVERSING OSTEOARTHRITIC PHENOTYPE OF CHONDROCYTES.

This laboratory study investigated how different inflammatory signals affect the ability of adipose-derived mesenchymal stem cells (ADSCs) to reverse cartilage damage in osteoarthritis. The researchers pre-treated rat ADSCs with two different inflammatory molecules (TLR3 or TLR4 activators) and then examined their effects on damaged cartilage cells using co-culture systems and molecular analysis techniques.

The key finding was that ADSCs responded differently depending on which inflammatory signal they received - TLR3 activation caused ADSCs to produce IL-10 and effectively reverse osteoarthritic changes in cartilage cells (promoting cell survival, reducing cartilage-degrading enzymes, and increasing cartilage matrix proteins), while TLR4 activation led to IL-6 production without these beneficial effects. This suggests that the inflammatory environment within osteoarthritic joints creates distinct ADSC phenotypes with varying therapeutic potential.

These findings help explain why stem cell injections for osteoarthritis show inconsistent clinical results, as the specific inflammatory conditions in each patient's joint may determine treatment effectiveness. This research suggests that future stem cell therapies might need to be tailored based on the inflammatory profile of individual patients, or that pre-conditioning stem cells with specific signals could improve treatment outcomes.

WNT5A DEFICIENCY IN OSTEOCALCIN-EXPRESSING CELLS COULD NOT ALLEVIATE THE OSTEOARTHRITIC PHENOTYPE IN A MOUSE MODEL OF POST-TRAUMATIC OSTEOARTHRITIS.

This study investigated whether deleting WNT5A protein in bone-forming cells could prevent osteoarthritis development, since WNT5A is known to be overexpressed in OA tissues. Researchers used genetically modified mice (WNT5A-CKO) and induced knee OA through surgical ligament transection, then assessed cartilage damage and bone changes after 8 weeks using histological analysis and micro-CT imaging. Both knockout and control mice developed similar severe OA features, including cartilage degeneration, increased cell death, reduced protective proteins, and deteriorated bone structure beneath the cartilage, with no significant differences between groups. These findings suggest that targeting WNT5A in bone cells alone may not be an effective therapeutic strategy for post-traumatic osteoarthritis, indicating that clinicians and researchers should explore alternative molecular targets or combination approaches for OA prevention and treatment.

ASSESSING THE CAUSAL ASSOCIATIONS OF DIFFERENT TYPES OF STATINS USE AND KNEE/HIP OSTEOARTHRITIS: A MENDELIAN RANDOMIZATION STUDY.

This study used Mendelian randomization to investigate whether different types of statin medications causally reduce the risk of developing knee and hip osteoarthritis. The researchers analyzed genetic data from large genome-wide association studies, using genetic variants as natural experiments to assess causal relationships between statin use and osteoarthritis risk, while controlling for cholesterol levels and body mass index.

The analysis revealed that statin use was associated with a 5% reduced risk of knee osteoarthritis and 7% reduced risk of hip osteoarthritis, with atorvastatin and simvastatin showing protective effects for both joints, while rosuvastatin only protected against hip osteoarthritis. The protective effects appeared to work through lowering LDL and IDL cholesterol levels rather than through other mechanisms, and body mass index played an important mediating role.

These findings suggest that statins may help prevent osteoarthritis development, particularly in patients already prescribed these medications for cardiovascular conditions. For clinicians and physiotherapists, this research supports considering statin therapy as part of a comprehensive osteoarthritis prevention strategy, especially in patients with elevated cholesterol who are at risk for joint disease.

METABOLOMIC PROFILES AND PATHWAYS IN OSTEOARTHRITIC HUMAN CARTILAGE: A COMPARATIVE ANALYSIS WITH HEALTHY CARTILAGE.

This study aimed to identify metabolic differences between healthy and osteoarthritic cartilage and explore metabolic heterogeneity within osteoarthritis using liquid chromatography-mass spectrometry to analyze cartilage samples from 11 healthy individuals and 35 end-stage OA patients. The analysis revealed distinct alterations in lipid and amino acid metabolic pathways in OA cartilage, indicating disrupted energy production, cartilage matrix maintenance, and mitochondrial function compared to healthy tissue. Importantly, the osteoarthritic cartilage samples clustered into four distinct metabolic subgroups (endotypes), demonstrating significant metabolic heterogeneity within OA patients. These findings suggest that OA management and physiotherapy approaches may need to be tailored based on underlying metabolic phenotypes, and the identified metabolic markers could potentially guide personalized treatment strategies or serve as targets for novel therapeutic interventions.

PREOPERATIVE PHENOTYPE HAS NO SIGNIFICANT IMPACT ON THE CLINICAL OUTCOMES AND LONG-TERM SURVIVAL OF MECHANICALLY ALIGNED TOTAL KNEE ARTHROPLASTY IN ASIAN PATIENTS WITH OSTEOARTHRITIS.

This study investigated whether different knee alignment patterns (phenotypes) in Asian patients with end-stage osteoarthritis affected outcomes after mechanically aligned total knee arthroplasty (TKA). Researchers analyzed 945 TKAs from 641 patients, classifying them into 12 phenotypes based on overall leg alignment and joint line angles, then compared clinical scores and implant survival rates over 15 years. The most common phenotypes were mild-to-moderate varus alignment patterns, and overall there were no significant differences in clinical outcomes or long-term survival between different phenotypes. However, for one specific phenotype group, patients whose alignment was corrected to neutral during surgery had better 15-year implant survival (95%) compared to those whose natural alignment was preserved (74%), suggesting that mechanical alignment correction may be beneficial for certain phenotypes despite the general finding that constitutional alignment variations don't significantly impact TKA outcomes.

HAND OSTEOARTHRITIS PHENOTYPES BASED ON A BIOPSYCHOSOCIAL APPROACH, AND THEIR ASSOCIATIONS WITH CROSS-SECTIONAL AND LONGITUDINAL PAIN.

This study aimed to identify distinct hand osteoarthritis (OA) phenotypes using a biopsychosocial approach and examine their relationships with pain outcomes over time. Researchers used latent class analysis on baseline data from the NOR-HAND study to identify patient subgroups based on radiographic severity, ultrasound findings, demographics, psychosocial factors, and pain sensitization, then tracked pain outcomes over 3.5 years using linear regression models.

Five distinct phenotypes were identified that differed in structural OA severity and biopsychosocial burden. Notably, patients with the least severe structural OA but higher biopsychosocial burden (including psychological distress and pain sensitization) reported the highest hand pain levels, while those with the most severe structural damage but low biopsychosocial burden had less pain - demonstrating a clear symptom-structure mismatch.

These findings highlight that pain severity in hand OA is driven more by biopsychosocial factors than structural damage alone, suggesting that physiotherapy and management approaches should prioritize comprehensive biopsychosocial assessment and interventions (such as pain education, psychological support, and central sensitization management) rather than focusing solely on structural severity when treating hand OA patients.

NA

This study aimed to investigate whether senescent immune cells in the blood could serve as biomarkers for osteoarthritis and age-related orthopedic decline. Researchers used a fluorescent compound (C12FDG) to detect senescent peripheral blood mononuclear cells (PBMCs) and T cells in a large cohort of healthy individuals and osteoarthritis patients, while also measuring related serum biomarkers.

The key finding was that patients with mild to moderate osteoarthritis had significantly elevated levels of senescent immune cells compared to healthy controls, with levels increasing alongside age and inflammatory markers. Importantly, participants taking the senolytic drug fisetin showed reduced senescent cell percentages, suggesting these cells may be modifiable therapeutic targets.

These results suggest that measuring senescent immune cells could potentially be used to identify osteoarthritis phenotypes characterized by higher systemic inflammation and cellular aging. For clinical management, this approach may help identify patients who could benefit from anti-senescence therapies alongside traditional physiotherapy interventions, potentially offering a more personalized treatment approach for osteoarthritis based on underlying cellular aging processes.

CLINICAL PHENOTYPES, MOLECULAR ENDOTYPES AND THERATYPES IN OA THERAPEUTIC DEVELOPMENT.

I apologize, but I cannot provide a summary of this research paper because the abstract is listed as "NA" (not available).

To write an accurate and meaningful summary focusing on the study objective, methods, phenotype findings, and physiotherapy implications, I would need access to the actual abstract content that describes:

- The study's aims and design
- The methodological approach used
- The specific phenotypes or subgroups identified
- The clinical or therapeutic implications discussed

If you could provide the complete abstract, I would be happy to create a concise 3-4 sentence summary suitable for clinicians and researchers working in osteoarthritis phenotyping and musculoskeletal rehabilitation.

TWO-YEAR POST-DISTRACTION CARTILAGE-RELATED STRUCTURAL IMPROVEMENT IS ACCOMPANIED BY INCREASED SERUM FULL-LENGTH SIRT1.

This study investigated whether different forms of the protein SIRT1 in blood could predict treatment responses in knee osteoarthritis patients undergoing joint distraction therapy. Researchers measured two SIRT1 biomarkers - fragmented SIRT1 (NT/CT ratio) and full-length SIRT1 (FLSIRT1) - in serum samples from patients followed over two years after knee joint distraction treatment.

The findings revealed two distinct biomarker patterns: fragmented SIRT1 (higher NT/CT ratio) at baseline was associated with more severe osteoarthritis features like osteophytes and bone/cartilage breakdown markers, while increased full-length SIRT1 levels after treatment correlated with structural improvements, particularly reduced bone damage and better cartilage outcomes.

These results suggest that measuring different SIRT1 forms could help identify patient subgroups - those with high baseline fragmented SIRT1 may have more severe disease, while patients who develop higher full-length SIRT1 levels appear more likely to experience structural benefits from joint distraction therapy, potentially guiding treatment selection and monitoring in clinical practice.

PRESERVATION OF PREARTHRITIC CORONAL KNEE PHENOTYPE AND PREARTHRITIC CORONAL ALIGNMENT YIELDED IMPROVED KUJALA SCORES FOLLOWING LIGAMENT-GUIDED MEDIAL UNICOMPARTMENTAL KNEE ARTHROPLASTY.

This study examined how different knee alignment patterns (phenotypes) affect outcomes following robotic-assisted, ligament-guided medial unicompartmental knee arthroplasty (UKA) in 618 patients over an average 4-year follow-up. The researchers analyzed coronal plane alignment of the knee (CPAK) phenotypes and sagittal tibial wear patterns, comparing patient-reported outcomes and implant survival rates between different phenotypic groups. The key finding was that patients whose natural knee alignment pattern was preserved during surgery, rather than altered, achieved significantly better Kujala scores (a knee function measure), though other outcome measures and implant survival rates were similar across all phenotypes. These results suggest that surgeons should aim to maintain each patient's individual pre-arthritic knee alignment during UKA surgery, supporting a personalized surgical approach rather than targeting a standardized alignment for all patients.

CAUSAL RELATIONSHIP BETWEEN PERIODONTAL DISEASE-RELATED PHENOTYPE AND KNEE OSTEOARTHRITIS: A TWO-SAMPLE MENDELIAN RANDOMIZATION ANALYSIS.

This study investigated the bidirectional causal relationship between periodontal disease-related phenotype (PDRP) and knee osteoarthritis (KOA) using Mendelian randomization analysis of genetic data from nearly 404,000 individuals. The researchers employed multiple analytical methods (including inverse variance weighting and Egger regression) with genetic variants as instrumental variables to establish causality while controlling for confounding factors like smoking, alcohol consumption, and BMI.

The analysis initially found evidence for a causal relationship from periodontal disease to knee osteoarthritis, but not in the reverse direction, suggesting that gum disease may contribute to knee joint degeneration. However, when accounting for important lifestyle and demographic confounders, this causal relationship was no longer supported, with smoking and higher BMI emerging as the primary independent risk factors for knee osteoarthritis.

These findings suggest that the apparent link between periodontal disease and knee osteoarthritis may be largely explained by shared risk factors rather than direct causation, emphasizing the importance of addressing smoking cessation and weight management in both dental and musculoskeletal health interventions.

KNEES WITH ISOLATED LATERAL COMPARTMENT OSTEOARTHRITIS SHOW A SUBSTANTIAL VARIABILITY IN FUNCTIONAL KNEE PHENOTYPES WITH DEMOGRAPHIC-SPECIFIC VARIATIONS: PHENOTYPIC ANALYSIS OF 305 KNEES.

This study aimed to characterize the diverse functional knee phenotypes in isolated lateral compartment osteoarthritis and examine demographic variations. Researchers analyzed 305 knees using a comprehensive classification system based on mechanical hip-knee-ankle angle, femoral mechanical angle, and tibial mechanical angle measurements in the coronal plane.

The analysis revealed remarkable phenotypic diversity, identifying 60 distinct functional knee phenotypes among patients with isolated lateral compartment OA, with significant demographic variations: females showed greater valgus alignment than males, while younger patients predominantly had femoral deformities compared to older patients who typically exhibited tibial or combined deformities.

These findings highlight the need for individualized assessment and treatment approaches in lateral compartment OA, as the substantial phenotypic variability suggests that standardized rehabilitation protocols may be inadequate for addressing the unique biomechanical characteristics and deformity patterns present in different patient subgroups.

RADIOLOGIC ASSESSMENT OF KNEE PHENOTYPES BASED ON THE CORONAL PLANE ALIGNMENT OF THE KNEE CLASSIFICATION IN A KOREAN POPULATION.

This study aimed to evaluate and modify the Coronal Plane Alignment of the Knee (CPAK) classification system for Korean populations, comparing knee alignment phenotypes between healthy and osteoarthritic knees. The researchers analyzed radiographic data from 1,000 knees (500 healthy, 500 osteoarthritic) using long-leg standing X-rays, measuring six alignment parameters and creating a modified CPAK system with adjusted boundaries to account for the more varus alignment typically seen in Asian populations.

The study identified nine distinct knee phenotypes with different distributions between healthy and osteoarthritic knees - Type II was most common in healthy knees (35-38%) while Type I predominated in osteoarthritic knees (38-54%), depending on the classification system used. The modified CPAK classification provided more even distribution across phenotypes compared to the original system, which showed clustering in certain categories when applied to the Korean population.

These findings suggest that knee alignment phenotyping may help identify individuals at risk for osteoarthritis development and could inform personalized treatment approaches, as different phenotypes may respond differently to specific interventions such as bracing, exercise therapy, or surgical planning in physiotherapy and orthopedic management.

COBALT IONS INDUCE A CELLULAR SENESCENCE SECRETORY PHENOTYPE IN HUMAN SYNOVIAL FIBROBLAST-LIKE CELLS THAT MAY BE AN EARLY EVENT IN THE DEVELOPMENT OF ADVERSE LOCAL TISSUE REACTIONS TO HIP IMPLANTS.

This study investigated how cobalt and chromium ions from metal hip implants affect synovial fibroblasts to better understand the development of adverse local tissue reactions (ALTRs) that occur in ~10% of patients with metal-on-metal hip replacements. The researchers exposed human synovial fibroblast-like cells to metal ions and used various laboratory techniques to assess cell viability, senescence markers, inflammatory factors, and oxidative stress pathways.

The key finding was that prolonged cobalt exposure caused synovial fibroblasts to enter a state of cellular senescence, characterized by reduced antioxidant enzyme activity, hydrogen peroxide accumulation, and increased production of pro-inflammatory substances including IL-1β, TNFα, and nerve growth factor (NGF). This research suggests that metal ion-induced cellular senescence in synovial tissue may be an early mechanism leading to ALTRs in hip implant patients, potentially informing strategies for early detection and management of implant-related complications through monitoring of inflammatory markers and synovial health.

AUTOLOGOUS PERIPHERAL BLOOD-DERIVED ORTHOBIOLOGICS: DIFFERENT TYPES AND THEIR EFFECTIVENESS IN MANAGING KNEE OSTEOARTHRITIS.

This editorial aimed to review the current evidence on autologous peripheral blood-derived orthobiologics (APBOs) - treatments using a patient's own blood components - for managing knee osteoarthritis. The authors conducted an overview of recent clinical studies examining various APBO formulations, including treatments like platelet-rich plasma and other blood-derived preparations. While many individual studies showed promising results for pain reduction and functional improvement with APBOs, the review identified a critical gap: there are no head-to-head comparison studies between different APBO types, making it difficult to determine which preparation works best for knee osteoarthritis patients. The authors conclude that larger, longer-term randomized controlled trials with direct comparisons are urgently needed to help clinicians choose the most effective APBO treatment and establish these therapies' role alongside conventional physiotherapy and management approaches.

LARGE VARIANCE IN A LATERAL OSTEOARTHRITIC POPULATION PRIOR TO AND FOLLOWING LATERAL UNICOMPARTMENTAL ARTHROPLASTY: AN ANALYSIS OF KNEE PHENOTYPES.

This study aimed to examine the variation in knee alignment patterns (phenotypes) before and after lateral unicompartmental knee arthroplasty (UKA) and determine whether specific alignment patterns were associated with better patient outcomes. The researchers analyzed radiographic measurements and patient-reported outcomes from 305 patients who underwent lateral UKA between 2012-2022, categorizing knees into different coronal plane alignment phenotypes and tracking outcomes using KOOS, Kujala, and satisfaction scores at one and two years.

The study found substantial variation in knee alignment patterns, with seven different phenotypes observed before surgery and all nine possible phenotypes present after surgery, indicating that lateral knee osteoarthritis affects patients with diverse knee geometries rather than a single alignment pattern. Notably, nearly one-quarter (23.6%) of patients with lateral compartment osteoarthritis did not have the expected valgus (knock-knee) alignment before developing arthritis.

No significant differences in patient-reported outcomes were found between different phenotypes or between patients whose natural alignment was preserved versus altered during surgery, suggesting there may not be a single optimal alignment target for all patients. These findings have important implications for surgical planning and rehabilitation, suggesting that individualized approaches based on patient-specific anatomy rather than universal alignment targets may be more appropriate for lateral UKA procedures.

RESTORING THE PREOPERATIVE PHENOTYPE ACCORDING TO THE CORONAL PLANE ALIGNMENT OF THE KNEE CLASSIFICATION AFTER TOTAL KNEE ARTHROPLASTY LEADS TO BETTER FUNCTIONAL RESULTS.

This retrospective multicenter study examined whether restoring patients' natural knee alignment patterns (phenotypes) during total knee arthroplasty (TKA) leads to better outcomes compared to the conventional approach of achieving neutral mechanical alignment. The researchers analyzed 178 TKA patients using the Coronal Plane Alignment of the Knee (CPAK) classification, which categorizes knees into 9 phenotypes based on limb alignment and joint line obliquity, comparing pre- and post-operative alignment patterns and functional outcomes at 2+ years follow-up.

The study found that conventional TKA techniques achieved true neutral mechanical alignment in only 37% of patients, with exact restoration of the patient's original CPAK phenotype occurring in just 15% of cases. Patients whose natural knee phenotype was successfully restored showed significantly better functional outcomes, particularly in daily living activities and quality of life measures compared to those whose constitutional alignment was altered.

These findings suggest that personalized alignment strategies that preserve each patient's individual knee phenotype may be superior to the traditional "one-size-fits-all" neutral alignment approach. For rehabilitation professionals, this highlights the importance of recognizing that patients may have different optimal alignment patterns, which could influence post-operative expectations, recovery trajectories, and the need for individualized physiotherapy approaches based on restored versus altered knee mechanics.

FIBROTIC PATHWAYS AND FIBROBLAST-LIKE SYNOVIOCYTE PHENOTYPES IN OSTEOARTHRITIS.

This review examined the role of fibrotic pathways and fibroblast-like synoviocytes (FLS) in osteoarthritis development and progression. The authors analyzed existing literature on FLS phenotypes, their spatial distribution in synovial tissue, and the mechanisms driving fibroblast-to-myofibroblast transformation in OA joints. The study identified two distinct FLS populations: a destructive THY1+ phenotype located in the synovial lining layer, and an invasive THY1- phenotype in the sublining layer that drives immune responses and synovitis. These findings suggest that targeting specific FLS phenotypes could lead to more personalized OA treatments, though the exact mechanisms controlling fibroblast activation remain unclear and require further research to develop effective therapeutic interventions for managing synovial inflammation and fibrosis.

EFFECT OF JOINT-LINE OBLIQUITY ON LONG-TERM SURVIVORSHIP OF TOTAL KNEE ARTHROPLASTY: A POSTOPERATIVE PHENOTYPE ANALYSIS.

This retrospective study investigated how different postoperative alignment patterns (phenotypes) affect the long-term survival of total knee arthroplasty (TKA) implants in 945 patients with primary osteoarthritis. The researchers classified patients into nine phenotypes based on their hip-knee-ankle alignment (neutral vs. varus) combined with joint-line obliquity measurements from standing X-rays, then tracked implant survival rates over 15 years using Kaplan-Meier analysis.

The study identified that patients with combined varus alignment and lateral joint-line inclination had significantly worse implant survival rates compared to the reference group (neutral alignment with parallel joint line), with 10- and 15-year survival dropping to 90% and 69% respectively versus 97% and 93% in the reference group. This specific phenotype also showed the highest failure rate at 18.3% compared to just 3.6% in the reference group.

These findings suggest that postoperative alignment phenotyping could help identify high-risk TKA patients who may benefit from closer monitoring and potentially different rehabilitation approaches, though the study focuses on implant survival rather than specific physiotherapy implications.

NEURAL EPIDERMAL GROWTH FACTOR-LIKE 1 PROTEIN (NELL-1) ALLEVIATES PERIODONTAL TISSUE DESTRUCTION IN PERIODONTITIS BY REGULATING THE RATIO OF M2/M1 MACROPHAGE PHENOTYPES.

This study investigated whether NELL-1 protein could reduce tissue damage in periodontitis by changing how immune cells (macrophages) behave. Researchers used a rat model of gum disease and treated macrophage cells in the lab, measuring tissue destruction, inflammation markers, and macrophage types using imaging, blood tests, and cellular analysis techniques. The key finding was that NELL-1 treatment shifted macrophages from a harmful "M1" type that promotes inflammation to a protective "M2" type that helps healing, leading to less bone and tissue damage in the gums. While this study focused on gum disease rather than joint conditions, the results suggest NELL-1 could potentially be developed as an anti-inflammatory treatment for musculoskeletal conditions like osteoarthritis, where similar macrophage imbalances contribute to tissue breakdown.

PROSPECTS OF DISEASE-MODIFYING OSTEOARTHRITIS DRUGS.

This review examines the prospects for disease-modifying osteoarthritis drugs (DMOADs) currently in phase 2/3 clinical trials, addressing the critical unmet need for treatments that can alter disease progression in a condition affecting nearly 23% of the global population. The author categorizes potential DMOADs based on three key osteoarthritis endotypes (distinct disease subtypes): inflammation-driven, bone-driven, and cartilage-driven pathways. The review identifies that different osteoarthritis phenotypes may respond to targeted therapies based on their underlying pathogenic mechanisms, suggesting a move toward personalized treatment approaches. For clinical practice and physiotherapy, this research highlights the importance of phenotyping patients to match them with appropriate interventions, potentially revolutionizing osteoarthritis management from symptom control to actual disease modification.

IMPORTANCE OF UNDERSTANDING PAIN PHENOTYPES IN KNEE OSTEOARTHRITIS FOR SELECTING APPROPRIATE PAIN-MANAGEMENT STRATEGIES.

I notice that the abstract is marked as "NA" (not available), so I can only provide a summary based on the title alone, which significantly limits the detail I can offer.

Based on the title, this study appears to focus on identifying different pain phenotypes (pain patterns or subtypes) in people with knee osteoarthritis to guide treatment selection. Without the abstract, I cannot describe the specific methods used, such as whether this was a systematic review, clinical study, or analysis of patient subgroups. The title suggests the main finding is that recognizing distinct pain phenotypes in knee osteoarthritis is crucial for effective treatment planning. The clinical implication appears to be that physiotherapists and clinicians should tailor pain management approaches based on individual pain characteristics rather than using a one-size-fits-all approach for knee osteoarthritis patients.

To provide a more comprehensive and accurate summary with the specific details you requested, I would need access to the complete abstract containing the study methodology, results, and conclusions.

EFFICACY AND SAFETY OF CULTURE-EXPANDED MESENCHYMAL STROMAL CELL THERAPY IN THE TREATMENT OF 4 TYPES OF INFLAMMATORY ARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF 36 RANDOMIZED CONTROLLED TRIALS.

This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of mesenchymal stem cell (MSC) therapy across four types of inflammatory arthritis. The researchers analyzed 36 randomized controlled trials involving 2,076 participants with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and systemic sclerosis, using comprehensive database searches and statistical meta-analysis.

The study found significant pain reduction benefits for osteoarthritis patients across all MSC sources (bone marrow, umbilical cord, and adipose tissue), with adipose tissue-derived MSCs showing the strongest improvements in pain, physical function, and overall WOMAC scores. For the other inflammatory arthritis conditions (rheumatoid arthritis, ankylosing spondylitis, and systemic sclerosis), MSC therapy showed potential therapeutic effects, though the evidence was less definitive.

These findings suggest that MSC therapy, particularly from adipose tissue sources, could serve as a viable treatment option for osteoarthritis management, potentially complementing traditional physiotherapy approaches by addressing both pain and functional limitations while maintaining a favorable safety profile.

MECHANICALLY ALIGNED TOTAL KNEE ARTHROPLASTY DOES NOT YIELD UNIFORM OUTCOMES ACROSS ALL CORONAL PLANE ALIGNMENT OF THE KNEE (CPAK) PHENOTYPES.

This retrospective study aimed to compare clinical outcomes across different coronal plane alignment of the knee (CPAK) phenotypes following mechanically aligned total knee arthroplasty (TKA). The researchers analyzed 180 patients who underwent mechanically aligned TKA with 1-year follow-up, classifying knee alignment using the CPAK system and measuring outcomes with validated scores including the Knee Society Score, Oxford Knee Score, and Forgotten Joint Score. Patients with preoperative varus alignment achieved significantly worse clinical outcomes compared to other alignment categories, with the varus group representing 39% of cases and apex distal phenotypes (Types I, II, III) being most common. These findings suggest that the standard mechanically aligned TKA approach may not be optimal for all patients, particularly those with varus alignment, indicating that personalized alignment strategies based on individual CPAK phenotypes could improve surgical outcomes and patient satisfaction.

THE ASSOCIATION BETWEEN IGF-1 LEVELS AND FOUR TYPES OF OSTEOARTHRITIS: A BIDIRECTIONAL AND TWO-STEP MENDELIAN RANDOMIZATION STUDY.

This study investigated the causal relationship between insulin-like growth factor-1 (IGF-1) levels and osteoarthritis across different joint sites, using bidirectional Mendelian randomization analysis of genome-wide association study data. The researchers employed multiple analytical methods to examine causality between IGF-1 and four types of OA (knee, hip, hand, and spine), while also investigating whether body mass index (BMI) mediates this relationship.

The findings revealed that higher IGF-1 levels causally increase the risk of knee, hip, and hand osteoarthritis, but not spine OA directly, with BMI serving as a mediating factor that explains how IGF-1 influences OA risk across all joint sites including the spine. Importantly, the study found no evidence that having OA affects IGF-1 levels, indicating a unidirectional relationship.

These results suggest distinct OA phenotypes based on joint location and their relationship to IGF-1, with implications for personalized management approaches that consider both metabolic factors (IGF-1) and weight management, particularly for physiotherapy interventions targeting weight control as a modifiable mediator of OA risk.

RADIOLOGICAL ASSESSMENT OF CORONAL PLANE ALIGNMENT OF THE KNEE PHENOTYPES IN THE ROMANIAN POPULATION.

This study aimed to determine the prevalence of knee alignment phenotypes in the Romanian population using the CPAK (Coronal Plane Alignment of the Knee) classification system, comparing osteoarthritic and healthy knees. The researchers conducted a cross-sectional analysis of 1,000 knees (500 osteoarthritic, 500 healthy), measuring radiological parameters including hip-knee angle and joint line obliquity to categorize knees into nine distinct phenotypes. The results showed that osteoarthritic knees were predominantly Type I phenotype (42.4%) characterized by varus alignment, while healthy knees were mainly Type II phenotype (39.0%) with neutral alignment, and certain phenotypes (Types VII-IX) were rare in both groups. These findings suggest that knee alignment phenotyping could be valuable for personalized treatment approaches in osteoarthritis management and may help physiotherapists tailor interventions based on specific biomechanical characteristics of different alignment patterns.

IL-40 IS UP-REGULATED IN THE SYNOVIAL FLUID AND CARTILAGE OF OSTEOARTHRITIS PATIENTS AND CONTRIBUTES TO THE ALTERATION OF CHONDROCYTES PHENOTYPE IN VITRO.

This study investigated the role of IL-40, a newly identified inflammatory cytokine, in osteoarthritis (OA) joint pathology and its effects on cartilage cells. Researchers analyzed cartilage samples and synovial fluid from OA patients compared to controls, using immunohistochemistry, ELISA, and in vitro cell culture experiments to examine IL-40 expression and its biological effects on chondrocytes.

The findings revealed significantly elevated IL-40 levels in OA synovial fluid compared to controls, with higher concentrations correlating with increased joint inflammation (synovial fluid white blood cell counts). IL-40 was present in cartilage cells, particularly in weight-bearing areas, and when applied to cartilage cells in laboratory conditions, it triggered a harmful inflammatory response by increasing production of inflammatory molecules (IL-6, IL-8) and cartilage-degrading enzymes (MMP-1, MMP-3, MMP-13).

These results suggest that IL-40 may drive cartilage cells toward a more destructive phenotype, contributing to the inflammatory and degenerative processes characteristic of OA. For clinical management, this identifies IL-40 as a potential biomarker for OA severity and inflammatory activity, and suggests that targeting IL-40 pathways could represent a novel therapeutic approach, though current physiotherapy interventions focusing on load

FEATURES ASSOCIATED WITH DIFFERENT INFLAMMATORY PHENOTYPES OF CALCIUM PYROPHOSPHATE DEPOSITION DISEASE: A STUDY USING DATA FROM THE INTERNATIONAL AMERICAN COLLEGE OF RHEUMATOLOGY/EULAR CALCIUM PYROPHOSPHATE DEPOSITION CLASSIFICATION CRITERIA COHORT.

This study aimed to identify the clinical and imaging characteristics that distinguish three inflammatory subtypes of calcium pyrophosphate deposition (CPPD) disease: recurrent acute attacks, chronic inflammatory arthritis, and crowned dens syndrome. Researchers analyzed data from 618 patients across 25 international sites using multivariable logistic regression to examine associations between patient features and each inflammatory phenotype.

The study identified distinct patterns for each subtype: recurrent acute CPPD was linked to longer disease duration, chronic inflammatory CPPD was associated with wrist involvement and hand osteoarthritis but less likely in patients with metabolic/familial risk factors, while crowned dens syndrome was more common in males and patients with extensive joint involvement. These findings demonstrate that CPPD disease presents as distinct inflammatory phenotypes rather than a single condition, each with specific clinical signatures.

For clinicians, recognizing these phenotypic differences could improve diagnostic accuracy and enable more targeted management approaches, particularly when assessing joint involvement patterns and considering underlying risk factors during patient evaluation.

RIFAMPIN-RESISTANT PERIPROSTHETIC JOINT INFECTIONS ARE ASSOCIATED WITH WORSE FUNCTIONAL OUTCOME IN BOTH ACUTE AND CHRONIC INFECTION TYPES.

This study investigated how rifampin resistance in periprosthetic joint infections (PJI) affects patient functional outcomes after treatment. The researchers compared 35 patients with rifampin-susceptible infections to 28 patients with rifampin-resistant infections over a 37-month follow-up period, using WOMAC scores to assess functional outcomes alongside tracking surgical revisions and treatment duration. Patients with rifampin-resistant infections had significantly worse functional outcomes (WOMAC scores: 71.5 vs 21.6 points), required nearly twice as many surgical revisions (6.9 vs 3.6), and needed longer antibiotic treatment courses, regardless of whether the infection was acute or chronic. These findings suggest that rifampin resistance creates a distinct phenotype of PJI patients who may require more intensive rehabilitation and modified treatment expectations, as they face prolonged recovery with substantially greater functional limitations even when infection control is achieved.

AUCUBIN SUPPRESSES TLR4/NF-ΚB SIGNALLING TO SHIFT MACROPHAGES TOWARD M2 PHENOTYPE IN GLUCOCORTICOID-ASSOCIATED OSTEONECROSIS OF THE FEMORAL HEAD.

This study investigated whether aucubin, a natural compound, could treat glucocorticoid-associated osteonecrosis of the femoral head (GONFH) by modulating immune cell responses. The researchers analyzed bone tissue from GONFH patients, tested aucubin treatment in a rat model of GONFH, and examined its effects on macrophage cells in culture, focusing on inflammatory (M1) versus healing-promoting (M2) macrophage types.

The key finding was that GONFH patients had significantly more pro-inflammatory M1 macrophages compared to anti-inflammatory M2 macrophages, along with elevated inflammatory signaling pathways, compared to patients with hip osteoarthritis. Aucubin treatment in rats dose-dependently reduced bone death and structural damage while shifting the immune response from harmful M1 macrophages toward beneficial M2 macrophages that promote healing.

These findings suggest that targeting macrophage polarization could be a promising therapeutic approach for GONFH, though this research focuses on pharmaceutical intervention rather than direct physiotherapy applications, and further clinical studies would be needed to translate these laboratory findings into patient care.

EXPLORING THE CAUSAL ASSOCIATION BETWEEN FRAILTY INDEX WITH THE COMMON TYPES OF ARTHRITIS: A MENDELIAN RANDOMIZATION ANALYSIS.

This study investigated whether genetic predisposition to frailty causally increases the risk of developing different types of arthritis using Mendelian randomization analysis of large biobank datasets (UK Biobank and FinnGen). The researchers used genetic variants associated with frailty index as instrumental variables to examine causal relationships with rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PSA), and ankylosing spondylitis (AS), employing inverse-variance weighted analysis as the primary method.

The findings revealed that genetic predisposition to higher frailty index was causally associated with increased risk of OA (odds ratios 1.03-1.55), RA (odds ratios 1.03-4.57), and PSA (odds ratio 4.22 in FinnGen), but not with ankylosing spondylitis. This suggests that frailty and certain arthritis types may share common biological pathways, with frailty potentially representing a distinct phenotype or predisposing factor rather than simply being a consequence of joint disease.

These results have important implications for clinical management, suggesting that frailty screening could help identify patients at higher risk for developing OA, RA, and PSA, potentially enabling earlier intervention and more personalized physiotherapy approaches that address both musculoskeletal and systemic

INCIDENCE OF OSTEOARTHRITIS BETWEEN ACL RECONSTRUCTION WITH DIFFERENT GRAFT TYPES AND BETWEEN ACL RECONSTRUCTION AND REPAIR: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS.

This systematic review and meta-analysis aimed to compare post-traumatic osteoarthritis (PTOA) development between different ACL reconstruction graft types and between ACL reconstruction versus repair. The researchers analyzed 11 randomized controlled trials including 1,015 patients with various graft types (hamstring tendon, bone-patellar tendon-bone, allograft, and ACL suture repair) with follow-up periods ranging from 2-12 years. The meta-analysis found no statistically significant differences in PTOA incidence between graft types, though bone-patellar tendon-bone grafts showed the highest raw percentage of PTOA (29.6%) compared to hamstring (23.4%), allograft (8.1%), and repair (0%). These findings suggest that graft choice may not be the primary driver of PTOA development, indicating that rehabilitation strategies should focus on optimizing knee function and biomechanics regardless of surgical technique, while highlighting the need for longer-term studies to better understand PTOA phenotypes after ACL injury.

PREDICTIVE AND CONCURRENT VALIDITY OF PAIN SENSITIVITY PHENOTYPE, NEUROPEPTIDOMICS AND NEUROEPIGENETICS IN THE MI-RAT OSTEOARTHRITIC SURGICAL MODEL IN RATS.

This study aimed to characterize pain-related biological markers and functional pain phenotypes in a rat model of osteoarthritis (OA) to better understand the mechanisms underlying OA pain processing. Researchers used the MI-RAT surgical model to induce OA in rats and assessed pain behaviors, joint structure, spinal neuropeptides, and micro-RNA expression over 56 days, comparing OA rats to healthy controls.

The study identified a complex pain phenotype in OA rats that included not only increased pain sensitivity (peripheral and central sensitization) but also enhanced pain inhibitory control mechanisms, alongside elevated pro-pain neuropeptides (substance P and bradykinin) and increased spinal micro-RNA-181b expression. Importantly, the findings revealed that OA pain involves active endogenous pain modulation systems rather than simply increased pain sensitivity.

These results suggest that effective OA management and physiotherapy should target both pain sensitization and the body's natural pain control mechanisms, potentially informing more personalized treatment approaches based on individual pain processing profiles rather than a one-size-fits-all strategy.

UNRAVELING THE JOINTS: A NARRATIVE REVIEW OF OSTEOARTHRITIS.

This narrative review aimed to comprehensively examine osteoarthritis (OA) as a complex joint disease, focusing on its underlying mechanisms, clinical presentation, and treatment approaches. The authors conducted a literature review to synthesize current knowledge about OA pathophysiology, phenotyping, and management strategies.

The review identifies three main molecular endotypes that drive OA: bone-driven, synovitis-driven, and cartilage-driven mechanisms, each involving different inflammatory pathways including interleukins and TNF-α. The authors emphasize that OA progresses through distinct stages (pre-OA, early OA, evident OA, and end-stage) with significant clinical variability between patients in terms of pain, stiffness, and functional limitations.

The findings highlight that OA heterogeneity necessitates personalized treatment approaches, with interventions ranging from risk factor modification and pharmacotherapy to rehabilitation, complementary therapies, and surgery depending on disease stage and endotype. For physiotherapy practice, this suggests that understanding a patient's specific OA endotype and disease stage could help tailor rehabilitation strategies, moving away from one-size-fits-all approaches toward more targeted interventions based on whether the primary drivers are bone, synovial, or cartilage-related pathology.

ULTRASMALL PRUSSIAN BLUE NANOZYME ATTENUATES OSTEOARTHRITIS BY SCAVENGING REACTIVE OXYGEN SPECIES AND REGULATING MACROPHAGE PHENOTYPE.

This study investigated whether ultrasmall Prussian blue nanoparticles (USPBNPs) could treat osteoarthritis by targeting reactive oxygen species (ROS) and inflammatory processes. The researchers developed sub-5 nm nanoparticles with antioxidant properties and tested their ability to eliminate ROS, modulate immune cell behavior, and treat OA in animal models.

The key finding was that USPBNPs effectively shifted macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype by reducing ROS levels and improving oxygen availability in joint tissues. In vivo testing showed that USPBNPs achieved therapeutic outcomes comparable to hydrocortisone treatment.

These results suggest a novel nanotechnology-based approach for OA management that targets the underlying inflammatory mechanisms rather than just symptoms, potentially offering clinicians a new treatment option that addresses the oxidative stress and immune dysregulation central to OA progression.

UNVEILING MRI-BASED STRUCTURAL PHENOTYPES IN TEMPOROMANDIBULAR JOINT OSTEOARTHRITIS: IMPLICATIONS FOR CLINICAL PRACTICE AND RESEARCH.

This study aimed to develop MRI-based structural phenotypes for temporomandibular joint (TMJ) osteoarthritis to address the clinical and imaging heterogeneity that makes disease management challenging. The researchers introduced the ROAMES-TMJ (Rapid Osteoarthritis MRI Eligibility Score for TMJ), which uses MRI as the reference standard to identify structural changes that align with histopathological findings in TMJ osteoarthritis. The approach recognizes that different TMJ osteoarthritis phenotypes exist with distinct clinical features, laboratory parameters, and imaging characteristics that can be detected through MRI assessment. This MRI-based phenotyping system has potential implications for improving patient selection in clinical trials, personalizing treatment approaches, and enhancing prognosis prediction, which could ultimately lead to more targeted physiotherapy and rehabilitation strategies for TMJ osteoarthritis management.

TARGETING FASCIN1 MAINTAINS CHONDROCYTES PHENOTYPE AND ATTENUATES OSTEOARTHRITIS DEVELOPMENT.

This study aimed to investigate the role of fascin actin-bundling protein 1 (FSCN1) in chondrocyte phenotype changes and osteoarthritis (OA) development. The researchers used proteome-wide screening, knockout mouse models, experimental OA surgery, and tested FSCN1 inhibitors in both animal models and human cartilage samples. They identified that FSCN1 is significantly upregulated in OA cartilage and accumulates in dedifferentiated chondrocytes, where it promotes harmful changes by activating TGF-β1/ALK1/SMAD signaling pathways that accelerate cartilage breakdown. The findings suggest that targeting FSCN1 with specific inhibitors could represent a promising new therapeutic approach for OA treatment, potentially offering a more targeted way to prevent chondrocyte dedifferentiation and maintain cartilage health compared to current management strategies.

COMPARATIVE STUDY ON THE ASSOCIATION BETWEEN TYPES OF PHYSICAL ACTIVITY, PHYSICAL ACTIVITY LEVELS, AND THE INCIDENCE OF OSTEOARTHRITIS IN ADULTS: THE NHANES 2007-2020.

This cross-sectional study analyzed NHANES data from 2007-2020 to determine which types and levels of physical activity are most effective at preventing osteoarthritis (OA) in adults. The researchers examined five categories of physical activity (vigorous and moderate work/recreational activities, plus walking/bicycling) using self-reported questionnaire data and weighted logistic regression analysis to assess associations with OA incidence.

The study found that recreational activities (both vigorous and moderate intensity) had protective effects against OA, while work-related activities showed mixed results depending on intensity levels. Importantly, the protective effects varied by age group (stronger in 20-64 year-olds) and gender, with males showing greater protection from both low and moderate activity levels compared to females.

These findings suggest that clinicians should prioritize recommending recreational physical activities over occupational activities for OA prevention, with moderate intensity levels appearing optimal for most adults, though individualized approaches considering age and gender may be warranted in rehabilitation planning.

MACROPHAGE AND CHONDROCYTE PHENOTYPES IN INFLAMMATION.

This focused review aimed to examine the phenotypic diversity of macrophages and chondrocytes in inflammatory conditions, particularly osteoarthritis, and explore how these phenotypes might be therapeutically modulated. The authors surveyed existing literature on macrophage polarization (M1 pro-inflammatory vs M2 anti-inflammatory/healing phenotypes, plus M17) and analogous phenotypic changes in chondrocytes, analyzing how various factors including cytokines, medications, and natural products influence these cellular states. The review highlights that both macrophages and chondrocytes can adopt different polarized phenotypes similar to T helper cell patterns, with chondrocytes showing particular phenotypic plasticity in osteoarthritis contexts. These findings suggest potential therapeutic opportunities for modulating cellular phenotypes to improve treatment outcomes, which could inform future physiotherapy approaches and rehabilitation strategies by targeting the inflammatory environment and promoting healing-oriented cellular responses in musculoskeletal conditions.

MULTI-OMICS INTEGRATIVE ANALYSES IDENTIFIED TWO ENDOTYPES OF HIP OSTEOARTHRITIS.

This study aimed to identify distinct molecular subtypes (endotypes) of hip osteoarthritis using multi-omics data integration. Researchers analyzed metabolomic profiles from blood, genome-wide genetic data, and cartilage gene expression in 180 hip OA patients and 120 controls, using machine learning methods to classify patients into subgroups. The analysis identified two distinct hip OA endotypes that could be distinguished with 96% accuracy using specific metabolite combinations (γ-aminobutyric acid, spermine, aconitic acid, and succinic acid), with the main differences between endotypes involving pro-inflammatory cytokine levels and energy metabolism pathways. These findings suggest that hip OA patients may benefit from personalized treatment approaches targeting either inflammatory processes or metabolic dysfunction, potentially informing more precise physiotherapy interventions and management strategies based on individual molecular profiles.

PHENOTYPIC VARIATIONS IN KNEE OSTEOARTHRITIS: INSIGHTS FROM MRI AND RADIOGRAPHIC COMPARISONS.

This study aimed to compare MRI-based knee osteoarthritis phenotypes (cartilage-meniscus, subchondral bone, and inflammatory) with traditional radiographic classifications (atrophic and hypertrophic) to demonstrate MRI's superior diagnostic capabilities. The researchers retrospectively analyzed knee radiographs and MRIs from 214 knees in 187 patients, using Kellgren-Lawrence staging and phenotype classification, with statistical analysis examining associations between imaging findings, disease severity, age, and gender. Key findings revealed that hypertrophic MRI phenotypes strongly correlated with cartilage-meniscus and subchondral bone damage, with these phenotypes being less common in early-stage disease (KL grade 2), more frequent subchondral bone involvement in men, and increased cartilage-meniscus phenotype in older patients. These results suggest that MRI provides more detailed phenotypic characterization than radiography alone, enabling clinicians and physiotherapists to develop more targeted, individualized treatment approaches based on the specific structural changes present in each patient's knee osteoarthritis.

GENDER, BMI, AND AGE-RELATED VARIATIONS IN LOWER LIMB ALIGNMENT PARAMETERS AND CPAK PHENOTYPES IN CHINESE PATIENTS WITH KNEE OSTEOARTHRITIS.

This study aimed to establish coronal plane alignment of the knee (CPAK) classification patterns in Chinese patients with knee osteoarthritis and examine how gender, BMI, and age influence lower limb alignment parameters. The researchers conducted a retrospective analysis of 944 osteoarthritic knees from 479 patients, measuring hip-knee-ankle angles and joint line obliquity, then categorizing patients into CPAK phenotypes using scatterplot distribution analysis. Key findings revealed that males and overweight/obese patients showed higher rates of constitutional varus alignment, while females and normal-weight patients more commonly had valgus alignment, though the predominant CPAK types (I, II, and IV) remained consistent across all demographic groups. These results suggest that while individual alignment parameters vary by gender and BMI, the underlying CPAK classification reliably reflects constitutional alignment patterns, which could inform personalized orthopedic and physiotherapy treatment strategies for knee osteoarthritis management.

PHENOTYPIC CLASSIFICATION AND FUNCTIONAL ASSESSMENT IN KNEE OSTEOARTHRITIS PATIENTS.

This prospective study aimed to classify knee osteoarthritis (KOA) patients into distinct phenotypes and assess their functional outcomes using standardized measures. Researchers studied 100 KOA patients over 17 months, categorizing them into five phenotypes based on clinical examination and tests: chronic pain (F1), inflammatory-predominant local pathology (F2), metabolic-predominant local pathology (F3), metabolic disorders (F4), and comorbidities including chronic venous insufficiency (F5). The key finding was that patients with metabolic disorders (F4) and comorbidities (F5) showed significantly greater improvements across all functional measures compared to other phenotypes, including reduced pain and better mobility, walking, dressing, and hand function. These results suggest that phenotype-based classification could help physiotherapists and clinicians tailor treatment approaches, with patients having metabolic conditions or comorbidities potentially responding better to rehabilitation interventions than those with primarily pain-driven or local inflammatory presentations.

SENOLYTIC THERAPY COMBINING DASATINIB AND QUERCETIN RESTORES THE CHONDROGENIC PHENOTYPE OF HUMAN OSTEOARTHRITIC CHONDROCYTES BY THE RELEASE OF PRO-ANABOLIC MEDIATORS.

This study investigated whether senolytic therapy using dasatinib and quercetin (D+Q) could restore healthy cartilage cell function in osteoarthritis by targeting aged, damaged cells. The researchers tested this drug combination on isolated human cartilage cells and cartilage tissue samples from early-stage OA patients, measuring cell senescence markers, cartilage-building genes, and inflammatory factors.

The D+Q treatment successfully eliminated senescent cells and significantly improved the cartilage-building (chondrogenic) phenotype, increasing production of key cartilage proteins like collagen type II while reducing harmful inflammatory signals. The therapy worked by creating a more favorable cellular environment through reducing damaging factors and increasing beneficial growth factors, with dasatinib being the primary active component.

These findings suggest that senolytic therapy could potentially modify OA disease progression by restoring cartilage cells' ability to maintain and repair tissue, representing a promising avenue for developing disease-modifying OA treatments that could complement current physiotherapy and rehabilitation approaches.

[HYALURONIC ACID IN THE TREATMENT OF OSTEOARTHRITIS: INNOVATIONS IN INJECTION THERAPY. A REVIEW].

This review examined the role of hyaluronic acid injection therapy in treating different osteoarthritis (OA) phenotypes and endotypes. The authors analyzed the mechanisms of action of various molecular weight sodium hyaluronate formulations and reviewed both international and Russian clinical studies on their efficacy and safety. The review highlights that OA heterogeneity based on pathophysiological features leads to distinct phenotypes and endotypes that may respond differently to treatment. The findings suggest that personalized hyaluronic acid therapy, exemplified by the Flexotron product line, can be tailored to specific OA phenotypes, potentially improving treatment outcomes by matching injection therapy characteristics to individual patient pathophysiology rather than using a one-size-fits-all approach.

JIANPI QINGRE TONGLUO PRESCRIPTION ALLEVIATES THE SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE WITH OSTEOARTHRITIS BY REGULATING STAG1/TP53/P21 SIGNALING PATHWAY.

This study investigated how Jianpi Qingre Tongluo Prescription (HQC), a traditional Chinese medicine compound, affects osteoarthritis by targeting cellular aging processes in cartilage. Researchers used both rat models of osteoarthritis and laboratory cell cultures, combining network pharmacology analysis with experimental validation to identify key molecular targets and pathways.

The study identified that HQC works by suppressing the senescence-associated secretory phenotype (SASP) - a harmful inflammatory state that aging cartilage cells develop - through regulation of the STAG1/TP53/P21 signaling pathway. Treatment with HQC reduced joint damage scores, decreased inflammatory markers (IL-1β, IL-6, MMP13), improved cartilage matrix proteins (collagen, aggrecan), and slowed cartilage cell death and aging.

These findings suggest that targeting cellular senescence pathways may represent a novel therapeutic approach for osteoarthritis management, potentially offering clinicians and physiotherapists insights into combination treatments that address both inflammation and cartilage preservation at the cellular level.

AN INNOVATIVE PHASE 2 CHRONIC PAIN MASTER PROTOCOL DESIGN TO ASSESS NOVEL MECHANISMS IN MULTIPLE PAIN TYPES.

This study describes an innovative master protocol design aimed at accelerating the testing of new pain medications across multiple chronic pain conditions simultaneously. The protocol uses statistical simulations and regulatory collaboration to efficiently evaluate novel drug mechanisms in three pain types: nociceptive pain (osteoarthritis), neuropathic pain (diabetic peripheral neuropathy), and mixed pain (chronic low back pain). Key advantages include reduced placebo exposure, smaller total sample sizes by sharing placebo data across studies, and the ability to directly compare different medications within each pain type. This approach could significantly speed up the development of targeted pain treatments and help identify which mechanisms work best for specific pain phenotypes, potentially leading to more personalized pain management strategies in clinical practice.

TAMARIXETIN PROTECTS CHONDROCYTES AGAINST IL-1Β-INDUCED OSTEOARTHRITIS PHENOTYPE BY INHIBITING NF-ΚB AND ACTIVATING NRF2 SIGNALING.

This study investigated whether tamarixetin, a natural flavonoid compound, could protect cartilage cells from osteoarthritis-related damage. Researchers used laboratory cell cultures, treating chondrocytes (cartilage cells) with IL-1β to simulate inflammatory conditions seen in osteoarthritis, then examining how tamarixetin affected cell behavior and molecular pathways. The key finding was that tamarixetin successfully prevented osteoarthritis-like changes in the cells by reducing inflammation through the NF-κB pathway while simultaneously boosting antioxidant defenses via the NRF2 pathway, effectively restoring normal cartilage cell function and preventing harmful cell death. These results suggest that compounds targeting both inflammatory and oxidative stress pathways simultaneously may represent a promising therapeutic approach for osteoarthritis management, potentially informing future development of treatments that could complement existing physiotherapy and rehabilitation strategies.

IDENTIFICATION OF A DUAL FUNCTIONAL BETULINIC ACID ANALOG FOR THE TREATMENT OF OSTEOARTHRITIS BY PHENOTYPIC SCREENING.

I apologize, but I cannot provide a meaningful summary of this study because the abstract is listed as "NA" (not available).

To write an accurate summary focusing on the study objective, methods, phenotype-related findings, and clinical implications for osteoarthritis management and physiotherapy, I would need access to the actual abstract content.

If you could provide the complete abstract text, I would be happy to create a concise 3-4 sentence summary in plain language suitable for clinicians and researchers working in osteoarthritis phenotyping and musculoskeletal rehabilitation.

ASSOCIATION OF MRI-BASED KNEE OSTEOARTHRITIS STRUCTURAL PHENOTYPES WITH SHORT-TERM STRUCTURAL PROGRESSION AND SUBSEQUENT TOTAL KNEE REPLACEMENT.

This study aimed to identify which MRI-based structural phenotypes of knee osteoarthritis are associated with disease progression and the need for total knee replacement. Researchers analyzed 733 participants from the Osteoarthritis Initiative, categorizing knees into three phenotypes based on MRI features: subchondral bone, meniscus/cartilage, and inflammatory phenotypes, then tracked structural changes over 24 months and knee replacement rates over 9 years.

The subchondral bone and inflammatory phenotypes were strongly linked to faster progression of joint damage (joint space narrowing, bone spurs, and sclerosis) and increased risk of requiring knee replacement, while the meniscus/cartilage phenotype showed weaker associations. Importantly, patients with overlapping phenotypes experienced even greater progression and replacement risk.

These findings suggest that MRI-based phenotyping could help clinicians identify high-risk patients who may benefit from more intensive monitoring and early intervention, while also providing a more targeted approach for selecting participants in future drug trials and rehabilitation studies.

MATRIKINE STIMULATION OF EQUINE SYNOVIAL FIBROBLASTS AND CHONDROCYTES RESULTS IN AN IN VITRO OSTEOARTHRITIS PHENOTYPE.

This study aimed to develop and validate an improved laboratory model of osteoarthritis using equine joint cells stimulated with fibronectin fragments (matrikines) naturally found in arthritic joints. Researchers isolated synovial fibroblasts and chondrocytes from four horses and exposed them to fibronectin fragments for 6-18 hours, then analyzed gene expression and protein production patterns. The matrikine stimulation successfully induced an osteoarthritis-like cellular phenotype, with significant increases in key inflammatory markers (IL-1β, IL-6), chemokines (CCL2, CCL5), and cartilage-degrading enzymes (MMP-1, MMP-3, MMP13) that mirror changes seen in human osteoarthritis. This equine matrikine model offers a more physiologically relevant alternative to traditional inflammatory cytokine models and could improve the translation of laboratory findings to clinical treatments, potentially advancing therapeutic development for osteoarthritis management.

A BIOPSYCHOSOCIAL APPROACH TO PHENOTYPING PEOPLE WITH KNEE OSTEOARTHRITIS AWAITING TOTAL KNEE ARTHROPLASTY: A SECONDARY COHORT ANALYSIS.

This study aimed to identify distinct phenotypes in people with knee osteoarthritis awaiting total knee arthroplasty (TKA) using comprehensive biopsychosocial factors, and to examine how these phenotypes relate to post-surgical pain outcomes. The researchers used latent profile analysis on 217 participants from Belgian and Dutch hospitals, analyzing 21 variables including structural damage, physical function, pain characteristics, psychological factors, and social variables.

Two distinct phenotypes were identified: Phenotype 1 (72% of patients) represented those with relatively better overall profiles, while Phenotype 2 (28% of patients) was characterized by higher BMI, less structural damage but worse function, nociplastic pain features (central sensitization, multiple pain sites), and poorer psychological health (higher catastrophizing, anxiety, and depression). Critically, patients in Phenotype 2 experienced significantly worse pain intensity one year after TKA surgery compared to Phenotype 1.

These findings suggest that clinicians should pay special attention to patients presenting with the Phenotype 2 characteristics, as they may be at higher risk for poor post-surgical outcomes and could benefit from targeted preoperative interventions addressing pain sensitization, psychological factors, physical function, and weight management.

LONGITUDINAL STABILITY OF MOLECULAR ENDOTYPES OF KNEE OSTEOARTHRITIS PATIENTS.

This study aimed to evaluate whether biomarker-based molecular endotypes (subgroups) of knee osteoarthritis remain stable over time and could be reliably used for patient classification. Researchers tracked 19 biomarkers in 295 knee osteoarthritis patients over 24 months, using clustering analysis to identify three distinct endotypes: structural damage, inflammation, and low tissue turnover.

The study found that 55% of patients maintained the same endotype classification throughout the follow-up period, with structural damage being the most stable subgroup (59% stability) and low tissue turnover the least stable (50% stability). Patients with unstable endotypes showed molecular characteristics of multiple subgroups from their first visit, suggesting they represent mixed or transitional phenotypes.

These findings suggest that biomarker-based endotyping could be clinically useful for personalizing osteoarthritis management, as more than half of patients have consistent molecular profiles that could guide targeted treatments, though the moderate stability indicates some patients may require reassessment over time.

SURGICAL SIMULATION OF CURVED PERIACETABULAR OSTEOTOMY IN FOUR TYPES OF DEVELOPMENTAL DYSPLASIA OF THE HIP USING FINITE ELEMENT ANALYSIS AND IDENTIFICATION OF THE OPTIMAL ROTATION ANGLE OF THE OSTEOTOMIZED BONE.

This study aimed to determine optimal bone rotation angles for curved periacetabular osteotomy (CPO) surgery across different types of developmental dysplasia of the hip (DDH) to minimize cartilage contact pressure and prevent osteoarthritis progression. The researchers used finite element analysis to simulate CPO surgery on 24 hips from 23 DDH patients, testing various rotation angles (10°-40° lateral rotation, with/without anterior or external rotation) across four distinct DDH phenotypes classified by acetabular deficiency patterns (mild, anterior, posterior, and global types). Key findings revealed that optimal rotation angles varied significantly by DDH type: mild deficiency required 20° lateral rotation, while anterior, posterior, and global types needed 30° lateral rotation (with the latter two also requiring 10° anterior rotation for optimal cartilage contact pressure reduction). These results suggest that CPO surgical planning should be individualized based on specific DDH phenotypes rather than using a one-size-fits-all approach, potentially improving surgical outcomes and long-term joint preservation in DDH patients.

THE IMPACT OF DIFFERENT TYPES OF PHYSICAL ACTIVITY ON THE RISK OF KNEE OSTEOARTHRITIS: A MENDELIAN RANDOMIZATION STUDY.

This Mendelian randomization study aimed to determine whether different types of physical activity have causal relationships with knee osteoarthritis (KOA) risk. The researchers analyzed genetic data from large genome-wide association studies involving over 460,000 individuals for physical activity and 403,000 for KOA, using genetic variants as instruments to assess causality between various activity types and KOA development.

The study found that light do-it-yourself activities and walking for pleasure had significant protective effects against KOA risk, while heavy do-it-yourself work, strenuous sports, other exercises, and physical inactivity showed no statistically significant associations. Notably, the results suggest that activity intensity and type matter more than simply being active versus inactive.

These findings have important implications for physiotherapy practice and public health recommendations, suggesting that low-impact, moderate-intensity activities like walking and light household tasks should be prioritized in KOA prevention strategies rather than high-intensity or strenuous activities.

DEVELOPMENT OF METHODOLOGY TO SUPPORT MOLECULAR ENDOTYPE DISCOVERY FROM SYNOVIAL FLUID OF INDIVIDUALS WITH KNEE OSTEOARTHRITIS: THE STEPUP OA CONSORTIUM.

**Study Summary:**

The STEPUP OA consortium developed a standardized protocol for large-scale protein analysis of synovial fluid to identify molecular subtypes (endotypes) of knee osteoarthritis. The researchers analyzed over 7,000 proteins in 1,746 synovial fluid samples from 1,650 individuals across 17 international cohorts, including people with OA, joint injuries, healthy controls, and inflammatory arthritis, using advanced proteomic technology. Key findings revealed that nearly half of the data variance was related to intracellular proteins (which they controlled for using an "intracellular protein score"), and importantly, OA and injury cases clustered in overlapping but distinguishable patterns within the high-dimensional protein data. This robust methodology creates an unprecedented molecular dataset that could lead to better patient subtyping and personalized treatment approaches, potentially enabling clinicians and physiotherapists to tailor interventions based on individual molecular profiles rather than using one-size-fits-all management strategies.

CELL-INTEGRATED SERUM-INDUCED SIGNALLING PATTERNS CAN DIFFERENTIATE BETWEEN HAND AND KNEE OSTEOARTHRITIS PATIENTS.

This study aimed to identify distinct osteoarthritis (OA) phenotypes by analyzing how patient serum affects cellular signaling pathways, comparing hand OA, knee OA, and healthy individuals. Researchers used 16 specialized cell-based assays to measure pathway activity in serum samples from 55 knee OA patients, 56 hand OA patients, and 42 healthy controls.

The study revealed that hand and knee OA patients have distinctly different serum-induced cellular responses: hand OA serum triggered high MAPK-related activity, while knee OA serum activated pathways related to cartilage formation and immune responses. Additionally, both hand and knee OA groups each split into two distinct subgroups (endotypes), suggesting further biological diversity within each joint location.

These findings indicate that hand and knee OA involve fundamentally different disease mechanisms, which could lead to joint-specific treatment approaches and help explain why therapies may work differently for various OA locations.

DIFFERENCES IN MULTIDIMENSIONAL PHENOTYPE OF 2 JOINT PAIN MODELS LINK EARLY WEIGHT-BEARING DEFICIT TO LATE DEPRESSIVE-LIKE BEHAVIOR IN MALE MICE.

This study aimed to compare how two different joint pain conditions affect pain, function, and mood symptoms in mice, and to identify early predictors of long-term emotional problems. Researchers used mouse models of ankle inflammation and knee osteoarthritis, testing pain sensitivity, weight-bearing function, depression-like behaviors, and brain signaling over 3 months. While both conditions caused similar long-lasting pain sensitivity, only the knee osteoarthritis model led to significant functional deficits (difficulty bearing weight) and emotional symptoms including sleep disruption, cognitive problems, and depression-like behavior. The findings suggest that early weight-bearing problems strongly predict which patients will develop depression and persistent pain later, indicating that physiotherapists and clinicians could use simple functional assessments to identify high-risk patients who need early intervention to prevent emotional complications and improve long-term pain management.

BEYOND THE HIP: CLINICAL PHENOTYPES OF HIP OSTEOARTHRITIS ACROSS THE BIOPSYCHOSOCIAL SPECTRUM.

This study aimed to identify distinct clinical phenotypes of hip osteoarthritis using a comprehensive biopsychosocial approach in 143 patients awaiting hip replacement surgery. Researchers used decision tree learning and cluster analysis to analyze multiple factors including biomedical, psychological, and social variables, with outcomes measured by hip-specific disability scores and pain ratings.

The analysis identified two distinct phenotypes: an "adaptive" phenotype (66% of patients) and a "maladaptive" phenotype (34% of patients) characterized by more comorbidities, lower self-efficacy, and higher levels of anxiety, depression, fear-avoidance behaviors, and feelings of injustice, along with greater pain and disability. Importantly, patients could be accurately classified into these phenotypes (87.8% accuracy) using just two simple clinical tools: the Fear-Avoidance Components Scale and the anxiety subscale of the Hospital Anxiety and Depression Scale.

These findings suggest that clinicians can use brief screening tools to identify hip osteoarthritis patients who may benefit from targeted interventions addressing psychological factors like fear-avoidance and anxiety, potentially leading to more personalized physiotherapy and rehabilitation approaches before and after surgery.

ER STRESS-INDUCED YAP UPREGULATION LEADS TO CHONDROCYTE PHENOTYPE LOSS IN AGE-RELATED OSTEOARTHRITIS.

This study investigated how age-related cellular stress contributes to cartilage breakdown in osteoarthritis by examining the role of YAP protein in chondrocyte (cartilage cell) dysfunction. The researchers analyzed cartilage samples from patients of different ages and used genetically modified mice with YAP overexpression, testing a potential therapeutic drug called pamrevlumab.

The key findings revealed that aging tissues showed increased cellular stress markers and YAP protein levels, and that YAP overexpression caused cartilage cells to lose their normal characteristics and behave more like bone cells, leading to cartilage degeneration similar to osteoarthritis. However, treatment with pamrevlumab successfully prevented this harmful transformation and protected against cartilage breakdown in the modified mice.

These results suggest that age-related osteoarthritis may represent a distinct phenotype driven by specific molecular pathways involving cellular stress and YAP protein signaling. For clinical practice, this research points toward potential new therapeutic targets and indicates that treatments focusing on this stress-YAP pathway, such as pamrevlumab, could offer promising approaches for preventing or treating age-related osteoarthritis in older patients.

EXPLORING THE CORRELATION BETWEEN KNEE OSTEOARTHRITIS AND MUSCULOSKELETAL ULTRASOUND MANIFESTATIONS BASED ON CHANGES IN TRADITIONAL CHINESE MEDICAL SYNDROME TYPES.

This study investigated whether Traditional Chinese Medicine (TCM) syndrome classifications of knee osteoarthritis patients correlate with specific ultrasound features that could guide personalized treatment approaches. Researchers analyzed ultrasound findings in 104 knee osteoarthritis patients categorized into four TCM syndrome types: wind-cold-damp obstruction, damp-heat accumulation, qi-stagnation and blood stasis, and liver and kidney deficiency.

The key findings revealed distinct ultrasound patterns among TCM subgroups: patients with liver and kidney deficiency showed reduced synovial blood flow compared to damp-heat and wind-cold-damp groups, while damp-heat and qi-stagnation patients had more joint effusion than the other subgroups. Importantly, cartilage damage and synovial thickening were similar across all groups, suggesting these TCM phenotypes may reflect different inflammatory and vascular processes rather than structural severity.

These findings suggest that ultrasound imaging could help clinicians identify osteoarthritis subgroups with different underlying pathophysiological mechanisms, potentially enabling more targeted physiotherapy and management strategies based on whether patients present with predominantly inflammatory (high blood flow/effusion) or degenerative (low blood flow) patterns.

GLUTATHIONE HAS CELL PROTECTIVE AND ANTI-CATABOLIC EFFECTS IN ARTICULAR CARTILAGE WITHOUT IMPAIRING THE CHONDROANABOLIC PHENOTYPE.

This study investigated whether direct glutathione (GSH) application could provide better antioxidant therapy than N-acetylcysteine (NAC) for preventing post-traumatic osteoarthritis while preserving cartilage regeneration capacity. Researchers used a drop-tower impact model on porcine cartilage explants and 3D pellet cultures of chondrocytes to compare the effects of GSH (0.5-2mM) versus NAC (2mM) over 4-28 days.

Both antioxidants demonstrated cell-protective effects and reduced matrix degradation (MMP-2 activity) after cartilage trauma, but GSH at 0.5mM concentration preserved the chondrogenic phenotype - maintaining cell proliferation and hyaline cartilage matrix synthesis - while NAC significantly impaired these regenerative processes.

These findings suggest that different antioxidant therapies may define distinct post-traumatic OA phenotypes: one where cellular protection comes at the cost of impaired repair capacity (NAC), versus another where protection and regeneration are both preserved (low-dose GSH), potentially informing targeted rehabilitation strategies for acute joint injuries.

DISEASE MODIFYING OSTEOARTHRITIS DRUG DISCOVERY USING A TEMPORAL PHENOTYPIC REPORTER IN 3D AGGREGATES OF PRIMARY HUMAN CHONDROCYTES.

This study aimed to develop a new method for discovering disease-modifying osteoarthritis drugs by identifying compounds that stimulate type II collagen production in cartilage cells. The researchers used an innovative approach combining genetically modified human chondrocytes (cartilage cells) that could report collagen production in real-time, cultured in 3D lab conditions that mimic natural cartilage, to screen a library of natural compounds over three weeks.

The key finding was that a compound called aromoline significantly increased type II collagen production in cartilage samples from three different donors, working through a previously unknown pathway involving the dopamine receptor D4 (DRD4). This discovery is notable because aromoline had never been tested for cartilage repair before, and the dopamine receptor represents a completely new target for osteoarthritis treatment.

The implications for osteoarthritis management are promising, as this research provides both a new drug candidate (aromoline) and a novel therapeutic target (DRD4 receptor) that could potentially slow or reverse cartilage breakdown, though further research is needed before clinical applications in physiotherapy or medical treatment.

EFFECTS OF THREE TYPES OF RESISTANCE TRAINING ON KNEE OSTEOARTHRITIS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS.

This systematic review and network meta-analysis compared three types of resistance training—isometric (IMMS), isokinetic (IKMS), and isotonic (ITMS) muscle strengthening—for their effectiveness in treating knee osteoarthritis symptoms. The researchers conducted a comprehensive search through September 2023 and analyzed randomized controlled trials comparing these resistance training modalities with conventional physiotherapy or with each other. The key finding was that isokinetic muscle strengthening (IKMS) demonstrated superior outcomes compared to conventional physiotherapy, showing the greatest improvements in pain relief, functional capacity, and quadriceps strength among all three resistance training types. These results suggest that clinicians should consider prioritizing isokinetic training protocols when designing resistance exercise programs for knee osteoarthritis patients, though all three resistance training approaches showed benefits over conventional physiotherapy alone.

ANDROGRAPHOLIDE SUPPRESSES FIBROGENIC PHENOTYPE OF CHONDROCYTES AND AMELIORATES OSTEOARTHRITIS BY REGULATING MIR-137/BMP7 AXIS.

This study investigated how the miR-137/BMP7 molecular pathway contributes to the development of fibrotic cartilage in osteoarthritis (OA) and whether the natural compound andrographolide could provide therapeutic benefits. Researchers analyzed cartilage samples from OA patients versus healthy controls, used laboratory cell models with inflammatory stimulation, and tested andrographolide treatment in an animal OA model. The key finding was that OA cartilage showed reduced levels of miR-137 (a regulatory molecule) and increased BMP7 expression, which was associated with chondrocytes developing a fibrotic phenotype - essentially becoming scar-like tissue rather than healthy cartilage. The results suggest that andrographolide may offer a potential therapeutic approach for OA by restoring normal miR-137/BMP7 balance and preventing harmful cartilage fibrosis, though clinical translation would require further research to determine optimal dosing, delivery methods, and patient selection criteria for rehabilitation programs.

SYNOVIAL FLUID-DERIVED EXOSOMES FROM OSTEOARTHRITIS PATIENTS MODULATE CELL SURFACE PHENOTYPES OF MONOCYTES AND CYTOKINE SECRETIONS.

This study investigated how exosomes (tiny particles) found in knee joint fluid from osteoarthritis patients affect immune cells called monocytes. Researchers isolated exosomes from synovial fluid and exposed them to monocytes in laboratory conditions, then measured changes in cell surface markers and inflammatory molecule production using flow cytometry and ELISA techniques. The key finding was that these exosomes altered monocyte behavior by reducing certain surface markers (HLA-DR, CD14, CD11B) and promoting the release of anti-inflammatory molecules (IL-1RA) in a dose- and time-dependent manner, while not affecting pro-inflammatory TNF-α levels. These results suggest that exosomes in osteoarthritic joints may have a protective, anti-inflammatory role, which could inform future therapeutic approaches and help explain why some osteoarthritis patients may have different inflammatory responses that could influence their rehabilitation outcomes.

SLIDING HYDROGELS REVEAL THE MODULATION OF MECHANOSENSING ATTENUATES THE INFLAMMATORY PHENOTYPE OF OSTEOARTHRITIC CHONDROCYTES IN 3D.

This study investigated how mechanical properties of the cartilage matrix influence the inflammatory behavior of osteoarthritic chondrocytes using a novel 3D hydrogel system. The researchers used "sliding hydrogels" to create environments with varying mechanical compliance and examined how osteoarthritic cartilage cells responded through gene expression analysis, live cell imaging, and mechanosensing pathway assessment.

The key finding was that more compliant (softer) matrix environments significantly reduced the inflammatory phenotype of osteoarthritic chondrocytes by decreasing inflammatory markers and allowing greater cellular movement, while stiffer environments promoted inflammation. The study revealed that this occurs through specific cellular mechanisms involving nuclear signaling pathways and changes in how cells sense and respond to mechanical forces.

These findings suggest that targeting the mechanical environment and mechanosensing pathways could offer new therapeutic approaches for osteoarthritis, potentially informing physiotherapy strategies that optimize joint loading and movement patterns to create more favorable mechanical conditions for cartilage health.

DISTINCT KNEE PHENOTYPE VARIATION: A COMPARATIVE ANALYSIS OF MEDIAL AND LATERAL UNICOMPARTMENTAL KNEE ARTHROPLASTY.

This study aimed to compare knee alignment patterns (phenotypes) between patients who received medial versus lateral unicompartmental knee arthroplasty (UKA) using the Coronal Plane Alignment of the Knee (CPAK) classification system. The researchers retrospectively analyzed 310 knees from 244 patients using EOS imaging to measure hip-knee-ankle alignment, femoral angle, and tibial angle before and after surgery.

The study found distinct phenotype differences between the two groups: medial UKA patients predominantly had varus (inward-angled) knees preoperatively (53.8% Type I), while lateral UKA patients mainly had valgus (outward-angled) knees (77.4% Type III). Importantly, only about one-third of patients maintained their original knee alignment pattern after surgery, with most knees shifting toward neutral alignment regardless of which compartment was replaced.

These findings suggest that different osteoarthritis phenotypes may require compartment-specific surgical approaches, and the CPAK classification could help surgeons and physiotherapists develop more personalized treatment plans by better understanding how knee alignment changes following UKA surgery.

SPATIOTEMPERAL DYNAMICS OF OSTEOARTHRITIS: BRIDGING INSIGHTS FROM BENCH TO BEDSIDE.

This review examines how advanced spatiotemporal analysis technologies can improve our understanding of osteoarthritis (OA) complexity and support personalized treatment approaches. The authors synthesize recent developments in state-of-the-art technologies that enable detailed phenotyping of OA's spatial and temporal variations, from molecular and cellular changes to tissue and joint structure alterations. Key findings highlight that these technological advances provide unprecedented insights into disease progression patterns and reveal patient-specific clinical presentations that reflect OA's diverse phenotypes and underlying biological mechanisms (endotypes). The implications suggest these spatiotemporal phenotyping approaches could transform clinical practice by enabling earlier diagnosis, better understanding of disease pathophysiology, and development of tailored therapeutic strategies that ultimately improve patient outcomes in musculoskeletal rehabilitation.

FOXC1 ACTIVATES NOTCH3 SIGNALING TO PROMOTE THE INFLAMMATORY PHENOTYPE OF KELOID FIBROBLASTS AND AGGRAVATES KELOID.

I notice there may be a mismatch between your request and the provided abstract. You've asked for a summary focused on osteoarthritis phenotyping and musculoskeletal rehabilitation, but this study is about keloid scars (abnormal wound healing), not osteoarthritis.

Here's a summary of the actual study:

This study investigated the molecular mechanisms behind keloid formation, specifically examining how FOXC1 and NOTCH3 proteins contribute to pathological scarring. Researchers used tissue analysis, cell culture experiments with lentiviral gene modification, and molecular binding assays to examine keloid fibroblasts and tissue samples. The key finding was that FOXC1 directly activates NOTCH3 signaling, which promotes an inflammatory phenotype in keloid fibroblasts - increasing their proliferation, migration, and production of scar-forming proteins like collagen and fibronectin. This discovery identifies FOXC1 and NOTCH3 as potential therapeutic targets for preventing or treating keloid scars, though this research doesn't directly relate to osteoarthritis management or musculoskeletal physiotherapy.

Would you like me to provide a different summary, or did you perhaps intend to share a different abstract related to osteoarthritis?

REGULATION OF FIBROBLAST PHENOTYPE IN OSTEOARTHRITIS USING CDKN1A-LOADED COPPER SULFIDE NANOPARTICLES DELIVERED BY MESENCHYMAL STEM CELLS.

This study investigated whether mesenchymal stem cells (MSCs) delivering copper sulfide nanoparticles loaded with CDKN1A gene therapy could regulate harmful fibroblast activity in osteoarthritis. The researchers used single-cell RNA sequencing to identify fibroblast subpopulations in osteoarthritis joints, then developed a nanoparticle delivery system (MSCs@CuS@CDKN1A) and tested it in cell cultures and a mouse model of osteoarthritis.

The treatment successfully modulated fibroblast phenotypes, reducing their inflammatory and tissue-damaging characteristics while improving chondrocyte (cartilage cell) survival and function. In the mouse model, treated joints showed significantly reduced bone spur formation, better joint space preservation, improved cartilage integrity, and lower disease severity scores compared to controls.

These findings suggest that targeting specific fibroblast subpopulations represents a promising therapeutic approach for osteoarthritis, as these cells contribute significantly to joint inflammation and cartilage breakdown. For clinical practice, this research supports the potential development of targeted cell-based therapies that could complement existing physiotherapy and rehabilitation strategies by addressing the underlying cellular mechanisms driving osteoarthritis progression.

EFFECTS OF DIFFERENT TYPES OF TAI CHI INTERVENTION ON MOTOR FUNCTION IN OLDER ADULTS: A SYSTEMATIC REVIEW.

This systematic review aimed to compare the effectiveness of different Tai Chi styles on motor function in older adults with functional impairments across various conditions including osteoarthritis, Parkinson's disease, cognitive impairment, and fall risk. The researchers analyzed 14 studies from five databases, examining Yang-style, Sun-style, Chen-style, and simplified-style Tai Chi interventions and their effects on balance, gait, mobility, strength, and fall rates. The review found that Yang-style Tai Chi was the most commonly used and showed the strongest evidence for improving motor function across different patient subgroups with functional limitations. For clinical practice, the authors recommend Yang-style 24-movement Tai Chi performed 2-5 times weekly for 60 minutes over 12 weeks, with outcomes assessed using standardized tests including single-leg stance, six-minute walk test, timed up-and-go, chair stand test, and fall efficacy scale.

UNDERSTANDING HIP CONTACT STRESS BASED ON TYPES OF PHYSICAL ACTIVITY: A SYSTEMATIC REVIEW.

This systematic review aimed to comprehensively examine how different types of physical activities affect hip contact stress, which is a key risk factor for developing hip osteoarthritis. The researchers conducted a PRISMA-guided systematic review, screening 7,972 papers and ultimately analyzing 21 studies that measured hip contact stress, force, or pressure during various physical activities.

The findings revealed that more intense physical activities, particularly running and stair climbing, generate significantly higher hip contact stress values compared to less demanding activities. However, the reviewed studies showed considerable variation in their methodological approaches, indicating this research area lacks standardization and remains under-investigated.

These results suggest that activity intensity should be carefully considered when developing rehabilitation programs for individuals at risk of hip osteoarthritis, with potential implications for prescribing graded exercise progressions that balance therapeutic benefits while minimizing excessive joint loading.

CD34HI SUBSET OF SYNOVIAL FIBROBLASTS CONTRIBUTES TO FIBROTIC PHENOTYPE OF HUMAN KNEE OSTEOARTHRITIS.

This study aimed to identify specific synovial cell subsets responsible for different osteoarthritis (OA) disease patterns using comprehensive single-cell analysis of human knee synovium samples. The researchers used RNA sequencing and single-cell RNA sequencing to analyze synovial tissue from OA patients, examining gene expression profiles and cellular characteristics.

The key finding was the identification of two distinct OA phenotypes: an inflammatory group characterized by high cytokine expression, tissue inflammation, and more severe pain; and a fibrotic group featuring elevated growth factors (FGFs and BMPs), perivascular fibrosis, and lower pain scores. Specific cell subsets were linked to each phenotype - MERKLO macrophages associated with inflammation, while CD34HI fibroblasts (particularly CD34HICD70HI subsets) contributed to the fibrotic pattern and appeared to suppress inflammation while protecting cartilage.

These findings suggest that OA patients may benefit from phenotype-specific treatment approaches, with inflammatory cases potentially requiring anti-inflammatory interventions while fibrotic cases might need different therapeutic strategies targeting fibroblast activity and tissue remodeling.

KNEE PHENOTYPES DISTRIBUTION ACCORDING TO CPAK CLASSIFICATION IN TURKISH POPULATION.

This study investigated how different knee alignment patterns (CPAK phenotypes) are distributed in the Turkish population by analyzing knee X-rays from 1,172 healthy individuals and 571 people with osteoarthritis. Researchers used specialized imaging software to measure hip-knee-ankle angles and joint-line positioning, categorizing knees into 9 distinct alignment subgroups based on these measurements. The findings revealed that CPAK Type IV (neutral alignment) was most common in both groups (47% healthy, 57% osteoarthritic), followed by Type I, while the "ideal" Type V alignment targeted by traditional surgical approaches was found in less than 8% of both populations. These results suggest that the majority of Turkish knees have natural alignment variations that differ from conventional "ideal" targets, which has important implications for personalizing knee replacement surgery and developing population-specific rehabilitation strategies rather than using one-size-fits-all approaches.

MULTIDIMENSIONAL ANALYSIS OF PREOPERATIVE PATIENT-REPORTED OUTCOMES IDENTIFIES DISTINCT PHENOTYPES IN TOTAL KNEE ARTHROPLASTY: SECONDARY ANALYSIS OF THE SHARKS REGISTRY IN A PUBLIC HOSPITAL DEPARTMENT.

This study aimed to identify distinct patient phenotypes among total knee arthroplasty (TKA) candidates using preoperative patient-reported outcome measures to better understand patient variation and inform clinical decision-making. Researchers analyzed data from 389 patients (450 knees) in a clinical registry between 2017-2021, using k-means clustering on Veterans RAND-12 and Oxford Knee Score data to identify patient subgroups and examining their associations with demographics.

The analysis revealed four distinct phenotypes: patients with mild symptoms and good mental health (best overall function), those with severe symptoms and poor mental health (worst pain and health issues), patients with moderate symptoms but good mental health (high mental health despite physical impairment), and a fourth group with intermediate characteristics. Patients in the severe symptoms/poor mental health phenotype were significantly more likely to be younger, female, have higher BMI, and bilateral osteoarthritis.

These findings suggest that TKA candidates can be meaningfully categorized into phenotypes that combine physical symptoms with mental health status, which could help clinicians tailor preoperative counseling, optimize patient selection, and potentially customize rehabilitation approaches based on individual risk profiles.

ASSOCIATION OF RADIOGRAPHIC STRUCTURE DEFORMITY PHENOTYPES OF KNEE OA TO CLINICAL SYMPTOMS AND RISK FOR PROGRESSION: PROPOSING A MODIFICATION OF KELLGREN-LAWRENCE GRADE - DATA FROM THE OSTEOARTHRITIS INITIATIVE AND THE MOST STUDY.

This study aimed to refine the Kellgren-Lawrence grading system by identifying distinct structural phenotypes within early knee osteoarthritis and examining their clinical implications. Using decision tree analysis on 10,804 knees from two large cohorts (OAI and MOST studies), researchers subdivided KLG1 and KLG2 into joint space narrowing-dominant (JT) versus osteophyte-dominant (OST) phenotypes based on OARSI grading criteria.

The analysis revealed four early OA phenotypes: KLG1OST (single osteophyte without joint space narrowing), KLG1JT (joint space narrowing without osteophytes), KLG2OST (multiple osteophytes without joint space narrowing), and KLG2JT (joint space narrowing with osteophytes). While pain and function were similar between phenotypes within the same KLG, progression rates to advanced OA differed significantly—osteophyte-dominant phenotypes showed substantially slower progression, with KLG1OST progressing 1.87 times slower than KLG1JT, and KLG2OST progressing 5.42 times slower than KLG2JT.

These findings suggest that structural phenotyping could improve prognostic accuracy and potentially guide more personalized treatment approaches

REGULATION OF SENESCENCE-ASSOCIATED SECRETORY PHENOTYPES IN OSTEOARTHRITIS BY CYTOSOLIC UDP-GLCNAC RETENTION AND O-GLCNACYLATION.

This study investigated how cellular sugar metabolism contributes to cartilage breakdown in osteoarthritis by examining the role of UDP-GlcNAc (a cellular sugar compound) in promoting inflammatory aging processes in cartilage cells. The researchers used mouse models of post-traumatic osteoarthritis and analyzed cartilage samples to track changes in sugar transport, protein modifications, and inflammatory signaling pathways.

The key finding revealed that osteoarthritic cartilage has impaired sugar transport systems, causing UDP-GlcNAc to accumulate inside cells where it triggers a cascade leading to increased inflammation through stabilization of the GATA4 protein, particularly in the superficial cartilage layer. When researchers blocked this pathway by deleting GATA4 or inhibiting the responsible enzymes, they successfully reduced cartilage damage and inflammation in the mouse models.

These findings suggest that osteoarthritis patients may have distinct metabolic phenotypes based on their cartilage sugar metabolism patterns, potentially identifying subgroups who might benefit from targeted metabolic interventions. For clinical management, this research indicates that supplements like glucosamine may actually worsen joint damage by promoting this harmful pathway, and points toward developing new treatments that target cellular sugar metabolism to reduce chronic joint inflammation and slow osteoarthritis progression.

CORRECTION TO "ULTRASMALL PRUSSIAN BLUE NANOZYME ATTENUATES OSTEOARTHRITIS BY SCAVENGING REACTIVE OXYGEN SPECIES AND REGULATING MACROPHAGE PHENOTYPE".

I cannot provide a meaningful summary of this study as the abstract is listed as "NA" (not available). This appears to be a correction notice to a previously published article about Prussian blue nanozymes for osteoarthritis treatment, but without access to the actual abstract or correction details, I cannot determine the study's objectives, methods, findings regarding phenotypes/subgroups, or clinical implications for musculoskeletal rehabilitation and physiotherapy practice.

To provide an accurate summary focusing on osteoarthritis phenotyping and rehabilitation implications, I would need access to either the original article's abstract or the specific correction details.

DEEP LEARNING-BASED CLUSTERING FOR ENDOTYPING AND POST-ARTHROPLASTY RESPONSE CLASSIFICATION USING KNEE OSTEOARTHRITIS MULTIOMIC DATA.

This study aimed to identify distinct knee osteoarthritis (KOA) patient subgroups using molecular data from multiple body fluids and predict pain/function outcomes one year after total knee replacement surgery. The researchers analyzed plasma, synovial fluid, and urine samples from 414 KOA patients using advanced sequencing and metabolomics techniques, then applied a sophisticated deep learning approach to integrate microRNAs and metabolites across all fluid types.

The analysis identified three distinct patient clusters, each characterized by unique molecular signatures involving 16-30 specific microRNAs and metabolites, with different biological pathways active in each subgroup. Importantly, combining molecular data from multiple fluids with clinical information significantly improved the ability to predict which patients would have better pain relief and functional improvement after knee replacement surgery compared to using any single type of data alone.

These findings suggest that KOA patients can be classified into biologically distinct subgroups based on their molecular profiles, which could help clinicians better predict surgical outcomes and potentially tailor treatment approaches, representing an important step toward personalized medicine in osteoarthritis management.

ANTIDEPRESSANTS TO MANAGE OSTEOARTHRITIC PAIN: THE VALUE OF PAIN PHENOTYPING.

This review examines the potential of pain phenotyping to improve antidepressant treatment selection for osteoarthritis (OA) pain management. The authors highlight that current OA pain treatments have limited success partly due to insufficient recognition of patient heterogeneity, including psychosocial factors like anxiety and depression that can worsen pain experiences. The key finding is that while antidepressants, particularly SNRIs, show promise for treating both psychological symptoms and OA pain, their effectiveness varies significantly between individuals. The authors conclude that developing standardized pain phenotyping methods could enable more personalized antidepressant prescribing, potentially improving treatment efficacy and reducing side effects - an approach that could complement physiotherapy by better addressing the psychological components of OA pain management.

THE INFLUENCE OF KNEE PHENOTYPES BASED ON CORONAL PLANE ALIGNMENT OF THE KNEE ON INTRAOPERATIVE SOFT TISSUE BALANCE AND CLINICAL OUTCOMES: COMPARISON BETWEEN KINEMATICALLY AND MECHANICALLY ALIGNED TOTAL KNEE ARTHROPLASTY.

This study investigated how preoperative knee alignment patterns (using the Coronal Plane Alignment of the Knee [CPAK] classification) influence surgical outcomes when comparing two different total knee replacement techniques: modified kinematically aligned (MKA) and mechanically aligned (MA) approaches. The researchers analyzed 153 knees, measuring intraoperative soft tissue balance and comparing clinical outcomes including range of motion and knee scores at one year post-surgery.

The key finding was that CPAK Type I knees (constitutionally varus alignment) responded better to the MKA technique, showing preserved lateral laxity during knee bending, improved range of motion, and higher patient satisfaction scores compared to both Type II knees with MKA and Type I knees with traditional MA surgery. Type I knees treated with MKA maintained more natural varus balance patterns throughout different degrees of knee flexion, particularly in mid- and deep flexion ranges.

These results suggest that preoperative knee alignment phenotyping using CPAK classification could guide surgical decision-making, with constitutionally varus knees (Type I) potentially benefiting more from kinematically aligned techniques that preserve their natural alignment patterns rather than forcing them into a mechanically neutral position.

MACROPHAGE PHENOTYPES MODULATE NEOANGIOGENESIS AND FIBROBLAST PROFILES IN SYNOVIAL-LIKE ORGANOID CULTURES.

This study aimed to investigate how different macrophage types influence inflammation, blood vessel formation, and tissue scarring in synovial tissue by creating laboratory models that mimic the joint lining. The researchers used 3D cell cultures containing fibroblasts, different types of macrophages (pro-inflammatory and anti-inflammatory), and endothelial cells, then analyzed gene expression, protein secretion, and blood vessel development over time.

The key finding was that macrophage phenotypes created distinct patterns of tissue response: pro-inflammatory macrophages caused peak blood vessel formation around day 21, while anti-inflammatory macrophages sustained this process longer and influenced genes related to tissue scarring and blood vessel growth. When the researchers added particles that mimic joint replacement wear debris, they could observe how different materials trigger local inflammatory reactions.

These results suggest that targeting specific macrophage populations could be important for managing chronic synovial inflammation in osteoarthritis and after joint replacement surgery, potentially informing physiotherapy timing and anti-inflammatory treatment strategies.

GENDER-DIFFERENCES IN IMAGING PHENOTYPES OF OSTEOARTHRITIS IN THE OSTEOARTHRITIS INITIATIVE.

This study investigated whether gender differences in osteoarthritis (OA) clinical presentation extend to distinct imaging-based disease patterns. The researchers analyzed 3T MRI scans and whole-organ MRI scores from 2,523 participants in the Osteoarthritis Initiative, classifying knees into three imaging phenotypes: inflammatory, meniscus-cartilage, and bone phenotypes using modified scoring systems. The key finding was that women had significantly lower odds of having the meniscus-cartilage phenotype compared to men, while showing no significant gender differences in inflammatory or bone phenotypes. These results suggest that gender-specific imaging phenotypes should be considered when developing personalized treatment approaches and rehabilitation strategies for knee OA, potentially leading to more targeted physiotherapy interventions based on the underlying structural patterns of disease.

THE ROLE OF MATN3 IN CANCER PROGNOSIS AND IMMUNE INFILTRATION ACROSS MULTIPLE TUMOR TYPES.

This study does not appear to be related to osteoarthritis phenotyping or musculoskeletal rehabilitation research. The objective was to investigate the role of MATN3 (a matrix protein) as a prognostic biomarker across 33 different cancer types using multiple databases and experimental validation. The researchers used bioinformatics analyses of cancer databases, survival analysis, and laboratory experiments to examine MATN3 expression, immune infiltration patterns, and cellular functions. The main findings showed that MATN3 is overexpressed in most cancers and associated with poorer prognosis, while experimental silencing of MATN3 reduced cancer cell proliferation, migration, and invasion. This research has no direct implications for osteoarthritis management or physiotherapy, as it focuses entirely on cancer biology rather than musculoskeletal conditions.

CLINICAL PHENOTYPES AND ASSOCIATED FACTORS IN KNEE OSTEOARTHRITIS IN AN AFRICAN BLACK POPULATION.

This study aimed to identify clinical phenotypes of knee osteoarthritis in a black Sub-Saharan African population using data from 321 patients (mean age 58.7 years, 81% female) collected over one year in a rheumatology department. The researchers used K-means clustering analysis to identify distinct patient subgroups and logistic regression to determine factors associated with each phenotype.

Five distinct clinical phenotypes were identified: "osteoporotic" (47% of patients), "metabolic" (35%), "genetic" (5%), "biomechanical" (7%), and "post-traumatic" (5%). The osteoporotic phenotype was significantly more common in women and patients over 60 years old, while the post-traumatic phenotype was more frequent in younger patients (<60 years) with tibiofemoral osteoarthritis.

These findings suggest that knee osteoarthritis presents as distinct clinical subgroups in this population, with age, sex, and joint location being key differentiating factors. This phenotyping approach could inform personalized treatment strategies, with older women potentially requiring osteoporosis management alongside standard osteoarthritis care, while younger patients with post-traumatic phenotypes may benefit from biomechanically-focused physiotherapy interventions.

MSCS-EVS HARBORING OA IMMUNE MEMORY REPROGRAM MACROPHAGE PHENOTYPE VIA MODULATION OF THE MT-ND3/NADH-COQ AXIS FOR OA TREATMENT.

This study aimed to develop an enhanced cell therapy approach for osteoarthritis by engineering mesenchymal stem cell-derived extracellular vesicles (MSCs-EVs) with "immune memory" to better target OA inflammation. The researchers primed MSCs with inflammatory factors that mimic the OA joint environment (particularly IL-6), then analyzed the resulting vesicles using proteomic analysis and tested their effects on immune cells both in laboratory and animal models.

The key finding was that IL-6-primed vesicles effectively reprogrammed inflammatory macrophages toward a healing-promoting M2 phenotype, reducing joint inflammation and slowing OA progression. This therapeutic effect worked through a specific cellular pathway (MT-ND3/NADH-CoQ axis) that regulates energy production in mitochondria.

These results suggest that engineered MSC-derived vesicles could offer a more targeted and effective treatment approach for OA patients, potentially providing better outcomes than current stem cell therapies by specifically addressing the inflammatory processes that drive joint degeneration.

INTERSTITIAL CYSTITIS: A PHENOTYPE AND RARE VARIANT EXOME SEQUENCING STUDY: INTERSTITIAL CYSTITIS: A PHENOTYPE AND EXOME SEQUENCING STUDY.

This study investigated the genetic basis and clinical associations of interstitial cystitis/bladder pain syndrome (IC/BPS) using large-scale medical records and genetic sequencing data. The researchers analyzed phenotypic patterns in patients with IC/BPS and conducted exome sequencing on 348 IC/BPS cases compared to nearly 12,000 controls to identify rare genetic variants.

The study confirmed known associations between IC/BPS and conditions like irritable bowel syndrome, while discovering new links including osteoarthritis and Barrett's esophagus, suggesting IC/BPS may be part of a broader multi-system disorder. Genetic analysis revealed that IC/BPS is associated with rare variants in genes related to skin integrity and cell cycle regulation, rather than the previously suspected pathways involving bladder development or inflammation.

These findings suggest IC/BPS involves disrupted epithelial barrier function and cellular processes across multiple organ systems. For clinicians, this research highlights the importance of screening IC/BPS patients for comorbid conditions like osteoarthritis, and suggests that management approaches addressing systemic epithelial integrity may be more effective than treatments focused solely on bladder-specific mechanisms.

THREE-COMPARTMENT PHENOTYPE CONCEPT OF TOTAL KNEE ARTHROPLASTY ALIGNMENT: MISMATCH BETWEEN DISTAL FEMORAL, POSTERIOR FEMORAL, AND TIBIAL JOINT LINES.

This study aimed to expand the functional knee phenotype (FKP) concept by examining whether patients with different coronal (side-to-side) alignment variations also have distinct rotational alignment patterns, and to assess how often the multiple joint lines of the knee are naturally aligned. The researchers measured rotational angles in 265 non-arthritic knees and 2,692 osteoarthritic knees, categorizing patients into phenotypes based on anterior and posterior femoral joint line alignment, then analyzed how these related to existing coronal phenotypes and different surgical alignment approaches.

The key finding was that natural alignment between all knee joint compartments is rare - only 2.3% of healthy knees had all four joint lines (distal femoral, posterior femoral, anterior femoral, and tibial) properly aligned, with slightly higher rates for partial alignment between some compartments. Importantly, coronal and rotational phenotypes appeared to be independent of each other, suggesting they represent separate anatomical variations.

These findings suggest that preoperative assessment for total knee replacement should include evaluation of both anterior and posterior femoral joint lines, not just the traditional measurements. The extended phenotyping approach could help surgeons identify patients at higher risk for complications due to anatomical mismatches and guide selection of the most appropriate surgical alignment strategy for each individual patient's unique anatomy.

LATENT TRANSITION ANALYSIS OF PAIN PHENOTYPES IN PEOPLE AT RISK OF KNEE OSTEOARTHRITIS: THE MOST COHORT STUDY.

This study aimed to identify distinct pain phenotypes and track their stability over time in people at risk of developing knee osteoarthritis, using data from 348 participants without radiographic knee OA followed for 7 years in the MOST cohort study. Researchers used latent transition analysis to examine multiple pain-related measures including pressure pain thresholds, temporal summation, depression, pain catastrophizing, sleep quality, and widespread pain across three time points.

Three distinct pain phenotypes emerged: low pain burden, high pain sensitization, and high psychological burden, with remarkable stability over time as 86% of participants remained in the same phenotype throughout the study period. These findings suggest that pain phenotypes represent trait-like characteristics that are established early in the disease process, indicating that targeted prevention and management strategies should be tailored to individual phenotypes rather than using a one-size-fits-all approach in physiotherapy and rehabilitation.

THE ROLE OF THE IMMUNE SYSTEM IN OSTEOARTHRITIS: MECHANISMS, CHALLENGES AND FUTURE DIRECTIONS.

This review examined the evolving understanding of immune system involvement in osteoarthritis, moving beyond the traditional "wear-and-tear" model to explore inflammatory and autoimmune mechanisms. The authors synthesized recent research using advanced immunological techniques that have identified diverse immune cell populations in joint tissues, including synovial lymphoid structures, autoantibodies, and altered T and B cell populations. Key findings reveal that OA exhibits features typically associated with autoimmune diseases, and importantly, these immune changes vary across different OA phenotypes, suggesting distinct molecular endotypes that could be used for patient stratification. These insights have significant implications for personalized treatment approaches, as understanding immune-driven OA subgroups could lead to targeted therapies and improved treatment allocation, while also opening new management avenues through addressing systemic factors like gut-joint axis dysfunction.

THE INFLAMMATORY ENDOTYPE IN OSTEOARTHRITIS: REFLECTIONS FROM THE 2024 OARSI CLINICAL TRIALS SYMPOSIUM (CTS) WITH A SPECIAL EMPHASIS ON FEASIBILITY FOR CLINICAL DEVELOPMENT.

This report summarizes discussions from the 2024 OARSI Clinical Trials Symposium focused on examining the feasibility of developing the inflammatory endotype in osteoarthritis for clinical drug development. The symposium brought together diverse stakeholders including regulators, drug developers, clinicians, and researchers to discuss challenges and opportunities in translating this well-established OA subtype into therapeutic applications. The main finding highlighted an ongoing tension between academic research pursuing innovative "blue ocean" strategies and industry's need for feasible, practical approaches to drug development. The authors conclude that successful development of treatments targeting the inflammatory OA phenotype requires multidisciplinary collaboration that balances scientific discovery with regulatory requirements and clinical practicality, which could ultimately lead to more personalized and effective treatments for OA patients.

ASSOCIATION OF KNEE OSTEOARTHRITIS TREATMENT TYPES, PATIENT CHARACTERISTICS, AND MEDICAL HISTORY WITH SUBSEQUENT RISK FOR TOTAL KNEE ARTHROPLASTY: DATA FROM A NEW REAL-WORLD REGISTRY.

This study aimed to identify predictors of total knee arthroplasty (TKA) within 6 months following non-surgical knee osteoarthritis treatments using real-world registry data. The researchers analyzed 505 patients with unilateral knee OA who received various treatments (including nerve blocks, injections of hyaluronic acid, corticosteroids, or anti-inflammatory drugs) and used statistical modeling to identify risk factors for subsequent surgery.

The analysis revealed two distinct high-risk phenotypes for early TKA conversion: patients with obesity and those with severe (Kellgren-Lawrence grade IV) knee osteoarthritis, while surprisingly, factors like age, sex, baseline pain scores, and activity levels were not predictive. Among treatments, intra-articular hyaluronic acid and extended-release triamcinolone injections showed the strongest association with reduced conversion to surgery within 6 months.

These findings suggest that clinicians should prioritize weight management interventions for obese patients and consider that severe radiographic changes (grade IV OA) indicate high surgical risk regardless of other patient characteristics, while certain injection therapies may provide meaningful short-term surgical avoidance for appropriate candidates.

REPROGRAMMING MACROPHAGE PHENOTYPE USING A REACTIVE OXYGEN SPECIES-RESPONSIVE LIPOSOME DELIVERY SYSTEM FOR INFLAMMATION MICROENVIRONMENT REMODELING AND OSTEOARTHRITIS TREATMENT.

This study aimed to develop a targeted drug delivery system to treat osteoarthritis by rebalancing inflammatory macrophage subtypes in joint tissue. The researchers created specialized liposomes (drug carriers) that respond to high levels of reactive oxygen species and specifically target pro-inflammatory M1 macrophages, delivering an anti-inflammatory drug (dimethyl fumarate) to reprogram these cells into anti-inflammatory M2 macrophages.

Laboratory experiments showed the liposomes successfully reduced inflammation markers in M1 macrophages and converted them to the beneficial M2 phenotype through a specific cellular pathway (NRF2/HO-1), which protected cartilage cells from damage and death. In mouse studies using a surgical model of osteoarthritis, the targeted liposome treatment significantly reduced joint inflammation, preserved cartilage, and slowed overall disease progression compared to controls.

This research suggests that targeting specific macrophage phenotypes represents a promising therapeutic approach for osteoarthritis, potentially offering a more precise treatment strategy that addresses the underlying inflammatory processes driving joint degeneration rather than just managing symptoms.

RESTORATION OF ANATOMICAL KNEE PHENOTYPE IS ASSOCIATED WITH IMPROVED POSTOPERATIVE CLINICAL OUTCOMES AFTER TOTAL KNEE ARTHROPLASTY.

This study investigated whether restoring patients' natural knee anatomy during total knee arthroplasty (TKA) leads to better clinical outcomes compared to standard mechanical alignment techniques. The researchers analyzed 1,052 osteoarthritic knees, categorizing patients using the CPAK classification system based on their natural joint line orientation (JLO) and limb alignment, then compared 2-year patient-reported outcomes between those whose knee anatomy was restored versus those where it was not.

Only 12.1% of patients had their natural knee phenotype restored using standard mechanical alignment techniques, but these patients showed significantly better functional outcomes and joint awareness scores compared to the non-restored group. Importantly, restoration of joint line orientation was more critical for good outcomes than overall limb alignment restoration.

These findings suggest that surgical techniques should prioritize maintaining each patient's individual joint line orientation rather than applying a one-size-fits-all mechanical alignment approach, potentially leading to more personalized TKA procedures and improved patient satisfaction with functional outcomes.

BEYOND CORONAL PLANE ALIGNMENT OF THE KNEE: SIMILARITY AND VARIABILITY OF EXTENSION KNEE BALANCE ACROSS CORONAL PLANE ALIGNMENT OF THE KNEE PHENOTYPES.

This study aimed to evaluate how extension knee balance varies across the six different Coronal Plane Alignment of the Knee (CPAK) phenotypes, which are currently used to guide surgical alignment strategies in total knee arthroplasty. The researchers analyzed data from 4,362 robotic knee surgeries, simulating joint space distraction and calculating balance in both arthritic and healthy tissue states while accounting for cartilage wear patterns.

The findings revealed substantial overlap in extension balance between different CPAK phenotypes, with the highest similarity (74-84%) observed between CPAK II (neutral alignment) and IV (varus morphotype), while extreme phenotypes (CPAK I and VI) showed expected differences but still had 6-40% overlap. When cartilage loss was factored into the analysis, similarities between phenotypes increased further, suggesting that the current CPAK classification may not adequately distinguish functional knee characteristics.

These results indicate that the CPAK classification system requires refinement to better account for soft-tissue variability and improve its clinical utility, as current phenotyping based solely on bony alignment may not sufficiently predict knee function or guide individualized treatment approaches in both surgical and non-surgical musculoskeletal rehabilitation.

[BIOMARKERS AND THEIR ROLE IN UNDERSTANDING OSTEOARTHRITIS].

This review aimed to summarize current knowledge about biomarkers in osteoarthritis (OA) and explore their potential for improving early diagnosis and personalized treatment approaches. The authors conducted a narrative review focusing on various types of biomarkers, including radiographic, histological, physiological, and particularly molecular biomarkers, with special attention to knee OA research.

The review highlights that current diagnostic methods (clinical symptoms and radiographic findings) often fail to detect OA in early stages when joint damage is still reversible, leading to delayed diagnosis and reduced effectiveness of conservative treatments. Biomarkers show promise for identifying and predicting early-stage OA before irreversible joint destruction occurs, potentially enabling earlier intervention when treatments are more effective.

For clinical practice and physiotherapy, these findings suggest that biomarker-guided approaches could revolutionize OA management by enabling earlier detection and more personalized treatment strategies, though the review appears to be conceptual rather than presenting specific phenotyping results or direct rehabilitation implications.

ACCELERATED BIOLOGICAL AGING IN PATIENTS WITH DEGENERATIVE SPINE DISEASES: THE IMPACT OF MODIFIABLE LIFESTYLE FACTORS ON PHENOTYPIC AGE.

This study investigated whether patients with degenerative spine diseases (DSD) show accelerated biological aging compared to healthy controls, and examined how lifestyle factors influence this process. The researchers analyzed 10,205 healthy individuals, 397 DSD patients (with adult spinal deformity or lumbar spinal stenosis), and 306 osteoarthritis patients using "phenotypic age" (PhenoAge) - a biomarker-based measure that may better reflect true biological aging than chronological age alone.

Key findings revealed that DSD patients had a 4.2-year elevation in biological age compared to matched controls, along with higher inflammatory markers, suggesting accelerated aging in this population. Importantly, lifestyle factors significantly influenced biological aging: smoking and obesity increased biological age acceleration, while physical activity reduced it, and these effects persisted over a 3-year follow-up period.

These results suggest that clinicians and physiotherapists should prioritize lifestyle interventions targeting smoking cessation, weight management, and physical activity promotion as part of comprehensive care for patients with degenerative spine conditions, as these modifiable factors may help slow biological aging processes and potentially improve overall health outcomes.

MOLECULAR ENDOTYPES AND THERATYPES IN OSTEOARTHRITIS: TRANSFORMING A CONCEPT INTO REALITY WITH DEEP LEARNING AND MULTIOMICS.

I notice that the abstract is listed as "NA" (not available), so I can only work with the title information provided. Based solely on the title, here's what I can infer:

**Study Focus**: This research appears to explore molecular-based classification systems (endotypes and theratypes) in osteoarthritis using advanced computational and multi-biological data approaches. **Methods**: The study likely employs deep learning algorithms combined with multiomics data (potentially including genomics, proteomics, metabolomics, and other biological markers) to identify distinct molecular patterns. **Expected Approach to Phenotyping**: The research presumably aims to move beyond traditional symptom-based classification toward molecular signatures that could define specific osteoarthritis subtypes and treatment-responsive groups. **Potential Clinical Implications**: This molecular approach could potentially enable more personalized treatment strategies and targeted therapeutic interventions, though specific findings and recommendations for physiotherapy management cannot be determined without the full abstract.

*Note: This summary is limited by the unavailable abstract and represents inferences based solely on the title and terminology used.*

CHASING THE TARGET: REPORTS FROM THE ADVANCES IN TARGETED THERAPIES MEETING, 2024.

This report summarized expert discussions at the 2024 Advances in Targeted Therapies meeting, which aimed to identify the most critical unmet scientific needs in rheumatology over the next 5 years. The meeting brought together over 100 international experts who participated in disease-specific discussion groups for rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, osteoarthritis, and systemic lupus erythematosus. Across all conditions, experts identified common themes including the urgent need for precision medicine approaches, better classification of disease subtypes (endotypes), and identification of new therapeutic targets, particularly for difficult-to-treat patients. For osteoarthritis specifically, the key priorities were discovering new therapeutic targets and understanding which specific cells and signaling pathways drive or inhibit tissue repair, which could inform more targeted rehabilitation and treatment strategies for different patient subgroups.

IMPACT OF SPINAL-HIP TYPES ON GAIT PATTERNS IN PATIENTS WITH END-STAGE HIP DISEASE.

This study aimed to characterize how different spinal-hip alignment types affect walking patterns in patients with severe hip disease requiring joint replacement. Researchers used specialized EOS imaging to classify 30 patients into three distinct spinal-hip types (A, B, and C) based on their spine and hip alignment, then compared their gait patterns using 3D movement analysis against 10 healthy controls.

The study revealed that each spinal-hip type demonstrated unique walking adaptations: Type A patients (severe sagittal imbalance) showed the most abnormal gait with increased pelvic movement, restricted hip and knee motion, and the worst overall movement quality scores; Type C patients had the shortest stride length; while Type B patients walked most similarly to healthy individuals.

These findings suggest that patients with end-stage hip disease are not a homogeneous group but rather distinct phenotypes requiring different rehabilitation approaches, with those having spinal-hip imbalance (particularly Type A) likely needing more intensive physiotherapy focused on compensatory movement patterns both before and after hip replacement surgery.

IDENTIFYING CAUSAL BRAIN STRUCTURES, GENES, AND PROTEINS FOR OSTEOARTHRITIS: A LARGE-SCALE GENETIC CORRELATION STUDY BASED ON BRAIN IMAGING-DERIVED PHENOTYPES, TRANSCRIPTOMES, AND PROTEOMES.

This large-scale genetic study aimed to validate brain-osteoarthritis connections and identify causal genes by integrating brain imaging, gene expression, and protein data with osteoarthritis genome-wide association studies from 826,690 participants. The researchers used advanced genetic analysis methods including linkage disequilibrium score regression, Mendelian randomization, and transcriptome/proteome-wide association studies to examine relationships between brain structures and OA risk. Key findings revealed that specific brain regions (putamen and amygdala) are strongly associated with OA, with seven genes linked to knee OA and four to hip OA, plus identification of specific proteins and brain cell types (particularly CPNE1 in excitatory neurons) causally connected to joint degeneration. These results provide new insights into the brain-joint axis in OA development, potentially opening novel therapeutic avenues that target central nervous system pathways rather than focusing solely on joint-based treatments in physiotherapy and rehabilitation approaches.

THE PHENOTYPIC AND GENETIC ASSOCIATION BETWEEN ENDOMETRIOSIS AND IMMUNOLOGICAL DISEASES.

This study investigated whether women with endometriosis have increased risk of immune-related diseases and whether shared genetic factors contribute to this association. The researchers analyzed data from over 72,000 women in the UK Biobank using retrospective cohort and cross-sectional approaches, followed by genome-wide association studies and genetic correlation analyses to identify shared biological pathways between endometriosis and 31 immune conditions.

The findings revealed that women with endometriosis have a 30-80% increased risk of developing autoimmune and inflammatory diseases, particularly osteoarthritis, rheumatoid arthritis, multiple sclerosis, coeliac disease, and psoriasis, with strong genetic correlations identified between endometriosis and osteoarthritis, rheumatoid arthritis, and multiple sclerosis. The study identified shared genetic variants and biological pathways underlying these conditions, with evidence suggesting endometriosis may causally contribute to rheumatoid arthritis development.

For clinical practice, these findings highlight the need for increased awareness among healthcare providers about the elevated risk of musculoskeletal and autoimmune conditions in women with endometriosis, particularly osteoarthritis and rheumatoid arthritis. The shared genetic basis opens opportunities for developing targeted treatments and suggests that physiotherapists managing women with endometriosis should monitor for early signs of joint pain and mobility issues that could indicate developing osteo

RESPONSE TO LETTER TO EDITOR ON "ASSOCIATION OF KNEE OSTEOARTHRITIS TREATMENT TYPES, PATIENT CHARACTERISTICS, AND MEDICAL HISTORY WITH SUBSEQUENT RISK FOR TOTAL KNEE ARTHROPLASTY: DATA FROM A NEW REAL-WORLD REGISTRY".

I apologize, but I cannot provide a meaningful summary of this research paper. The document appears to be a "Response to Letter to Editor" rather than an original research study, and no abstract is provided.

Response letters typically address criticisms, clarifications, or additional perspectives on previously published research rather than presenting new study objectives, methods, findings, or clinical implications. To provide the concise summary you've requested focusing on study objectives, phenotyping methods, subgroup findings, and physiotherapy implications, I would need access to either:

1. The abstract of this response letter, or
2. The original research article that this letter is responding to

If you can provide the abstract or additional content, I'd be happy to create the clinical summary you're looking for.

DISTRIBUTION OF CORONAL PLANE ALIGNMENT OF THE KNEE AND FUNCTIONAL KNEE PHENOTYPE CLASSIFICATION IN THE THAI ARTHRITIC POPULATION AND CORRELATION WITH OTHER ASIAN POPULATIONS.

This study examined the distribution of knee alignment phenotypes in 509 Thai patients undergoing knee arthroplasty using two classification systems: Coronal Plane Alignment of the Knee (CPAK) and Functional Knee Phenotype (FKP), based on long-leg standing radiographs. The research found that Thai arthritic knees predominantly exhibited Type I CPAK (49.3% of patients) with apex distal joint-line obliquity and constitutional varus alignment, with males showing significantly higher rates of Type I alignment than females (58.8% vs 46.5%). The most common FKP patterns were varus configurations, particularly VAR 6°VAR 3°VAR 3° (10% of patients), indicating that Thai patients typically present with varus-aligned knees similar to other Asian populations. These findings support the importance of recognizing population-specific alignment patterns when planning knee arthroplasty, as maintaining constitutional alignment rather than pursuing neutral mechanical alignment may lead to better surgical outcomes and more personalized treatment approaches.

ISOKINETIC KNEE STRENGTH AND PATIENT-REPORTED OUTCOMES DIFFER BETWEEN GRAFT TYPES IN ADOLESCENTS AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION: A MULTICENTER STUDY.

This multicenter study aimed to compare knee strength and patient-reported outcomes between different graft types in 522 adolescents following anterior cruciate ligament reconstruction (ACLR). The researchers used isokinetic strength testing and multiple validated questionnaires to assess outcomes at approximately 8 months post-surgery across three graft types: bone-patellar tendon-bone (BPTB), quadriceps tendon (QT), and hamstring tendon (HT).

The study identified distinct strength phenotypes based on graft type: adolescents with HT grafts showed the best quadriceps strength recovery but the worst hamstring strength, while those with BPTB grafts demonstrated the opposite pattern with poorest quadriceps but best hamstring strength, and QT grafts fell between these extremes. Patient-reported outcomes were mixed, with HT graft patients reporting better overall knee function and sports participation compared to BPTB patients, while psychological readiness to return to sport was similar across all groups.

These findings suggest that graft selection creates predictable strength deficit patterns that should inform targeted rehabilitation strategies—emphasizing quadriceps strengthening for BPTB/QT patients and hamstring strengthening for HT patients in adolescent populations.

EXOSOMES OF HUMAN FETAL CARTILAGE PROGENITOR CELLS (HFCPCS) INHIBITED INTERLEUKIN-1Β (IL-1Β)-INDUCED OSTEOARTHRITIS PHENOTYPE VIA MIR-125B-5P IN VITRO.

This study investigated whether exosomes from human fetal cartilage progenitor cells (hFCPC-exo) could reduce inflammation in laboratory models of osteoarthritis, comparing their effects to exosomes from bone marrow stem cells. Researchers treated joint cells (synoviocytes and chondrocytes) with IL-1β to create an inflammatory osteoarthritis-like environment, then examined how different exosome treatments affected inflammatory markers and tissue breakdown.

The study found that hFCPC-exo effectively reduced inflammatory cytokines and cartilage-degrading enzymes while promoting cartilage repair proteins, with these protective effects primarily mediated by a specific microRNA called miR-125b-5p that blocks inflammatory signaling pathways. Both synoviocytes (joint lining cells) and chondrocytes (cartilage cells) showed similar beneficial responses to the exosome treatment, suggesting the therapy targets multiple cell types involved in osteoarthritis progression.

These findings suggest that exosome-based therapies could potentially offer a new approach for managing osteoarthritis by targeting the underlying inflammatory processes rather than just symptoms. While this is early laboratory research, it indicates that such treatments might complement physiotherapy and other management strategies by helping to preserve cartilage and reduce joint inflammation at the cellular level.

BEYOND SYMPTOMATIC ALIGNMENT: EVALUATING THE INTEGRATION OF CAUSAL MECHANISMS IN MATCHING ANIMAL MODELS WITH HUMAN PATHOTYPES IN OSTEOARTHRITIS RESEARCH.

This review examines how well current animal models represent the diverse underlying disease mechanisms (endotypes) of human osteoarthritis, rather than simply mimicking clinical symptoms. The authors evaluated existing animal models by analyzing their ability to replicate the molecular pathways and pathophysiological processes that drive different OA subtypes in humans, considering factors like age, sex, metabolic status, and comorbidities that influence disease development.

The key finding is that current animal models are inadequate because they focus on superficial symptom matching rather than replicating the specific molecular mechanisms underlying different OA phenotypes, and traditional assessment methods (macroscopic/histological scoring, basic biomarkers) are insufficient for identifying new therapeutic targets.

This has important implications for developing personalized OA treatments - the authors argue that better animal models matching human endotypes are essential for discovering phenotype-specific therapies that could move beyond current symptomatic management to targeted interventions addressing the root molecular causes of different OA subtypes.

FEMORAL VARUS DEFORMITY PREDOMINATES IN MALE CHINESE OSTEOARTHRITIS PATIENTS WITH GEOGRAPHIC VARIABILITY IN FUNCTIONAL KNEE PHENOTYPES.

This study aimed to characterize functional knee phenotypes in Chinese osteoarthritis patients and examine sex and geographic differences in deformity patterns. The researchers analyzed knee alignment measurements (hip-knee-ankle angle, femoral and tibial mechanical angles) in 908 osteoarthritic knees using Hirschmann's classification system, and compared findings with data from 16,395 knees across seven international studies.

The study identified 145 distinct functional knee phenotypes, with Chinese OA patients showing a predominant tendency toward femoral and tibial varus (inward angulation) deformities in both sexes. Notably, femoral varus deformity was more prevalent than tibial varus in 48% of males compared to only 37% of females, indicating important sex-based differences in deformity patterns.

These findings suggest that osteoarthritis management and physiotherapy interventions should consider both sex-specific deformity patterns and geographic variations when developing treatment protocols, as the predominance of femoral versus tibial involvement may influence optimal rehabilitation strategies and surgical planning approaches.

CORONAL PLANE ALIGNMENT OF THE KNEE PHENOTYPES DISTRIBUTION VARIES SIGNIFICANTLY AS A FUNCTION OF GEOGRAPHIC, OSTEOARTHRITIC AND SEX-RELATED FACTORS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

This systematic review and meta-analysis examined how knee alignment patterns, classified using the nine-phenotype Coronal Plane Alignment of the Knee (CPAK) system, vary across different populations and geographic regions. The researchers analyzed 38 studies encompassing 46,966 knees using long-leg radiographs to determine the distribution of alignment phenotypes globally.

The study revealed significant geographic, disease-related, and sex-based differences in knee alignment patterns. In osteoarthritic populations, CPAK Type I (neutral alignment) was most common globally (33.1%), but regional variations existed with Type I predominating in Europe, Asia, and America, while Type II was most common in Australia and Type III in Africa. Notable sex differences were also found, particularly in Europe where males showed higher rates of Type I alignment and females higher rates of Type III in both healthy and osteoarthritic populations.

These findings suggest that knee alignment phenotypes are influenced by multiple factors including geography, osteoarthritis presence, and biological sex, indicating the need for population-specific approaches to knee replacement surgery and potentially musculoskeletal rehabilitation strategies. The results support developing personalized treatment approaches that account for these demographic and pathological variations in knee alignment patterns.

COMPARABLE JOINT AWARENESS AND IMPLANT SURVIVAL AT MIDTERM FOLLOW-UP BETWEEN CR AND PS TKA: AN ANATOMIC PHENOTYPE-BASED PROPENSITY SCORE-MATCHED ANALYSIS.

This study aimed to compare joint awareness and implant survival between cruciate-retaining (CR) and posterior-stabilized (PS) total knee arthroplasty implants while accounting for patients' preoperative anatomical differences. The researchers analyzed 728 patients who received either CR or PS implants, using propensity score matching to control for demographics and anatomical parameters including coronal plane alignment of the knee (CPAK) phenotypes, then assessed outcomes over a minimum 6.5-year follow-up.

The main findings showed no significant differences in joint awareness scores or implant survival rates between CR and PS implants when anatomical factors were properly matched. However, important anatomical phenotype-based differences emerged: patients with valgus CPAK types (III and VI) had the lowest survival rates regardless of implant type, with CR implants performing particularly poorly in these valgus phenotypes, while high valgus lateral distal femoral angles specifically increased revision risk for PS implants.

These findings suggest that preoperative anatomical phenotyping, particularly identifying valgus alignment patterns, should guide implant selection and patient counseling, as certain anatomical configurations may predispose to higher revision rates regardless of implant design choice.

TARGETING OSTEOSARCOPENIA AND MULTIMORBIDITY FOR FRAILTY PREVENTION THROUGH IDENTIFICATION AND DEEP PHENOTYPING METHODS IN HEALTHY AGEING AND HIGH-BURDEN DISEASE COHORTS (OPTIMA-C): A LONGITUDINAL OBSERVATIONAL COHORT STUDY PROTOCOL FOR NEUROMUSCULOSKELETAL MUSCLE HEALTH.

**Study Summary:**

The OPTIMA-C study aims to identify and track different patterns of muscle and bone health deterioration (osteosarcopenia) across multiple conditions to prevent frailty in patients with stroke, traumatic brain injury, knee osteoarthritis, and breast cancer. This 3-year longitudinal study will use comprehensive assessments including muscle ultrasound, body composition analysis, physical performance tests, blood biomarkers, and patient-reported outcomes to monitor participants from acute illness through chronic recovery phases. The research seeks to identify distinct phenotypes or subgroups of patients based on their patterns of muscle loss, bone health, inflammation, and functional decline over time. These findings could enable clinicians and physiotherapists to develop more targeted, personalized rehabilitation strategies and early intervention programs to prevent frailty and optimize recovery outcomes for different patient subgroups.

A NOVEL HARRIS HAWKS OPTIMIZATION-BASED CLUSTERING METHOD FOR ELUCIDATING GENETIC ASSOCIATIONS IN OSTEOARTHRITIS AND DIVERSE CANCER TYPES.

This study aimed to investigate genetic associations between osteoarthritis (particularly knee and hip OA) and various cancer types (bladder, kidney, breast, and prostate) using a novel machine learning approach. The researchers developed and applied a new clustering method called Harris Hawks Optimization-based Clustering (HHO-C) to analyze genetic datasets, marking the first use of machine learning to explore genetic connections between OA and these specific cancers. The study created a comprehensive genetic dataset and demonstrated the effectiveness of the HHO-C method for handling complex genetic data, though specific findings about identified genetic subgroups or phenotypes are not detailed in the abstract. The research potentially opens new avenues for understanding shared genetic mechanisms between OA and cancer, which could inform future diagnostic approaches and treatment strategies, though direct implications for current physiotherapy or rehabilitation practices are not immediately apparent from this genetic-focused investigation.

CLINICAL OUTCOME OF COMBINED TYPES 1, 2, AND 3 LATERAL HINGE FRACTURES AFTER OPEN-WEDGE HIGH TIBIAL OSTEOTOMY: A CASE REPORT.

This case report describes the management of rare combined lateral hinge fractures (types 1, 2, and 3) following open-wedge high tibial osteotomy in a 48-year-old woman with medial knee osteoarthritis. The patient had pre-existing bone atrophy from previous cancer treatment, and multiple risk factors contributed to the complex fracture pattern including large correction angle (13°), bone quality issues, and technical surgical factors. Conservative management using weight-bearing restriction combined with low-intensity pulsed ultrasound (LIPUS) successfully achieved bone healing without significant loss of correction or nonunion. At 16-month follow-up, the patient achieved pain-free walking, demonstrating that combined conservative approaches can effectively manage complex post-surgical complications in high-risk patients, potentially avoiding revision surgery and supporting successful rehabilitation outcomes.

PHENOTYPIC SCREENING IDENTIFIED POLYDATIN ALLEVIATING CARTILAGE DEGENERATION BY MODULATING SIRT3-DEPENDENT MITOCHONDRIAL DYSFUNCTION.

This study aimed to identify anti-inflammatory polyphenols as potential therapeutic alternatives for osteoarthritis treatment using high-content screening of a polyphenol library. The researchers used an IL-1β-stimulated inflammatory cell model to screen 16 polyphenolic compounds, then tested the most promising candidate (polydatin) in two mouse OA models (DMM and MIA) with radiological, histological, and mitochondrial function assessments.

The screening identified six active compounds that inhibited cartilage degradation marker MMP-13, with polydatin showing the strongest dose-dependent anti-inflammatory effects by suppressing MMP-13 and protecting type II collagen. In vivo testing revealed that polydatin treatment reduced osteophyte formation, alleviated cartilage breakdown, and improved OA scores through activation of the SIRT3/SOD2 pathway, which enhanced mitochondrial function and reduced oxidative stress.

While this study doesn't specifically identify OA phenotypes or subgroups, it suggests that patients with OA characterized by high inflammatory activity and mitochondrial dysfunction might particularly benefit from polyphenol-based interventions. For clinical management, these findings support investigating polydatin as a potential adjunct therapy, though translation to physiotherapy practice would require further research on optimal delivery methods and patient selection criteria.

POSTERIOR TIBIAL SLOPE IS INDEPENDENT OF CORONAL PLANE KNEE ALIGNMENT AND NEEDS TO BE ASSESSED TO DETERMINE KNEE PHENOTYPE.

This study aimed to investigate whether posterior tibial slope (PTS), a key sagittal plane measurement, correlates with the coronal plane alignment of the knee (CPAK) classification system used in personalized total knee arthroplasty. The researchers analyzed radiographs from 420 patients (747 legs) of Japanese, Chinese, and Indian ethnicity, measuring both coronal alignment using CPAK and sagittal alignment via PTS. The key finding was that PTS and CPAK showed weak or no correlation, indicating that coronal and sagittal knee alignments are largely independent of each other, with significant ethnic variations observed (Indian patients had the steepest PTS, Japanese the flattest). These results suggest that comprehensive knee phenotyping for personalized TKA requires assessment of both coronal and sagittal planes rather than relying solely on coronal alignment, and that ethnic background should be considered when planning individualized treatment approaches.

FAMILIAL RISKS OF FIVE TYPES OF OSTEOARTHRITIS IN FIRST-, SECOND- AND THIRD-DEGREE RELATIVES - A NATIONWIDE SWEDISH FAMILY STUDY.

This nationwide Swedish family study investigated the hereditary patterns of five osteoarthritis (OA) types across different degrees of family relationships, analyzing data from over 6.5 million individuals linked through national registries between 1997-2018. The researchers calculated familial hazard ratios for poly-, hip-, knee-, thumb-, and other-OA among twins, full-siblings, half-siblings, and cousins, adjusting for demographic and health factors.

The study revealed that all five OA types showed significant familial clustering that correlated with genetic relatedness, with thumb OA demonstrating the strongest hereditary component (HR 2.60 in full-siblings), followed by poly-OA (HR 2.29) and hip OA (HR 2.04), while knee OA showed the weakest familial risk (HR 1.75). These findings suggest distinct phenotypic subgroups of OA with varying genetic contributions, indicating that different joint sites may have different underlying pathophysiological mechanisms.

For clinical practice, these results highlight the importance of family history in OA risk assessment and suggest that preventive strategies and early interventions may be particularly valuable for individuals with strong family histories, especially for thumb and hip OA where genetic factors appear most influential.

CORRECTION: EXOSOMES OF HUMAN FETAL CARTILAGE PROGENITOR CELLS (HFCPCS) INHIBITED INTERLEUKIN-1Β (IL-1Β)-INDUCED OSTEOARTHRITIS PHENOTYPE VIA MIR-125B-5P IN VITRO.

I cannot provide a meaningful summary of this study because the abstract is not available (marked as "NA").

While the title suggests this is a correction to a study investigating exosomes from human fetal cartilage progenitor cells and their potential anti-inflammatory effects in osteoarthritis through microRNA mechanisms, I would need the actual abstract content to accurately summarize:

1. The specific study objectives and experimental design
2. The key methodological approaches used
3. The main findings regarding osteoarthritis phenotypes or cellular responses
4. The clinical implications for osteoarthritis management or rehabilitation strategies

To provide you with a proper summary, please provide the complete abstract text.

GENETIC MARKERS FOR KNEE OSTEOARTHRITIS PRESENCE ARE NOT ASSOCIATED WITH DISEASE PROGRESSION - DATA FROM THE IMI-APPROACH COHORT.

This study investigated whether genetic markers previously linked to knee osteoarthritis (OA) presence could predict disease progression over 24 months in 297 patients from the IMI-APPROACH cohort. The researchers analyzed 30 known single nucleotide polymorphisms (SNPs) using progression measures including joint space narrowing, pain changes, and radiographic worsening, while also conducting genome-wide association analysis and creating polygenic risk scores.

The key finding was that genetic markers associated with having knee OA were not predictive of how the disease progresses - neither individual SNPs nor combined polygenic risk scores showed significant associations with OA progression. However, the genome-wide analysis identified 19 different genetic variants specifically associated with joint space narrowing, located near genes like PLCL2, CDYL2, and NTNG1.

These results suggest that knee OA presence and progression may represent distinct biological processes with different genetic underpinnings, indicating that patients cannot be stratified for progression risk based on current genetic markers for OA susceptibility. For clinicians and physiotherapists, this implies that genetic testing for known OA risk variants would not currently help identify patients at higher risk of rapid progression who might benefit from more intensive monitoring or early intervention strategies.

SYNOVIAL FLUID EXTRACELLULAR VESICLES FROM PATIENTS WITH SEVERE OSTEOARTHRITIS DIFFERENTIALLY PROMOTE A PRO-CATABOLIC, INFLAMMATORY CHONDROCYTE PHENOTYPE.

This study investigated how extracellular vesicles (EVs) in synovial fluid from osteoarthritis patients with different disease severities affect cartilage cells (chondrocytes). Researchers collected synovial fluid from knee surgery patients, stratified them into mild/moderate and severe OA groups using clinical scores, then isolated EVs and tested their effects on chondrocytes using advanced molecular analysis techniques.

The key finding was that patients with severe OA had more abundant, smaller synovial fluid EVs that promoted harmful chondrocyte responses compared to those from mild/moderate OA patients. When exposed to severe OA EVs, chondrocytes showed increased inflammatory gene expression, greater production of cartilage-degrading enzymes (MMPs), and elevated pain-related molecules (nerve growth factor and substance P).

These results suggest that synovial fluid EVs may represent distinct OA phenotypes based on disease severity, with severe OA characterized by more destructive intercellular communication. For clinical management, this research highlights the potential for targeting EVs as a therapeutic approach and suggests that patients with severe OA may require more aggressive anti-inflammatory treatments to break the cycle of cartilage destruction and pain sensitization.

DECIPHERING THE ANTI-SENESCENT EFFECTS OF CLIOQUINOL: LIFESPAN PROLONGATION, METABOLIC HOMEOSTASIS, AND PHENOTYPIC REHABILITATION IN DROSOPHILA MELANOGASTER.

This study investigated clioquinol's (CQ) potential anti-aging effects using Drosophila melanogaster fruit flies as a model system, given emerging evidence of CQ's therapeutic benefits in osteoarthritis and neurodegenerative diseases. Researchers tested CQ supplementation in normal flies, high-fat diet flies, and Alzheimer's disease model flies, measuring lifespan, stress resistance, metabolism, motility, and conducting transcriptomic analysis to identify underlying molecular mechanisms. Key findings showed that CQ extended lifespan across all fly groups, improved motor function and stress resistance, enhanced metabolic health, and activated multiple beneficial cellular pathways including anti-inflammatory and longevity-promoting signaling cascades. While this pre-clinical research suggests CQ may have therapeutic potential for age-related musculoskeletal conditions like osteoarthritis, the findings require validation in human studies before clinical applications can be considered, and the drug's previous neurotoxicity concerns would need careful evaluation in any future therapeutic development.

EMERGING CONCEPTS AND CHALLENGES IN THE DEVELOPMENT OF DISEASE-MODIFYING OSTEOARTHRITIS DRUGS - A MORE REFINED PERSPECTIVE.

This review examined why disease-modifying osteoarthritis drugs (DMOADs) have consistently failed in clinical trials despite promising preclinical results. The authors analyzed various therapeutic approaches including antioxidants, anti-inflammatory drugs, and growth factors, while evaluating limitations in animal models and clinical trial design. Key findings highlighted that poor patient stratification into distinct disease endotypes and phenotypes, along with inadequate clinical outcome measures, contribute significantly to trial failures. The implications suggest that future osteoarthritis management and research should focus on better phenotyping patients into subgroups before treatment selection, potentially leading to more personalized therapeutic approaches in both drug development and physiotherapy interventions.

FEMORAL COMPONENT ROTATIONAL ALIGNMENT IN ROBOTIC-ASSISTED TOTAL KNEE ARTHROPLASTY WITH FUNCTIONAL KNEE POSITIONING VARIES ACROSS KNEE PHENOTYPES WITHOUT AFFECTING CLINICAL OUTCOMES.

This study investigated how femoral component rotational alignment varies across different knee phenotypes in robotic-assisted total knee arthroplasty using functional positioning, and whether these variations affect patient outcomes. The researchers analyzed 219 patients who underwent robotic TKA, using preoperative CT scans to classify knee phenotypes according to the CPAK (Coronal Plane Alignment of the Knee) system and measuring intraoperative femoral component rotation, with clinical outcomes assessed at minimum 2-year follow-up using validated questionnaires.

The study found that femoral component rotational alignment varied significantly among different knee phenotypes, ranging from 6.9° internal rotation to 6.6° external rotation relative to the surgical transepicondylar axis. Despite these substantial variations in component positioning, there were no significant associations between femoral component rotation and patient-reported outcomes, and no patellofemoral complications were reported.

These findings suggest that personalized, phenotype-specific implant positioning in robotic TKA may be safe and effective, challenging traditional "one-size-fits-all" alignment approaches and supporting individualized surgical strategies that adapt to patient-specific anatomy without compromising clinical outcomes or rehabilitation success.

RETHINKING ARTHRITIS: EXPLORING ITS TYPES AND EMERGING MANAGEMENT STRATEGIES.

This comprehensive review aimed to examine the various types of arthritis and evaluate emerging management strategies beyond traditional approaches. The authors conducted a literature review covering the pathophysiology and clinical features of major arthritis types (osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, and juvenile idiopathic arthritis) plus 39 less common variants. The key finding emphasizes that arthritis represents a highly heterogeneous group of disorders requiring individualized treatment approaches, as traditional pharmacological and non-pharmacological interventions have shown limited success in halting disease progression. For clinical management, the review highlights promising emerging strategies including nanotechnology-based drug delivery, dietary modifications, stem cell therapy, gene therapy, telemedicine, and artificial intelligence, suggesting that physiotherapists and clinicians should adopt personalized, multi-faceted treatment approaches that address the cellular and molecular diversity of different arthritis phenotypes.

SEMAPHORIN4B IS ELEVATED IN RHEUMATOID ARTHRITIS AND ENHANCES THE INFLAMMATORY PHENOTYPE OF MACROPHAGES AND FIBROBLAST-LIKE SYNOVIOCYTES.

This study investigated the role of Semaphorin4B (SEMA4B) in rheumatoid arthritis (RA) by analyzing its expression and functional effects on immune and synovial cells. Researchers used cell culture experiments with macrophages and fibroblast-like synoviocytes from RA and osteoarthritis patients, along with 3D tissue models, to examine how SEMA4B influences inflammation and cell behavior.

The key finding was that SEMA4B expression is elevated in RA synovial tissue compared to osteoarthritis, and SEMA4B promotes an aggressive inflammatory phenotype in both macrophages and synovial fibroblasts. When stimulated with SEMA4B, these cells showed increased migration, invasion, and production of inflammatory molecules (IL-6, IL-8, TNF-α) and tissue-degrading enzymes (MMP-1, MMP-3).

These results suggest SEMA4B contributes to the destructive joint processes characteristic of RA, potentially representing a new therapeutic target for managing inflammatory joint disease and its associated tissue damage.

THE ASSOCIATION BETWEEN THE AMERICAN HEART ASSOCIATION'S NEW "LIFE'S ESSENTIAL 8" AND DIFFERENT TYPES OF ARTHRITIS: INSIGHTS FROM A LARGE POPULATION STUDY.

This large population study examined the relationship between cardiovascular health, measured using the American Heart Association's new "Life's Essential 8" (LE8) score, and different types of arthritis in 29,324 US adults from NHANES data (2005-2018). The researchers used weighted logistic regression, subgroup analysis, and restricted cubic spline analysis to assess associations between LE8 scores (grouped into tertiles) and osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis.

The study found a strong inverse linear relationship between cardiovascular health and arthritis prevalence, with higher LE8 scores associated with significantly lower rates of OA (10.14% to 4.61% across tertiles) and RA (9.60% to 2.86%), though no significant association was found for psoriatic arthritis. Specific cardiovascular health factors including diet, exercise, smoking status, BMI, and blood pressure were particularly associated with OA risk.

These findings suggest that arthritis phenotyping should consider cardiovascular health status as a key characteristic, potentially identifying subgroups of patients who may benefit from integrated cardiovascular and musculoskeletal interventions. For physiotherapy practice, this supports adopting holistic approaches that address cardiovascular risk factors alongside traditional joint-focused treatments, particularly emphasizing lifestyle modifications around diet,

PREOPERATIVE CPAK PHENOTYPE DOES NOT AFFECT CLINICAL AND RADIOLOGICAL OUTCOMES AFTER MEDIAL CLOSING-WEDGE DISTAL FEMORAL OSTEOTOMY IN VALGUS KNEES AT 8-YEAR FOLLOW-UP.

This study aimed to evaluate whether different preoperative coronal plane alignment of the knee (CPAK) phenotypes influence long-term outcomes following medial closing-wedge distal femoral osteotomy in patients with valgus knee deformity. The researchers conducted a retrospective analysis of 51 patients (54 knees) who underwent this corrective surgery, using radiographic measurements to classify knee alignment phenotypes and validated clinical outcome scores (IKDC, KOOS, Tegner, VAS) at an average 8-year follow-up.

The study found that all patients showed significant clinical improvements and successful radiological correction regardless of their initial CPAK phenotype, with no significant differences in outcomes between the most common preoperative phenotypes (CPAK 3 and 6) or postoperative phenotypes (CPAK 5 and 8). These findings suggest that preoperative knee alignment phenotype does not need to influence surgical decision-making or predict outcomes for this procedure, indicating that medial closing-wedge distal femoral osteotomy is consistently effective across different valgus alignment patterns. For clinicians, this supports a standardized approach to surgical correction without requiring phenotype-specific modifications to treatment protocols or rehabilitation strategies.

THE UTILITY OF ANIMAL MODELS IN UNDERSTANDING OSTEOARTHRITIS (OA) PATHOGENESIS - AN UPDATE ON THE IMPACT OF GENETICALLY MODIFIED MICE.

This review examined how genetically modified mouse models have advanced understanding of osteoarthritis (OA) pathogenesis and phenotyping over seven decades of research. The authors traced four key methodological milestones, from early studies showing mice share human OA risk factors (age, sex, diet, genetics) through the development of spontaneous genetic mutations, reproducible inducible models, and modern genetically modified approaches that have identified over 500 genes affecting OA development.

The research revealed critical evidence for distinct OA phenotypes and endotypes, with approximately 35% of molecular targets showing different effects between post-traumatic OA versus spontaneous/age-related OA, supporting the concept of OA as multiple diseases rather than a single condition.

For clinical management and physiotherapy, these findings highlight the importance of patient stratification based on OA subtype (traumatic versus age-related onset) when developing treatment approaches, as different molecular pathways may require tailored interventions rather than one-size-fits-all therapies.

AMELOGENIN NULL MICE DEVELOP OSTEOARTHRITIS, WHILE ITS APPLICATION MITIGATES DISEASE PHENOTYPES IN A RAT MODEL.

This study investigated whether amelogenin, a protein that promotes cartilage and bone healing, plays a protective role in osteoarthritis development and progression. The researchers compared aged mice lacking amelogenin to normal mice using imaging and tissue analysis, and tested amelogenin treatment in rats with surgically-induced knee osteoarthritis.

Mice without amelogenin developed severe osteoarthritis features (cartilage loss, joint narrowing, bone spurs) by 23 months, while normal mice showed only mild age-related changes, indicating amelogenin deficiency creates a more severe osteoarthritis phenotype. In the rat model, a single amelogenin treatment significantly slowed disease progression, improved cartilage quality, and recruited stem cells to damaged areas compared to untreated controls.

These findings suggest amelogenin could serve as a disease-modifying treatment for osteoarthritis, potentially offering physiotherapists and clinicians a new therapeutic option that addresses underlying joint deterioration rather than just symptoms.

KEY INSIGHTS AND IMPLICATIONS OF CARTILAGE DEGRADATION IN OSTEOARTHRITIS.

This review aimed to synthesize current understanding of cartilage degradation mechanisms in osteoarthritis and their implications for treatment development. The authors conducted a narrative review examining the molecular pathways involved in cartilage breakdown, including chondrocyte dysfunction, inflammatory feedback loops, and interactions between joint tissues (cartilage, synovium, and subchondral bone).

The review highlights that osteoarthritis exhibits significant heterogeneity with various recognized phenotypes and endotypes, though consensus on subtype classification remains lacking. Key findings emphasize that OA is a complex whole-joint disease involving inflammatory processes rather than simple mechanical wear-and-tear.

For clinical management, the authors note that timely treatment of joint injuries and meniscus repair represent the best current strategies to prevent post-traumatic OA, while emerging approaches like regenerative medicine show promise. The development of disease-modifying drugs is hampered by slow disease progression, highlighting the need for better biomarkers for early diagnosis and patient stratification to advance personalized treatment approaches.

POSTEROMEDIAL VARUS FATIGUE FRAGMENT (PVFF) IN SEVERE VARUS KNEE OSTEOARTHRITIS PHENOTYPE: INCIDENCE, SURGICAL IMPLICATIONS, AND MANAGEMENT.

This study aimed to investigate the incidence and surgical significance of posteromedial varus fatigue fragments (PVFF) - chronic stress fractures that develop in the tibial plateau of patients with severe varus knee osteoarthritis. The researchers conducted a retrospective analysis of 856 consecutive total knee arthroplasty cases, examining preoperative radiographs and intraoperative findings to identify PVFF occurrence and its impact on surgical procedures.

The study identified PVFF in 17 patients (1.99%), with only half of these cases visible on preoperative imaging, indicating this condition is frequently missed during standard radiographic assessment. All PVFF cases occurred exclusively in patients with severe varus deformity (>15°) and complete ACL deficiency, suggesting this represents a distinct phenotype within the broader severe varus osteoarthritis population.

The presence of PVFF significantly complicated surgical management, as removal of these fragments during surgery altered knee stability and gap balancing, often requiring modifications to implant selection including tibial stems or augments. These findings highlight the importance of recognizing this specific osteoarthritis phenotype preoperatively, as it requires specialized surgical planning and techniques to optimize outcomes in total knee arthroplasty.

BIOMATERIAL STRATEGIES IN OSTEOARTHRITIS: NEW INSIGHTS BRIDGING AGING PHENOTYPES AND HYPOXIC MICROENVIRONMENT PATHOLOGY.

This review aimed to examine how advancing knowledge of osteoarthritis (OA) pathophysiology, particularly aging and hypoxic microenvironments, can inform biomaterial scaffold development for treatment. The authors conducted a comprehensive literature review focusing on aging-related phenotypes (characterized by impaired autophagy and inflammation) and novel NDRG-mediated hypoxia regulation mechanisms that operate independently of traditional hypoxia-inducible factors. Key findings identified distinct OA phenotypes linked to aging processes across different joint tissues, along with alternative hypoxic pathways that contribute to disease progression. The review highlights promising biomaterial strategies including hydrogels, nanoparticles, microneedles, and exosomes that could enhance drug delivery, reduce side effects, and target the adverse joint microenvironment—suggesting potential for developing more personalized, phenotype-specific interventions that could complement physiotherapy approaches in OA management.

THICK OR THIN? IMPLICATIONS OF CARTILAGE ARCHITECTURE FOR OSTEOARTHRITIS RISK IN SEDENTARY LIFESTYLES.

This narrative review examined how cartilage thickness variations may influence osteoarthritis (OA) risk in sedentary populations, challenging traditional assumptions about cartilage structure and protection. The authors synthesized current literature on mechanical loading and metabolic regulation, focusing on nutrient transport mechanisms in cartilage during prolonged immobilization.

The key finding suggests a paradoxical phenotype where thicker cartilage—despite superior load-bearing capacity—may be more vulnerable to OA during sedentary behavior due to impaired nutrient diffusion and waste clearance, leading to metabolic dysfunction in deeper cartilage layers. This identifies a potential subgroup of individuals with thicker cartilage who may be at higher risk for OA development when engaging in prolonged sedentary activities.

The implications for physiotherapy and management emphasize the importance of regular joint mobilization and movement interventions, particularly for sedentary populations, suggesting that prevention strategies should focus on maintaining cartilage metabolic health through periodic mechanical stimulation rather than solely protecting joints from loading.

ULTRASOUND PHENOTYPE-BASED APPROACH TO TREATMENT CHOICE IN OSTEOARTHRITIS.

This study aimed to evaluate how musculoskeletal ultrasound (MSK US) can identify different osteoarthritis (OA) phenotypes to guide treatment selection, addressing the current lack of effective tools for patient stratification in OA management. The researchers conducted a single-center prospective study of 259 consecutive OA patients from September 2023 to June 2024, using ultrasound to identify predominant phenotypes based on the most damaged tissue structures (bone, cartilage, synovium, etc.) across different joint locations.

The study revealed distinct ultrasound phenotype patterns by joint location: knee OA was predominantly characterized by intra-articular effusion (37.9%), while hip and hand OA were mainly associated with altered subchondral bone changes (47.1% and 55.4% respectively), and shoulder OA primarily showed extra-articular soft tissue changes (46.2%). These findings suggest that MSK US can effectively identify joint-specific pathological patterns in OA, providing a rationale for selecting targeted treatments based on the underlying pathogenetic mechanism and affected tissue structures, which could improve therapeutic outcomes and patient stratification in clinical practice.

FURTHER EVIDENCE THAT CHONDROCALCINOSIS 1 (CCAL1) IS A CONFIRMED MENDELIAN PHENOTYPE WITH A KNOWN MOLECULAR BASIS.

This study aimed to characterize a rare genetic form of chondrocalcinosis (CCAL1) by analyzing a German family with calcium pyrophosphate dihydrate deposition disease and confirming its molecular basis. The researchers conducted clinical phenotyping of 12 family members across multiple generations and performed genetic analysis to identify disease-causing variants in the TNFRSF11B gene.

The study identified that all affected individuals carried the same recurrent genetic variant that extends the osteoprotegerin protein, with the condition manifesting in the third decade of life as severe spinal problems and variable disability levels. Notably, the researchers expanded the known phenotype of CCAL1 to potentially include short stature (median height at 10th percentile), along with previously recognized features like demineralization, osteoporosis, and progressive height loss.

These findings confirm CCAL1 as a distinct rare genetic disorder with early-onset presentation, which has important implications for physiotherapy management as patients may require specialized spine-focused interventions from a young age, along with monitoring for osteoporotic changes and fracture prevention strategies.

EXPLORATION OF BIOACTIVE VARIANTS OF THE BMP7-DERIVED P[63-82] PEPTIDE FOR AMELIORATING THE OA-ASSOCIATED CHONDROCYTE PHENOTYPE.

This study aimed to optimize a bone morphogenetic protein 7-derived peptide (P[63-82]) as a potential disease-modifying treatment for osteoarthritis by testing 33 different peptide modifications. The researchers used chondrocytes and synovial fluid from end-stage OA patients undergoing knee replacement surgery to evaluate the peptides' effects on cartilage-related gene expression, protein levels, and other biomarkers of the OA phenotype.

Among all tested modifications, only one cyclized variant (C2) showed similar or superior bioactivity compared to the original linear peptide, effectively reducing the inflammatory and hypertrophic characteristics of OA chondrocytes - particularly decreasing harmful matrix metalloproteinase-13 levels and increasing beneficial collagen type 2 expression. The C2 variant demonstrated enhanced potency at lower concentrations and maintained effectiveness even in the presence of inflammatory conditions that typically worsen the OA phenotype.

These findings suggest that while peptide-based therapies may offer promise for treating the underlying cartilage degradation in OA, structural modifications must be carefully evaluated as most alterations compromise biological activity, highlighting the need for cautious optimization in developing new therapeutic approaches for musculoskeletal conditions.

REGULATORY ROLES OF 13 TYPES OF RNA MODIFICATIONS IN OSTEOARTHRITIS: BASED ON BULK AND SINGLE-CELL RNA ANALYSIS.

This study investigated how 13 different RNA modification patterns contribute to osteoarthritis (OA) development and progression using advanced computational analysis of gene expression data from both tissue samples and individual cells. The researchers used machine learning methods (random forest and support vector machines) along with single-cell RNA sequencing to identify key genes involved in RNA modifications and characterized distinct chondrocyte (cartilage cell) populations and their communication patterns.

The analysis revealed two distinct OA phenotypes: Subtype 1 showed high inflammatory activity driven by LSM1 gene expression (associated with m7G RNA modification), while genes related to m6A RNA modifications (YTHDC1, METTL3, IGF2BP2) appeared to have anti-inflammatory effects. At the cellular level, the study identified specific chondrocyte subpopulations with different roles - regulatory chondrocytes (REGC) showed decreased m6A modifications, while effector chondrocytes (EC) had high LSM1 expression and communicated with other cell types through inflammatory pathways.

These findings suggest that RNA modifications play crucial regulatory roles in OA and could serve as biomarkers for identifying inflammatory versus anti-inflammatory disease subtypes. For clinical management, this research points toward potential personalized treatment approaches where patients with high LSM1/inflammatory phenotypes might benefit from anti-inflammatory interventions, while those with m6

ADVANCES IN MOLECULAR IMAGING FOR OSTEOARTHRITIS.

This review examines the potential of advanced molecular imaging, particularly positron emission tomography (PET), to improve early detection and monitoring of osteoarthritis by identifying distinct disease phenotypes. The authors analyzed current PET imaging capabilities using tracers like [¹⁸F]-FDG and [¹⁸F]-NAF, as well as emerging radiotracers targeting specific cell populations (TSPO for immune cells, FAPI for mesenchymal cells) that can detect metabolic, inflammatory, and cellular changes before structural damage appears on conventional imaging. Key findings suggest that while current PET tracers can assess synovial inflammation and bone remodeling, newer cell-specific tracers show promise for characterizing inflammatory endotypes in OA, potentially enabling identification of patient subgroups based on underlying pathophysiological processes rather than just structural changes. These advances could revolutionize OA management by enabling earlier intervention strategies and precision medicine approaches tailored to specific inflammatory phenotypes, though further validation studies and longitudinal research are needed before clinical implementation.

SEX DIFFERENCES IN FRAILTY IN MILAN OVER THE LAST 2000 YEARS: A HAZARDS-BASED AND CUMULATIVE PHENOTYPE APPROACH.

This bioarchaeological study aimed to examine sex differences in frailty across 2000 years of Milan's history using skeletal remains from 492 adults across five historical periods (Roman to contemporary). The researchers applied a hazards-based approach to develop a 4-biomarker frailty index incorporating cribra orbitalia, cribra femoralis/humeralis, porotic hyperostosis, and notably the *absence* of osteoarthritis as mortality risk factors. Key findings revealed that frailty peaked during the Late Middle Ages and was lowest in contemporary populations, but surprisingly showed no significant sex differences across any time period. The lack of expected lower frailty in females (who typically have biological advantages) suggests cultural factors may have negatively impacted female health outcomes, providing important insights for understanding how social determinants can override biological protective factors in musculoskeletal health patterns.

DIAGNOSING, TREATING AND MONITORING THE INFLAMMATORY ENDOTYPE IN OSTEOARTHRITIS CLINICAL TRIALS.

This perspective article examines how to identify and target an inflammatory endotype (subgroup) of osteoarthritis patients in clinical trials. The authors reviewed recent evidence from clinical studies, biomarker datasets, and imaging studies to outline tools for identifying patients with significant inflammatory features, including elevated cytokine levels (IL-1, TNF-α), imaging-confirmed synovitis, and specific biomarker signatures. Key findings suggest that patients with this inflammatory endotype may respond more favorably to anti-inflammatory treatments, offering both symptomatic relief and structural benefits. However, standardized tools for identifying these patients are still lacking and not widely adopted in clinical practice, highlighting the need for better phenotyping methods to improve clinical trial design and enable more targeted, personalized treatment approaches for osteoarthritis management.

POLY-ETHER-ETHER-KETONE WEAR PARTICLES INDUCE A PRO-INFLAMMATORY PHENOTYPE IN A HUMAN MONOCYTIC CELL LINE.

This study investigated whether poly-ether-ether-ketone (PEEK) wear particles from joint implants trigger inflammatory responses in immune cells. Researchers exposed human macrophage cells to PEEK particles generated from wear simulation and measured inflammatory markers, gene expression, and cellular pathways over 24 hours using various laboratory techniques.

The findings revealed that PEEK particles induced a distinct pro-inflammatory phenotype in macrophages, significantly increasing production of inflammatory proteins and genes (IL-8, CCL2, CCL3, CCL4) at higher doses, along with reactive oxygen species production and inflammasome activation. Importantly, this inflammatory response occurred through a pathway independent of the typical Toll-like receptor 4 mechanism, suggesting PEEK particles trigger inflammation through alternative cellular mechanisms.

These results have important implications for patients with PEEK-containing joint implants, as the pro-inflammatory response could potentially contribute to implant-related complications or tissue reactions, highlighting the need for monitoring inflammatory phenotypes in patients with these devices during rehabilitation and long-term management.

MULTIDIMENSIONAL CHARACTERIZATION AND CLINICAL PROFILING OF SUBCHONDRAL BONE ENDOTYPES IN HIP OSTEOARTHRITIS.

This study aimed to identify distinct subgroups (endotypes) of hip osteoarthritis patients based on subchondral bone characteristics to inform personalized treatment approaches. Researchers analyzed femoral heads from 38 patients undergoing hip replacement surgery using advanced bone analysis techniques and statistical clustering methods to classify patients based on bone properties.

The analysis revealed three distinct endotypes: (1) low bone mass with low turnover, (2) intermediate bone mass with high turnover, and (3) high bone mass with high turnover (characterized by abundant osteocytes). These endotypes showed different bone microstructure, cellular activity, and bone marrow fat characteristics, with high turnover groups displaying increased signs of fat breakdown.

These findings suggest that hip osteoarthritis patients could benefit from endotype-specific treatments targeting bone turnover, bone cells, or bone marrow fat rather than the current one-size-fits-all approach, potentially leading to disease-modifying therapies that address underlying bone pathology rather than just managing symptoms.

PAIN PHENOTYPE IN KNEE OSTEOARTHRITIS: IMPLICATIONS FOR MECHANISM-BASED THERAPY.

This narrative review aimed to classify knee osteoarthritis pain into distinct phenotypes based on the International Association for the Study of Pain framework and propose targeted treatment strategies for each type. The authors categorized pain into three main types: nociceptive pain (further subdivided into inflammatory, mechanical, and bone marrow lesion-related pain), neuropathic pain, and nociplastic pain, with each phenotype having distinct underlying mechanisms and clinical presentations.

The review identified five pain phenotypes with specific management recommendations: inflammatory pain responds to anti-inflammatory medications; mechanical pain benefits from weight loss, biomechanical interventions, and rehabilitation training; bone marrow lesion-related pain may improve with reduced weight-bearing and anti-osteoporosis treatments; neuropathic pain requires antidepressants or anticonvulsants; and nociplastic pain should be managed primarily through non-pharmacological approaches using a biopsychosocial model.

For physiotherapy practice, this phenotyping approach suggests that mechanical pain patients would be ideal candidates for exercise therapy and biomechanical interventions, while those with nociplastic pain would benefit more from comprehensive lifestyle modification programs, sleep hygiene education, and psychologically-informed physiotherapy approaches. The authors emphasize that clinicians must identify the predominant pain phenotype in each patient to develop personalized treatment plans, as many patients present with mixed pain types.

SUBSTRATE STIFFNESS MODULATES HYPERTROPHIC CHONDROCYTE REVERSION AND CHONDROGENIC PHENOTYPE RESTORATION.

This study investigated whether the mechanical stiffness of the tissue environment can reverse the harmful transformation of cartilage cells (hypertrophic chondrocytes) that occurs in osteoarthritis back to their healthy, cartilage-producing state. Researchers cultured these transformed cells on artificial substrates with varying stiffness levels (78-508 kPa) and analyzed changes in cell behavior, gene expression, and signaling pathways over 7-21 days. The key finding was that softer substrates (78 kPa) successfully reversed the cells back to a healthy chondrogenic phenotype with increased cartilage-specific markers, while stiffer substrates promoted further harmful transformation toward bone-like cells through YAP-mediated mechanotransduction pathways. These results suggest that controlling the mechanical environment through softer biomaterials or potentially through physiotherapy interventions that modify tissue mechanics could offer new therapeutic strategies for cartilage regeneration and osteoarthritis treatment.

PREOPERATIVE PATIENT-REPORTED OUTCOME MEASURES PHENOTYPES AS PREDICTORS OF 1-YEAR OUTCOMES IN MEDIAL UNICOMPARTMENTAL KNEE ARTHROPLASTY: INSIGHTS FROM 940 UKA PROCEDURES.

This study aimed to determine whether preoperative patient-reported outcome measure (PROM) phenotypes based on pain, function, and mental health could predict 1-year outcomes following medial unicompartmental knee arthroplasty (UKA). The researchers analyzed 941 patients who underwent UKA between 2016-2022, creating eight distinct phenotypes by categorizing patients as above or below median scores for knee pain, physical function, and mental health measures.

The key finding was that certain preoperative phenotypes were associated with different outcome trajectories - some phenotypes had lower likelihood of failing to achieve meaningful clinical improvements, while paradoxically being more likely to fail reaching acceptable symptom thresholds across all knee function domains at one year.

These phenotypes could help clinicians optimize surgical timing and identify high-risk patients who may benefit from targeted preoperative interventions, such as prehabilitation programs or enhanced expectation management, despite still experiencing meaningful improvements after surgery.

DISTINCT 3-DIMENSIONAL MORPHOLOGIES OF ARTHRITIC KNEE ANATOMY EXIST: CT-BASED PHENOTYPING OFFERS OUTLIER DETECTION IN TOTAL KNEE ARTHROPLASTY.

This study aimed to develop a comprehensive 3D classification system for arthritic knee anatomy using CT scans to improve preoperative planning and evaluation of total knee arthroplasty (TKA). Researchers analyzed 1,352 pre-TKA CT scans using deep learning technology to extract 27 lower-extremity measurements, then applied unsupervised machine learning clustering to identify distinct anatomical patterns across all three planes (coronal, axial, and sagittal).

The analysis revealed four distinct morphological phenotypes among arthritic knees, with Types 1 and 3 representing clear anatomical outliers that together comprise 26% of knees undergoing TKA. Key distinguishing features between phenotypes included hip rotation, tibial slope, hip-knee-ankle alignment, and various angular measurements of the tibia and femur.

This 3D phenotyping approach offers significant implications for personalized TKA management by identifying anatomical outliers that may require specialized surgical techniques, implant selection, or rehabilitation protocols, potentially improving patient outcomes and reducing post-surgical dissatisfaction in this morphologically diverse population.

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This study aimed to identify shared molecular mechanisms underlying cartilage degradation across different types of arthritis, particularly focusing on the role of the WAC protein and its regulator H2BK120UB1. The researchers used human cartilage samples from RA and OA patients, experimental mouse models of arthritis, cartilage-specific gene knockout techniques, and molecular docking simulations to investigate these pathways.

The key finding revealed that WAC acts as a central regulator of cartilage degradation in both rheumatoid arthritis and osteoarthritis by controlling inflammatory mediator secretion through epigenetic mechanisms (H2BK120UB1 and H3K27ME3 pathways). Importantly, the study identified that despite their different underlying pathologies, RA and OA share this common molecular pathway for cartilage destruction, suggesting they may represent phenotypic variations of a broader arthritic process rather than entirely distinct conditions.

The research demonstrates that doxercalciferol (a vitamin D analog) can effectively inhibit WAC and reduce cartilage degradation in experimental models, offering a potential therapeutic target that could benefit patients across different arthritis phenotypes. This finding suggests that treatments targeting WAC could provide a unified approach to managing cartilage destruction in various forms of arthritis, potentially informing more personalized rehabilitation strategies based on this shared molecular mechanism rather than traditional diagnostic

DOES HSCRP PROVIDE INSIGHTS INTO AN INFLAMMATORY PHENOTYPE OF KNEE OSTEOARTHRITIS?

This study investigated whether high-sensitivity C-reactive protein (hsCRP) could identify an inflammatory knee osteoarthritis phenotype characterized by joint inflammation visible on MRI. Researchers analyzed data from 792 participants in the MOST study, measuring hsCRP levels and scoring knee inflammation using MRI scans with the WORMS system, defining inflammation as significant synovitis or joint effusion.

The study found no association between hsCRP levels (including the ≥2mg/dL threshold used in cardiac research) and the presence or severity of knee joint inflammation on MRI, with hsCRP showing poor ability to predict which knees had inflammatory changes. These findings suggest that hsCRP is not a reliable blood marker for identifying the local inflammatory phenotype of knee osteoarthritis, despite previous promising results in cardiac patients.

For clinicians and physiotherapists, this indicates that hsCRP testing alone cannot reliably identify patients with inflammatory knee OA who might benefit from anti-inflammatory treatments, and other approaches for phenotyping inflammatory OA subgroups are needed.

OMICS-DRIVEN INSIGHTS INTO THE MOLECULAR PATHWAYS DRIVING OSTEOARTHRITIS PATHOGENESIS.

This review examined how advanced omics technologies (genomics, transcriptomics, proteomics, and metabolomics) are being used to understand osteoarthritis (OA) pathogenesis and identify distinct disease subtypes. The authors analyzed single- and multi-omics studies that investigate molecular pathways driving OA progression, with particular focus on identifying molecular subtypes (endotypes) and therapeutic subtypes (theratypes) of the disease. Key findings revealed that multi-omics integration has uncovered important interactions between inflammatory, metabolic, and tissue-degrading processes, while spatial proteomics is providing new insights into the varied cellular makeup of synovial tissue. Despite these advances in understanding OA's molecular complexity, the authors note that significant challenges remain—including data complexity, lack of standardized analysis methods, and limited clinical validation—which have prevented translation into effective disease-modifying treatments, suggesting that future personalized OA management and physiotherapy approaches will require integration of artificial intelligence and advanced omics techniques within long-term patient studies.

EVALUATION OF OUTCOMES AT MEAN 4.8 YEARS AFTER REPAIR OF TYPES 3 AND 4 LATERAL MENISCAL OBLIQUE RADIAL TEARS DURING ACL RECONSTRUCTION.

This study evaluated long-term outcomes following surgical repair of lateral meniscal oblique radial tears (LMORTs) that occurred alongside ACL injuries. The researchers conducted a retrospective review of 25 patients who underwent LMORT repair during ACL reconstruction, following 18 patients for an average of 4.8 years and assessing repair failure rates, complications, and patient-reported outcomes using validated questionnaires (KOOS, Marx activity scale, VAS pain scores).

The study found no LMORT repair failures and generally favorable patient-reported outcomes (mean KOOS score 86.5), indicating good functional recovery. However, 50% of patients experienced complications requiring additional interventions, primarily due to joint stiffness, persistent pain, or re-injury.

These findings suggest that while LMORT repair during ACL reconstruction has a low failure rate and produces good functional outcomes, clinicians should anticipate a high complication rate. This information is valuable for setting patient expectations and may indicate the need for enhanced post-operative rehabilitation protocols focusing on preventing stiffness and optimizing pain management in this patient population.

RADIOGRAPHIC RISK FACTORS FOR EXCESSIVE JOINT LINE OBLIQUITY AFTER KNEE OSTEOTOMY FOR MEDIAL OSTEOARTHRITIS: A PHENOTYPE-BASED APPROACH.

This study investigated how knee alignment patterns (phenotypes) change after high tibial osteotomy (HTO) surgery and identified risk factors for excessive joint line obliquity, which leads to poor outcomes. The researchers analyzed 348 knees using standing X-rays before surgery and one year after, classifying alignment into 9 phenotypes based on whether the knee was bent inward/outward (varus/valgus) and where the main deformity was located (apex position).

The study found that patients with a specific preoperative phenotype (Type IV - varus knee with neutral apex position) had significantly higher rates of excessive joint line obliquity after surgery (14.5% vs 0.7-10.4% in other types). Two key preoperative measurements proved highly predictive of this complication: the mechanical lateral distal femoral angle ≥90.2° and arithmetic joint line obliquity ≥-1.5°, with patients meeting these criteria having dramatically increased risk (19.8% vs 0.4% and 35.1% vs 1.4%, respectively).

These findings suggest that surgeons should carefully evaluate preoperative knee alignment phenotypes and specific angular measurements to identify high-risk patients who may need modified surgical approaches or closer postoperative monitoring to prevent complications that could compromise rehabilitation outcomes.

KNEE OSTEOARTHRITIS (OA)-RELATED PHENOTYPES OF MYELOID-DERIVED SUPPRESSOR CELLS (MDSCS) IS MEDIATED BY INFRAPATELLAR FAT PAT (IPFP)-DERIVED FACTORS IN A BODY MASS INDEX (BMI)-DEPENDENT MANNER AND POSITIVELY CORRELATES WITH IPFP-DERIVED ADIPONECTIN LEVELS.

This study investigated how obesity influences immune cell dysfunction in knee osteoarthritis by examining myeloid-derived suppressor cells (MDSCs) from the infrapatellar fat pad. Researchers isolated MDSCs from knee OA patients with varying BMI levels and performed transcriptomic analysis, while also testing how fat pad-derived factors affect MDSC behavior in laboratory cultures. The findings revealed distinct OA-related phenotypes: patients with moderate-to-high BMI showed upregulated OA-related genes and inflammatory pathways in their MDSCs, while low BMI patients had downregulated pathways; additionally, fat pad-derived factors promoted harmful MDSC characteristics including increased inflammation, reduced immune regulation, and enhanced bone destruction potential in a BMI-dependent manner. These results suggest that obesity drives knee OA progression through metabolic changes in fat tissue that create pro-inflammatory immune cell phenotypes, indicating that BMI-based stratification and targeted interventions addressing metabolic dysfunction may be important considerations in OA management and rehabilitation strategies.

PREOPERATIVE CLINICAL PHENOTYPING FOR INDIVIDUALISED REHABILITATION IN END-STAGE KNEE OSTEOARTHRITIS.

This study aimed to identify distinct clinical phenotypes in patients with end-stage knee osteoarthritis awaiting total knee replacement surgery to inform individualized preoperative management strategies. Using exploratory factor analysis on demographic data, physical examination findings, patient-reported outcomes, and functional measures from a South African population, researchers identified three distinct phenotypes: (1) "Gait and Weight" characterized by poor gait mechanics, obesity, and low self-efficacy; (2) "Central Pain" involving central sensitization, depression, and reduced function; and (3) "Functional Factors" reflecting muscle weakness and functional limitations. These findings demonstrate significant heterogeneity in end-stage knee osteoarthritis presentations and suggest that preoperative rehabilitation should be tailored accordingly. The phenotypes support implementing multidisciplinary approaches that may include weight management programs for the first group, pain science education and psychological support for the second group, and targeted strengthening exercises for the third group to optimize post-surgical outcomes.

IMPACT OF MECHANICAL AXIS POSITION AND CORONAL PLANE ALIGNMENT PHENOTYPES ON CLINICAL OUTCOMES IN MEDIAL OPENING WEDGE HIGH TIBIAL OSTEOTOMY.

This study investigated how different knee alignment patterns (phenotypes) affect clinical outcomes after medial opening wedge high tibial osteotomy (MOWHTO), a surgical procedure for knee osteoarthritis. The researchers analyzed 147 knees using the Coronal Plane Alignment of the Knee (CPAK) classification system, which categorizes patients based on mechanical axis position and joint line angle, and assessed clinical outcomes using knee function scores.

The study found that patients who transitioned from the predominant pre-operative pattern (Type I - varus with angled joint line) to Types V or VI (neutral/valgus alignment with horizontal joint line) achieved significantly better clinical outcomes. Optimal results occurred when the weight-bearing line was positioned at 50-60% across the tibial plateau, with restoration of a horizontal joint line being crucial for success.

These findings suggest that the CPAK classification system can guide individualized surgical correction strategies in MOWHTO, emphasizing that successful treatment requires both correcting the mechanical axis and restoring proper joint line orientation. For clinicians and physiotherapists, this highlights the importance of considering individual alignment phenotypes when planning treatment and setting rehabilitation goals, as different patients may require different correction targets to achieve optimal outcomes.

RESVERATROL TREATMENT INCREASES SIRTUIN 1 LEVELS AND ALLEVIATES FRAILTY PHENOTYPE IN KNEE OSTEOARTHRITIS PATIENTS: A RANDOMISED PLACEBO-CONTROLLED CLINICAL TRIAL.

This randomized controlled trial investigated whether resveratrol supplementation could improve both knee osteoarthritis symptoms and frailty in older adults, given the shared pathophysiological mechanisms between these conditions. The study randomized 123 patients aged 63-75 years with knee OA to receive either 500mg daily resveratrol or placebo for 16 weeks, measuring outcomes including pain scores (WOMAC), functional measures (Oxford Knee Score), frailty assessments, handgrip strength, and plasma SIRT1 levels.

Resveratrol treatment significantly reduced frailty severity, walking pain, and overall WOMAC scores while improving knee function (Oxford Knee Score) and handgrip strength, with these benefits associated with increased plasma SIRT1 levels. These findings suggest that targeting shared aging pathways through resveratrol supplementation may offer a novel therapeutic approach for managing the combined burden of osteoarthritis and frailty in older adults, potentially complementing traditional physiotherapy interventions focused on strength and mobility.

CLINICAL AND DGEMRIC EVALUATION OF MICROFRAGMENTED ADIPOSE TISSUE VERSUS HYALURONIC ACID IN INFLAMMATORY PHENOTYPE OF KNEE OSTEOARTHRITIS: A RANDOMIZED CONTROLLED TRIAL.

This randomized controlled trial compared microfragmented adipose tissue (MFAT) versus hyaluronic acid (HA) injections in 53 patients with early-to-moderate inflammatory knee osteoarthritis, using clinical outcomes and specialized MRI (dGEMRIC) to assess cartilage quality over six months. Both treatments significantly improved pain and function scores and cartilage glycosaminoglycan content, with MFAT showing superior improvement in knee symptoms (particularly stiffness, swelling, and grinding sensations) compared to HA, though most differences weren't statistically significant. Notably, all patients who showed structural cartilage improvement on MRI also experienced meaningful pain relief, while no patients had cartilage benefits without symptom improvement. These findings suggest MFAT may be particularly beneficial for managing inflammatory features in knee OA, while the strong correlation between cartilage changes and clinical response indicates that dGEMRIC imaging could help physiotherapists and clinicians predict which patients will respond well to these regenerative treatments.

THE INFLUENCE OF NATIVE CORONAL PLANE ALIGNMENT KNEE PHENOTYPE ON TWO-YEAR OUTCOMES OF FUNCTIONALLY ALIGNED ROBOT-ASSISTED TOTAL KNEE ARTHROPLASTY.

This study aimed to evaluate two-year outcomes of functionally aligned total knee arthroplasty (FA-TKA) and determine whether different native knee alignment patterns (CPAK phenotypes) influence clinical results. The researchers analyzed 904 robot-assisted FA-TKAs using CT scans to classify knee alignment phenotypes before and after surgery, measuring patient-reported outcomes and component positioning over two years.

The main findings showed that all patients experienced significant clinical improvements regardless of their native knee alignment phenotype, with no meaningful differences in outcomes between different alignment patterns. Notably, about one-third of patients (35.1%) changed their knee alignment phenotype after surgery, yet this change did not negatively impact their clinical outcomes compared to those who maintained their original alignment pattern.

These results suggest that functional alignment techniques can successfully improve knee function across diverse patient populations with different baseline knee alignment patterns. For clinicians, this indicates that FA-TKA may be a viable approach that doesn't require strict adherence to preserving native alignment phenotypes, potentially allowing for more individualized surgical planning while still achieving excellent patient outcomes.

TOWARDS STRATIFICATION IN OSTEOARTHRITIS: A REVIEW OF THE SCIENTIFIC TERMINOLOGY USED IN PUBLISHED BASIC RESEARCH.

This study examined how key stratification terms (phenotype, subtype, subgroup, and endotype) are used in osteoarthritis research by analyzing their frequency and chronological appearance in published literature from 2010-2024. The researchers reviewed studies involving human OA tissues and fluids, focusing on unmanipulated samples analyzed with unbiased methods while excluding reviews, clinical trials, and animal studies.

The analysis revealed that "phenotype" was the most frequently used term, followed by "subgroup" and "subtype," with "endotype" being newly introduced in 2019, and overall usage of these terms tripled over the 14-year period. Importantly, these terms were rarely defined and often used interchangeably within single papers, particularly in cartilage and serum studies, creating potential for misinterpretation across research disciplines.

The findings suggest that clearer terminology standards are needed, with the authors proposing that "phenotype" should describe clinical features while "endotype" should refer to molecular mechanisms underlying OA pathogenesis. This standardization could improve communication between researchers and clinicians, ultimately supporting more effective patient stratification and personalized rehabilitation approaches in osteoarthritis management.

BIPLANAR RADIOGRAPHIC ANALYSIS OF KNEE ALIGNMENT: A STEPWISE APPROACH FOR PHENOTYPE CLASSIFICATION AND KNEE ARTHROPLASTY PLANNING.

This review aimed to establish a standardized approach for analyzing knee alignment using biplanar radiography to improve phenotype classification and surgical planning. The authors compared two main classification systems - the simpler 2D Coronal Plane Alignment of the Knee (CPAK) system versus the more detailed 3D Functional Knee Phenotype system that includes segmental deformities and laxity parameters - while emphasizing the importance of sagittal plane measurements alongside coronal alignment. The review identified that comprehensive phenotyping requires integration of both coronal and sagittal measurements, with the functional phenotype approach offering more granular subgroup classification that accounts for individual variations in bone alignment and soft tissue behavior. For clinical management, this individualized phenotyping approach could improve total knee arthroplasty outcomes by better matching implant positioning to native knee biomechanics, though the implications for non-surgical physiotherapy interventions based on these phenotypes require further investigation.

INTEGRATIVE SPATIALLY RESOLVED PROTEOMIC AND METABOLOMIC IMAGING REVEALS SYNOVITIS ENDOTYPES IMPLICATED IN OSTEOARTHRITIS PROGRESSION.

This study aimed to identify distinct molecular patterns (endotypes) of synovial inflammation in osteoarthritis by mapping protein and metabolite distributions within knee joint tissue. The researchers used advanced imaging techniques (MALDI mass spectrometry and spatial proteomics) to analyze over 3,500 proteins and 79 metabolites from human knee samples, creating detailed molecular maps of inflamed synovial tissue.

The analysis revealed four distinct stages of osteoarthritis synovitis progression: quiescent (inactive), microvasculopathic (blood vessel damage), pre-fibrotic (early scarring), and post-fibrotic (established scarring), with evidence that blood vessel injury triggers an immune-metabolic pathway leading to tissue scarring. These findings suggest that osteoarthritis synovitis follows a predictable molecular progression from vascular damage through immune activation to tissue fibrosis.

For clinical management, this research indicates that osteoarthritis patients could potentially be stratified into different treatment groups based on their synovitis stage, with early-stage patients possibly benefiting from vascular-protective therapies and later-stage patients requiring anti-fibrotic approaches—though validation in larger patient groups is needed before clinical application.

DIFFERENTIALLY EXPRESSED SALIVARY MIRNAS IN TEMPOROMANDIBULAR DISORDERS.

This study aimed to identify salivary microRNA (miRNA) signatures that could help diagnose and understand temporomandibular disorders (TMDs), which are complex jaw conditions that are difficult to diagnose and treat effectively. Researchers collected saliva samples from 9 women with TMD and 8 healthy controls, then used advanced sequencing techniques to compare miRNA expression patterns between the groups. The analysis revealed 187 significantly different miRNAs in TMD patients (125 increased, 62 decreased), with several linked to processes affecting cell adhesion, nerve function, and inflammation—some of which overlap with miRNAs found in rheumatoid arthritis and osteoarthritis. While the study didn't identify distinct TMD subgroups, five specific miRNAs showed strong correlations with pain intensity levels, suggesting that salivary miRNA profiling could become a non-invasive diagnostic tool for TMDs and potentially guide more personalized treatment approaches for physiotherapists and clinicians managing these challenging conditions.

UNRESTRICTED KINEMATIC ALIGNMENT IN VARUS TOTAL KNEE ARTHROPLASTY OUTPERFORMS MECHANICAL ALIGNMENT IN CPAK I PHENOTYPE, BUT YIELDS COMPARABLE OUTCOMES IN CPAK IV: A RETROSPECTIVE ANALYSIS FROM THE FP-UCBM KNEE STUDY GROUP.

This study compared two surgical alignment techniques in knee replacement surgery for patients with varus (inward-angled) osteoarthritis, examining whether patient-specific bone shape phenotypes influence outcomes. Researchers analyzed 349 total knee arthroplasty cases, comparing mechanical alignment (MA) versus unrestricted kinematic alignment (KA), and categorized patients using the CPAK classification system based on joint line angles.

The study found that kinematic alignment generally produced superior clinical outcomes compared to mechanical alignment, with significantly better knee function and patient satisfaction scores at one-year follow-up. However, when patients were grouped by CPAK phenotype, kinematic alignment only showed clear advantages in CPAK I patients (those with more neutral joint line angles), while both techniques performed equally well in CPAK IV patients (those with more oblique joint lines).

These findings suggest that patient phenotyping using bone shape characteristics can help surgeons select the most appropriate alignment technique for individual patients. For physiotherapists and clinicians, this indicates that post-surgical rehabilitation expectations and approaches may need to be tailored based on both the patient's original bone anatomy phenotype and the surgical technique used, as different combinations yield varying functional outcomes.

TARGETING THE SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE TO MODIFY OSTEOARTHRITIS IN AGING.

This review study aimed to examine how cellular aging (senescence) in cartilage cells contributes to osteoarthritis development and to evaluate potential treatments targeting this aging process. The authors consolidated existing research on the molecular mechanisms driving cartilage cell aging and critically assessed various therapeutic strategies, including senolytic drugs (like dasatinib + quercetin), senomorphic compounds (such as rapamycin and metformin), antioxidant treatments, and stem cell-based therapies.

The key finding identifies the senescence-associated secretory phenotype (SASP) as a distinct osteoarthritis subgroup, where aging cartilage cells continuously release inflammatory substances (IL1β, IL6, TNFα) and cartilage-degrading enzymes (MMP3, MMP13) that drive joint destruction. The review highlights that this aging-related phenotype involves specific molecular pathways including NFκB/MAPK signaling, oxidative stress, and mitochondrial dysfunction.

For clinical management, this research suggests that osteoarthritis patients, particularly older adults, might benefit from targeted anti-aging therapies rather than traditional anti-inflammatory approaches alone, potentially offering new directions for both prevention and treatment strategies in musculoskeletal rehabilitation.

TARGETING CASPASE-1 IN OSTEOARTHRITIS: MULTI-OMICS INSIGHTS INTO THE EFFECTS OF VX-765 ON HUMAN CHONDROCYTE FUNCTION AND PHENOTYPE.

This study investigated whether targeting caspase-1 with the inhibitor VX-765 could serve as a potential treatment for osteoarthritis by examining its effects on cartilage cell function. Researchers used multiple approaches including gene expression analysis, protein studies, and cell function tests on human cartilage cells treated with inflammatory signals, comparing osteoarthritis cells to healthy controls.

The findings revealed that caspase-1 was elevated in osteoarthritis cartilage cells and associated with harmful processes like inflammation and cartilage breakdown, while VX-765 treatment successfully reduced these damaging effects and improved cell migration and metabolism. Importantly, the study identified significant variation between different patients in how their cartilage cells responded to VX-765 treatment, and genetic analysis suggested that certain genetic variants may influence osteoarthritis risk and potentially treatment response.

These results suggest that caspase-1 inhibitors like VX-765 could represent a new disease-modifying treatment approach for osteoarthritis, but the patient-to-patient variability indicates that personalized medicine approaches may be needed to optimize treatment effectiveness in clinical practice.

VARUS AND NEUTRAL CORONAL KNEE PHENOTYPES DOMINATE GLOBALLY: INSIGHTS FROM A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE CPAK CLASSIFICATION.

This systematic review and meta-analysis examined the global distribution of knee alignment patterns using the Coronal Plane Alignment of the Knee (CPAK) classification system across 33 studies involving over 32,000 knees. The researchers analyzed how these alignment phenotypes vary by osteoarthritis status, age, ethnicity, and geographic region using pooled prevalence estimates from radiographic assessments.

The study found that varus (Type 1, 31.5%) and neutral (Type 2, 26.4%) alignment patterns dominate globally, with important demographic variations: Type 1 alignment was most common in osteoarthritic knees (35.4%) and patients over 40 years, while Type 2 was more frequent in healthy knees (22.9%) and younger individuals. Geographic differences were also evident, with Asian populations showing predominantly Type 1 alignment and Caucasian populations more often displaying Type 2.

These findings support the use of personalized alignment strategies in total knee arthroplasty based on individual phenotypes, moving away from one-size-fits-all approaches. For physiotherapists and clinicians, understanding these alignment patterns may inform targeted interventions and help predict which patients might benefit from specific treatment approaches, though the classification's limitation to coronal plane measurements means additional assessment parameters remain necessary for comprehensive management planning.

POSTERIOR TIBIAL SLOPE VARIES ACROSS FUNCTIONAL TIBIAL PHENOTYPES BUT NOT CPAK CATEGORIES: A RADIOGRAPHIC ANALYSIS FROM THE FP-UCBM KNEE STUDY GROUP.

This study investigated how posterior tibial slope (the backward tilt of the shin bone) relates to different knee alignment classification systems in patients with severe osteoarthritis. Researchers analyzed pre-operative X-rays from 217 knees scheduled for total knee replacement, measuring sagittal plane alignment (posterior tibial slope) and comparing it across two classification systems: CPAK categories and functional tibial phenotypes.

The key finding was that posterior tibial slope varied significantly across functional tibial phenotypes (ranging from 5.7° to 8.2° depending on the subtype) but showed no meaningful differences between CPAK categories. This suggests that functional tibial phenotypes better capture the complexity of knee alignment by incorporating both coronal (side-to-side) and sagittal (front-to-back) plane deformities.

These results indicate that functional tibial phenotypes may be more clinically useful than CPAK categories for understanding the full three-dimensional nature of knee deformity in osteoarthritis. For surgical planning and potentially for physiotherapy approaches, considering posterior tibial slope alongside functional phenotypes could lead to more personalized treatment strategies that account for the complete alignment picture rather than just coronal plane deformity.

JOINT ACIDOSIS AND ACID-SENSING RECEPTORS AND ION CHANNELS IN OSTEOARTHRITIS PATHOBIOLOGY AND THERAPY.

This review examined joint acidosis as an underappreciated feature of osteoarthritis (OA) pathobiology, synthesizing evidence on how localized pH reductions within cartilage and other joint tissues contribute to disease progression and symptoms. The authors analyzed metabolic drivers of acidosis (including hypoxia-driven glycolysis and impaired proton transport), cellular acid-sensing mechanisms through specialized receptors and ion channels, and the downstream effects on tissue degradation and pain signaling.

Key findings suggest that acidic microenvironments create distinct pathological niches that promote cartilage breakdown through cathepsin-mediated proteolysis, suppress tissue repair, trigger chondrocyte stress responses, and directly activate pain receptors (ASIC3, TRPV1). The evidence points toward potential OA subgroups or "acidotic endotypes" that could be identified through pH-aware clinical phenotyping and targeted imaging approaches.

For clinical management, this framework suggests novel therapeutic strategies including acid-sensing receptor modulation, cathepsin inhibition, metabolic interventions to reduce lactate production, and pH-responsive drug delivery systems, potentially offering more personalized, mechanism-based treatments for patients with acidosis-driven OA phenotypes.

INTEGRATIVE PHENOTYPING OF KNEE OSTEOARTHRITIS: LINKING WOMAC CUT-OFFS, KELLGREN-LAWRENCE GRADES, AND CLUSTER ANALYSIS FOR PERSONALIZED CARE.

This study aimed to develop WOMAC score cut-offs linked to radiographic severity and identify distinct knee osteoarthritis phenotypes to support personalized care approaches. Researchers analyzed 99 adults using receiver operating characteristic (ROC) analysis to establish WOMAC cut-offs for Kellgren-Lawrence grades, and applied cluster analysis incorporating functional, radiological, demographic, and psychological factors to identify patient subgroups.

The analysis revealed a five-tier WOMAC classification system (minimal ≤24, mild 25-41, moderate 42-69, severe 70-86, extreme ≥87) and identified four distinct phenotypes: young patients with minimal symptoms, those with moderate disease and functional deficits, patients with moderate-to-severe symptoms and joint narrowing, and a severely affected group with high pain, disability, advanced structural damage, psychological distress, and elevated BMI. These findings suggest that combining functional assessments with radiographic grading and demographic factors can identify meaningful patient subgroups, supporting the development of targeted treatment strategies rather than one-size-fits-all approaches in knee osteoarthritis management and physiotherapy practice.

A GUIDE TO THE TYPES, STRUCTURES, AND MULTIFACETED FUNCTIONS OF MATRIX METALLOPROTEINASES IN CANCER.

I notice there's a mismatch between your request and the provided abstract. You've asked me to focus on osteoarthritis phenotyping and musculoskeletal rehabilitation, but the abstract is primarily about matrix metalloproteinases (MMPs) in cancer research.

Based on the actual content provided, here's a summary:

This review aimed to comprehensively examine the structural types and multifaceted functions of matrix metalloproteinases (MMPs) across physiological and pathological conditions, with particular emphasis on cancer progression. The authors conducted a comprehensive literature review analyzing MMP structural domains, substrate specificity, and biological functions in normal tissue remodeling and disease states including osteoarthritis, fibrosis, and cancer. The key finding is that MMPs demonstrate complex, context-dependent roles that can be either protective or harmful depending on tumor stage, anatomic location, and specific enzyme characteristics, which explains why early MMP inhibitor trials failed. For musculoskeletal conditions, this suggests that MMP-targeted therapies for osteoarthritis will require precise phenotyping to identify which patients have predominantly destructive versus protective MMP activity patterns, potentially informing personalized rehabilitation strategies that either support or counteract specific MMP functions.

MICROBIAL METABOLITE TIGLOSIDE ALLEVIATES OSTEOARTHRITIS BY REPOLARIZING MACROPHAGES FROM M1 TO M2 PHENOTYPE THROUGH TRAFD1 DESTABILIZATION AND TRAFD1-MEDIATED NF-ΚB/STAT6 SIGNALING PATHWAYS.

This study investigated whether tigloside (TIG), a microbial metabolite, could treat osteoarthritis by modifying inflammatory processes in joint tissues. The researchers used laboratory experiments with macrophages (immune cells) from both animal models and human OA patients to examine how TIG affects inflammation and cartilage damage. The key finding was that TIG shifts macrophages from a harmful pro-inflammatory state (M1 phenotype) to a beneficial anti-inflammatory state (M2 phenotype) by targeting specific cellular signaling pathways, ultimately reducing joint inflammation, pain, and cartilage deterioration. These results suggest TIG could represent a new disease-modifying treatment for OA that addresses root causes rather than just symptoms, potentially offering physiotherapists and clinicians a therapeutic option that promotes tissue healing alongside rehabilitation interventions.

PRECISION OBESITY MEDICINE: A PHENOTYPE-GUIDED FRAMEWORK FOR PHARMACOLOGIC THERAPY ACROSS THE LIFESPAN.

This study aimed to develop a precision medicine framework for obesity pharmacotherapy by organizing treatment approaches according to patient phenotypes, complications, age, and behavioral traits. The authors conducted a narrative review synthesizing evidence from randomized trials, meta-analyses, and real-world data through May 2025, examining how newer anti-obesity medications (GLP-1 receptor agonists, dual GIP/GLP-1 agonists) perform across different patient subgroups and life stages. Key findings showed that these medications provide benefits beyond weight loss for specific phenotypes: semaglutide reduces cardiovascular events in established heart disease, both agents improve heart failure symptoms and kidney function regardless of weight loss achieved, and they effectively treat mechanical complications like osteoarthritis through weight reduction. For musculoskeletal rehabilitation, this phenotype-based approach suggests that anti-obesity medications can complement physiotherapy for osteoarthritis management, while the finding that liraglutide preserves lean mass when combined with resistance training indicates potential for integrated pharmaceutical-exercise interventions, particularly in older adults at risk of sarcopenia.

INTEROBSERVER RELIABILITY OF CORONAL PLANE ALIGNMENT OF THE KNEE (CPAK) PHENOTYPE CLASSIFICATION : EXTERNAL VALIDATION USING DATA FROM THE OSTEOARTHRITIS INITIATIVE.

This study evaluated the reliability of the Coronal Plane Alignment of the Knee (CPAK) classification system, which categorizes patients into nine phenotypes based on knee alignment measurements to guide personalized total knee arthroplasty decisions. Two readers measured knee alignment angles on X-rays from 1,128 patients in the Osteoarthritis Initiative database, with Monte Carlo simulations used to assess how measurement errors affect phenotype classification accuracy.

Despite excellent reliability in individual angle measurements (errors of only 0.41-0.71 degrees), the researchers found a concerning 20% disagreement rate between readers when classifying patients into CPAK phenotypes. The study revealed that even tiny measurement differences can lead to patients being placed in different phenotype categories, with near-perfect measurement precision required to achieve acceptable classification reliability.

These findings suggest that CPAK phenotyping using standard long-leg X-rays may have significant limitations for clinical decision-making in knee replacement surgery, and CT imaging might be necessary to improve classification accuracy, particularly for patients whose measurements fall near the boundaries between phenotype categories.

A PHENOTYPE-DRIVEN DATA AND DRUG REPURPOSING STRATEGY USED TO IDENTIFY POTENTIAL TREATMENTS TARGETING CHONDROCYTE HYPERTROPHY IN OSTEOARTHRITIS.

This study aimed to identify existing drugs that could reverse the harmful hypertrophic phenotype of cartilage cells (chondrocytes) in osteoarthritis using a novel drug repurposing approach. The researchers analyzed single-cell gene expression data from osteoarthritic cartilage to identify drugs that might reverse the disease signature, then tested promising candidates in human cartilage samples in the laboratory. They identified cobimetinib (a MEK1/2 inhibitor) as effectively reducing harmful genes associated with cartilage breakdown (MMP13, ADAMTS5) while promoting protective cartilage genes (collagen type 2, aggrecan), with single-cell analysis confirming that cells shifted toward a healthier state. This proof-of-concept study demonstrates how combining large-scale genetic data with drug repurposing strategies could accelerate the discovery of treatments targeting specific cellular changes in osteoarthritis, potentially offering new therapeutic options for a condition that currently lacks effective pharmacological treatments.

CAUSAL EFFECTS OF STIMULUS-INDUCED BLOOD CELL PHENOTYPES ON THE RISK OF PRIMARY KNEE OSTEOARTHRITIS: A TWO-SAMPLE MENDELIAN RANDOMIZATION STUDY.

This study aimed to investigate whether specific immune-related blood cell responses causally influence the risk of developing primary knee osteoarthritis (PKOA). The researchers used Mendelian randomization, a genetic analysis method, to examine data from over 1,300 European blood donors and compared it with PKOA data from nearly 463,000 individuals in the Finnish population.

The analysis identified four key blood cell phenotypes that significantly affect PKOA risk: red blood cell stability when exposed to cellular stress, neutrophil changes in response to bacterial components, baseline variations in certain immune cells, and structural changes in white blood cells during immune activation. These findings suggest that individual differences in how blood cells respond to immune challenges may predispose some people to developing knee osteoarthritis.

For clinical practice, these immune-related blood cell patterns could potentially serve as early biomarkers to identify patients at higher risk for PKOA before joint symptoms appear. This could enable physiotherapists and clinicians to implement preventive strategies, such as targeted exercise programs or lifestyle interventions, earlier in the disease process when joint preservation may be more effective.

THE LOAD STUDY: THE ASSOCIATION BETWEEN DIFFERENT TYPES OF PHYSICAL ACTIVITY AND THE PROGRESSION OF KNEE OSTEOARTHRITIS-A COHORT STUDY PROTOCOL.

**Study Summary:**

The LOAD Study is a prospective cohort study designed to examine how different types of physical activity (hiking, running, cycling, and tennis) and their intensities affect knee osteoarthritis progression over 24 months in physically active adults aged 45-65 with early knee OA. The study will follow 300 participants (75 per activity group) using comprehensive assessments including MRI imaging, physical examinations, biomarker analysis, and continuous GPS tracking of activities, with outcomes measured through structural changes (MRI osteoarthritis knee score) and clinical symptoms (pain and function scores). By comparing four distinct activity phenotypes, this research addresses current gaps in understanding how specific exercise types influence OA progression, moving beyond previous retrospective studies that lacked comparative analysis across activity types and intensities. The findings will provide evidence-based guidance for clinicians and physiotherapists on optimal activity recommendations for people with early knee OA, potentially informing personalized exercise prescription strategies based on activity-specific risk-benefit profiles.

PREVALENCE OF NEUROPATHIC-LIKE PAIN PHENOTYPE IN PEOPLE WITH HAND OSTEOARTHRITIS: A SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS.

This systematic review and meta-analysis aimed to determine how common neuropathic-like pain is in people with hand osteoarthritis and compare characteristics between those with and without this pain type. The researchers analyzed eight studies involving 1,084 hand osteoarthritis patients, using statistical methods to pool prevalence data and compare patient characteristics between groups.

The study found that 42% of hand osteoarthritis patients experience neuropathic-like pain, and these patients were younger but reported significantly higher pain intensity (average 59mm versus 49mm on pain scales) compared to those without neuropathic-like pain. Importantly, there were no differences in sex, body weight, inflammation markers, or disease severity between the two groups, suggesting that neuropathic-like pain represents a distinct pain phenotype rather than simply reflecting more advanced disease.

These findings suggest that clinicians should routinely assess for neuropathic pain features in hand osteoarthritis patients, as this phenotype may require different pain management approaches, potentially including neuropathic pain medications alongside standard osteoarthritis treatments.

SENESCENT BONE MARROW MESENCHYMAL STEM CELLS EXACERBATE SUBCHONDRAL BONE SCLEROSIS AND OSTEOARTHRITIS VIA THE SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE.

This study investigated how aging bone marrow stem cells contribute to osteoarthritis progression by promoting harmful bone changes beneath the cartilage. Researchers used mouse models of osteoarthritis and laboratory experiments to examine senescent (aged) bone marrow mesenchymal stem cells (BMSCs) and their effects on bone formation, including analysis of secreted inflammatory factors and testing of senolytic drugs that eliminate aged cells.

The key finding revealed a distinct pathological phenotype where senescent BMSCs accumulate in the subchondral bone during osteoarthritis and release inflammatory substances (SASP) that overstimulate bone formation, leading to bone sclerosis through specific molecular pathways (MAPK8 and MAPK14). Treatment with senolytic drugs (dasatinib and quercetin) successfully cleared these harmful aged cells, reduced excessive bone formation, and slowed osteoarthritis progression in mice.

These findings suggest that targeting senescent stem cells represents a promising new therapeutic approach for osteoarthritis management, potentially offering clinicians and physiotherapists a novel treatment strategy that addresses underlying disease mechanisms rather than just symptoms.

PAIN PHENOTYPES IN KNEE OSTEOARTHRITIS: BETWEEN MECHANISTIC TAXONOMY AND CLINICAL COMPLEXITY.

I notice that the abstract is marked as "NA" (not available), which means I cannot provide a comprehensive summary of this study's methods, findings, and implications as requested.

However, based on the title alone, this appears to be a study examining pain phenotypes (distinct pain patterns or characteristics) in knee osteoarthritis patients, with a focus on bridging mechanistic understanding and clinical application.

To provide the detailed 3-4 sentence summary you've requested covering the study objective, methods, findings about phenotypes/subgroups, and clinical implications for physiotherapy management, I would need access to the actual abstract content.

Could you please provide the complete abstract, or let me know if you'd like me to help with a different paper that has an available abstract?

COMBINING MACHINE-LEARNING ASSESSMENT OF MULTIPLE MRI PATHOLOGIES AND CLINICAL PHENOTYPES FOR PREDICTING JOINT REPLACEMENT IN KNEE OSTEOARTHRITIS: DATA FROM THE OSTEOARTHRITIS INITIATIVE.

This study aimed to use machine learning to analyze multiple MRI-detected knee pathologies across different osteoarthritis phenotypes and predict knee replacement risk. The researchers applied machine learning algorithms to analyze baseline MRIs from 8,667 participants in the Osteoarthritis Initiative, assessing various joint structures (menisci, ligaments, cartilage) within three pre-defined clinical phenotypes: post-traumatic, metabolic, and age-defined clusters.

The analysis revealed distinct pathological patterns across phenotypes, with the metabolic cluster showing more cartilage lesions and the post-traumatic cluster having greater meniscal damage. Random forest models achieved excellent prediction accuracy (area under curve 0.837), identifying meniscal position, severe joint effusion, medial cartilage lesions, and metabolic phenotype as the strongest predictors of knee replacement, distinguishing high-risk patients (10% knee replacement rate at 5 years) from low-risk patients (3% rate).

These findings emphasize that comprehensive knee assessment should extend beyond cartilage damage to include meniscal pathology and inflammatory markers, providing clinicians and physiotherapists with better tools for patient stratification and targeted management strategies based on individual risk profiles and phenotypic characteristics.

[DIFFERENTIATION OF OSTEOARTHRITIS PHENOTYPES ON MRI USING ARTIFICIAL INTELLIGENCE].

This review examined how artificial intelligence (AI) can be used to identify and classify different osteoarthritis (OA) phenotypes on MRI imaging, moving beyond the traditional view of OA as a single degenerative condition. The authors conducted a selective literature review to analyze current AI approaches for OA phenotyping and their clinical applications. Key findings revealed that AI shows promise for automated cartilage damage assessment and predicting the need for joint replacement surgery, but requires close collaboration between orthopedic specialists, radiologists, and AI experts for successful clinical implementation. The study suggests that AI-based phenotyping could lead to more precise diagnoses and individualized treatment approaches, potentially improving therapeutic decision-making and patient outcomes in musculoskeletal rehabilitation.

A MULTIDIMENSIONAL DEFINITION OF PRE-OSTEOARTHRITIS: TOWARD 21ST-CENTURY SUBCLINICAL DETECTION AND TARGETED INTERVENTION.

This study proposes a framework for identifying and treating pre-osteoarthritis (pre-OA), a preclinical stage where molecular and biomechanical changes occur before symptoms or joint damage appear on X-rays. The authors used cross-disciplinary evidence from molecular profiling, advanced imaging, biomechanics, and longitudinal studies to develop a "pheno-endotype" classification system that matches early detection methods with specific underlying disease mechanisms. Key findings showed that pre-OA is characterized by early cartilage changes, inflammatory markers, and altered joint mechanics that can be detected before traditional diagnosis, creating distinct subgroups based on different biological pathways. This framework could enable personalized early interventions including lifestyle modifications, metabolic treatments, and targeted therapies, potentially transforming OA from an inevitable age-related condition into a preventable disease—though standardized diagnostic criteria and validation studies are still needed for clinical implementation.

A BOUNDED FUNCTIONAL ALIGNMENT APPROACH FOR TOTAL KNEE ARTHROPLASTY: IMPACT ON KNEE PHENOTYPE AND PATIENT-REPORTED OUTCOMES.

This study examined whether a functional alignment (FA) approach during robotic total knee arthroplasty preserves patients' natural knee alignment patterns (phenotypes) and whether maintaining these phenotypes affects patient outcomes. The researchers retrospectively analyzed 188 patients who underwent robotic TKA using a "bounded" FA technique that aimed to minimize soft tissue releases while surgeons remained unaware of patients' pre-surgical knee phenotypes, then assessed whether knees retained their original CPAK (Coronal Plane Alignment of the Knee) classification patterns.

The FA approach successfully preserved the native knee phenotype in nearly three-quarters (74.5%) of cases, with particularly high retention rates for Class I (100%) and Class III (89%) knee types. However, patients whose knee phenotypes were retained showed no significant differences in pain, function, or quality of life scores at one year compared to those whose phenotypes changed, with both groups achieving similar rates of clinically meaningful improvement.

These findings suggest that while functional alignment techniques can effectively maintain natural knee alignment patterns, precise phenotype restoration may be less critical for short-term patient outcomes than achieving proper soft tissue balance, potentially giving surgeons more flexibility in their surgical approach to optimize knee function.

ASSOCIATION OF RESIDENTIAL GREEN SPACE, BLUE SPACE, AND NATURAL ENVIRONMENT WITH OSTEOARTHRITIS RISK: THE ROLE OF AIR POLLUTION AND PHENOTYPIC AGE ACCELERATION.

This large-scale study investigated how residential natural environments (green spaces, water bodies, and natural land) affect osteoarthritis risk using data from 343,732 UK Biobank participants followed for over 12 years. Researchers measured environmental exposures within 300m and 1000m of participants' homes and used Cox regression models to assess OA risk, along with joint and mediation analyses to examine the roles of air pollution and biological aging (PhenoAge acceleration).

The study found that greater exposure to natural environments was protective against OA, with each 5% increase in green space, blue space, and natural environment associated with 4%, 5%, and 2% lower OA risk respectively, potentially preventing 9-10% of OA cases. Importantly, the researchers identified a distinct phenotypic subgroup based on biological age acceleration—individuals with younger PhenoAge experienced stronger protective benefits from natural environments, suggesting that biological aging status modifies environmental health effects.

These findings suggest that residential environment assessment could be incorporated into OA risk stratification, with particular attention to patients' biological aging profiles. For physiotherapy practice, this research supports the therapeutic value of nature-based interventions and outdoor exercise programs, especially for patients with better biological aging profiles, while highlighting the need to consider both environmental and individual aging factors in developing personalized OA management strategies.

METABOLIC-BMI PHENOTYPES AS NUTRITIONAL RISK INDICATORS FOR OSTEOARTHRITIS: EVIDENCE FROM A PROSPECTIVE COHORT OF UK ADULTS.

This study examined how metabolic health status combined with BMI affects osteoarthritis (OA) risk in middle-aged and older UK adults, using data from the English Longitudinal Study of Ageing (ELSA) to classify participants into four metabolic-BMI phenotypes. Over 10 years of follow-up with 673 new OA cases, researchers used Cox regression models to assess OA risk across different phenotype groups. The key finding was that metabolically healthy obese individuals had 54% higher OA risk and metabolically unhealthy obese individuals had 90% higher risk compared to metabolically healthy normal-weight people, while metabolically unhealthy normal-weight individuals showed no increased risk. These results suggest that combining metabolic health markers with BMI could better identify patients at high OA risk than BMI alone, potentially allowing physiotherapists and clinicians to prioritize metabolic interventions alongside weight management in obese patients for OA prevention.

SYNOVIAL FIBROBLAST RESPONSES TO DIFFERENT TYPES OF INJURY RESULTING IN CARTILAGE REPAIR OR OSTEOARTHRITIS.

This study aimed to compare how synovial fibroblasts respond to different types of joint injuries that lead to either cartilage repair or osteoarthritis development. The researchers used single-cell RNA sequencing to analyze published data from mouse models of joint surface injury (which promotes repair) and two post-traumatic osteoarthritis models (meniscus destabilization and ACL rupture) at various time points.

The analysis revealed distinct fibroblast response patterns: joint surface injury primarily triggered expansion of repair-promoting lining progenitor cells and fibroblast-like synoviocytes, while osteoarthritis-inducing injuries caused expansion of "perturbed-state fibroblasts" including myofibroblasts that drive tissue remodeling and matrix changes. All injury types activated fibroblasts with multilineage potential (capable of becoming cartilage, bone, or tendon cells), but the specific molecular pathways and timing differed between repair versus osteoarthritis outcomes.

These findings suggest that different injury mechanisms activate distinct synovial fibroblast phenotypes, which could help identify therapeutic targets for promoting joint repair while preventing osteoarthritis progression in clinical rehabilitation settings.

CORRIGENDUM TO 'ASSOCIATION OF RESIDENTIAL GREEN SPACE, BLUE SPACE, AND NATURAL ENVIRONMENT WITH OSTEOARTHRITIS RISK: THE ROLE OF AIR POLLUTION AND PHENOTYPIC AGE ACCELERATION' [ENVIRON. RES. VOLUME 292 (2025) / 123632].

I cannot provide a meaningful summary of this research as the title indicates this is a corrigendum (correction) to a previously published article, and no abstract is provided.

A corrigendum typically contains corrections to errors in the original publication rather than presenting new research findings. To write an appropriate summary focusing on osteoarthritis phenotyping and rehabilitation implications, I would need access to either:
- The abstract and content of the correction itself, or
- The abstract of the original article being corrected

If you can provide the abstract from the original study or details about what corrections were made, I'd be happy to help create the clinical summary you're looking for.

CORRIGENDUM TO "A PHENOTYPE-DRIVEN DATA AND DRUG REPURPOSING STRATEGY USED TO IDENTIFY POTENTIAL TREATMENTS TARGETING CHONDROCYTE HYPERTROPHY IN OSTEOARTHRITIS" [BIOMED. PHARMACOTHER. 193 (DECEMBER) (2025) 118773].

I'm unable to provide a summary of this research as this appears to be a corrigendum (correction notice) to a previously published article, and no abstract or content details are provided.

To write an accurate summary focusing on osteoarthritis phenotypes, study methods, findings about subgroups, and physiotherapy implications, I would need access to either:
- The abstract and key findings from the original article being corrected
- Details about what specific corrections were made
- The main content of the research study

If you could provide the abstract or key details from the original research article about chondrocyte hypertrophy phenotypes in osteoarthritis, I would be happy to create the clinical summary you've requested.

ROBOTIC-ASSISTED RESTRICTED KINEMATIC ALIGNMENT IN TOTAL KNEE ARTHROPLASTY: A MULTICENTER RETROSPECTIVE ASSESSMENT OF CORONAL PHENOTYPES AND EARLY POSTOPERATIVE OUTCOMES.

This multicenter retrospective study aimed to evaluate how different knee alignment phenotypes (classified using the CPAK system) respond to robotic-assisted total knee arthroplasty using a restricted kinematic alignment approach. The researchers analyzed 200 patients across five centers, examining pre- and post-operative alignment patterns and measuring functional outcomes at 6 months using KOOS and Forgotten Joint Score assessments.

The study found that most patients (71.5%) had Type I (predominantly varus) alignment before surgery, with this pattern being consistent across age and gender groups. The robotic-assisted restricted kinematic alignment protocol successfully achieved target corrections within the planned limits for all phenotypes, with 63.5% of Type I patients maintaining their constitutional alignment pattern post-operatively.

All patients showed significant functional improvements at 6 months, with substantial gains in both KOOS and Forgotten Joint Score measures, and no early revision surgeries were required. These findings suggest that phenotype-based surgical planning using robotic assistance can effectively restore individualized knee alignment while delivering good early outcomes, though the researchers appropriately note that without a comparison group, the improvements cannot be attributed specifically to the robotic technology or alignment strategy used.

SENESCENT SYNOVIAL INTIMAL FIBROBLASTS AGGRAVATE OSTEOARTHRITIS BY REGULATING MACROPHAGE POLARIZATION AND CHONDROCYTE PHENOTYPE THROUGH ANGPTL4-Α5Β1 AXIS.

This study aimed to investigate how senescent (aged) synovial cells contribute to osteoarthritis progression and affect communication between different joint tissues. The researchers used advanced molecular techniques including single-cell RNA sequencing and immunofluorescence to identify senescent cell populations in synovial tissue, followed by laboratory experiments to test their functional effects on macrophages and cartilage cells.

The key finding was that synovial intimal fibroblasts (SIF) showed the most pronounced premature aging compared to other synovial cells, with a specific senescent subgroup being identified. These senescent SIF cells worsen osteoarthritis by secreting a protein called ANGPTL4, which promotes inflammatory M1 macrophage activation and contributes to cartilage breakdown.

These results suggest that targeting senescent synovial cells or the ANGPTL4 pathway could represent new therapeutic approaches for osteoarthritis management, potentially complementing current physiotherapy strategies by addressing the underlying cellular mechanisms driving joint inflammation and cartilage degradation.

TRANSCRIPTOMICS IN THE STUDY OF BONE AND CARTILAGE.

This review examines recent advances in transcriptomics research (RNA sequencing technologies) applied to bone and cartilage studies in osteoarthritis and osteoporosis over the past two years. The authors analyzed bulk RNA sequencing, single-cell sequencing, and emerging spatial sequencing methods to understand cellular and molecular disease patterns. Key findings show that these advanced technologies have successfully identified distinct disease endotypes (biologically-defined subgroups) and revealed new molecular mechanisms underlying osteoarthritis and osteoporosis progression. These discoveries of cellular and molecular patterns could lead to more targeted therapeutic approaches and personalized treatment strategies, though the clinical translation of these findings into specific physiotherapy or rehabilitation protocols requires further research.

DIFFERENTIAL EXPRESSION OF BONE METABOLISM BIOMARKERS IN VARIOUS TYPES OF ARTHRITIS AND THEIR DIAGNOSTIC PERFORMANCE: A CROSS-SECTIONAL STUDY.

This cross-sectional study aimed to evaluate bone metabolism markers as diagnostic tools for differentiating between various arthritis types, including rheumatoid arthritis, systemic osteoarthritis, gouty arthritis, and ankylosing spondylitis. The researchers analyzed blood samples from 919 arthritis patients and 919 healthy controls, measuring bone formation markers (N-MID, TOTAL-P1NP, osteocalcin, bone-specific alkaline phosphatase) and bone resorption markers (β-CrossLaps, CTX-I) alongside inflammatory markers.

The study identified distinct bone metabolism patterns across arthritis types: arthritis patients showed reduced bone formation and increased bone resorption compared to controls, with specific markers performing best for different conditions—osteocalcin for systemic osteoarthritis (diagnostic accuracy 94.8%) and ankylosing spondylitis, while bone-specific alkaline phosphatase was most accurate for rheumatoid arthritis and gouty arthritis. These findings suggest that bone metabolism markers could help clinicians phenotype arthritis patients more precisely, potentially enabling more targeted treatment approaches and better monitoring of bone health in different arthritis subtypes, which is particularly relevant for physiotherapists managing loading and exercise interventions.

CYTOKINE PROFILING OF MOLECULAR ENDOTYPES OF KNEE OSTEOARTHRITIS: INSIGHTS FROM THE IMI-APPROACH COHORT.

I apologize, but I cannot provide a summary of this research paper because the abstract is listed as "NA" (not available).

To write an accurate and meaningful summary focusing on the study objective, methods, findings about osteoarthritis phenotypes/subgroups, and clinical implications, I would need access to the actual abstract content that describes:

- The study's aims and design
- The cytokine profiling methods used
- The characteristics of the IMI-APPROACH cohort
- The molecular endotypes identified
- The key findings and their clinical relevance

If you could provide the complete abstract, I would be happy to create a concise 3-4 sentence summary suitable for clinicians and researchers working in osteoarthritis phenotyping and musculoskeletal rehabilitation.

CPAK PHENOTYPES IN MEDIAL OPEN WEDGE HIGH TIBIAL OSTEOTOMY: UNDERCORRECTION AS THE KEY FACTOR INFLUENCING CLINICAL OUTCOMES AND CARTILAGE REGENERATION.

This retrospective study examined how different knee alignment patterns (CPAK phenotypes) affect outcomes following medial opening wedge high tibial osteotomy (MOWHTO) in 186 patients with knee osteoarthritis. The researchers analyzed pre- and post-operative knee alignment phenotypes and assessed outcomes using knee function scores (KOOS) and direct visualization of cartilage healing through arthroscopy in 103 patients.

The key finding was that undercorrection of the knee alignment during surgery was the primary factor determining both functional outcomes and cartilage regeneration, while the specific CPAK phenotype (knee alignment pattern) had minimal impact on results. Among patients who underwent follow-up arthroscopy, 55% showed cartilage improvement, and the mean functional scores were moderate at an average 40-month follow-up.

These results suggest that achieving adequate surgical correction is more important than the patient's specific knee alignment pattern when planning MOWHTO, indicating that this procedure can be successful across different phenotypes as long as proper correction is achieved. For clinicians, this emphasizes the critical importance of surgical precision in correction angle rather than excluding patients based on their particular alignment phenotype.

CORONAL PLANE ALIGNMENT OF THE KNEE PHENOTYPES AND ANKLE JOINT CORONAL PLANE ALIGNMENT PATTERNS IN EGYPTIAN POPULATION.

This study aimed to determine the distribution of coronal plane alignment of the knee (CPAK) phenotypes in an Egyptian population with knee osteoarthritis and examine how ankle joint alignment patterns relate to different knee alignment types. The researchers conducted a cross-sectional analysis of 527 patients (1054 knees) using radiographic measurements to classify knee alignment into 9 CPAK types and further subdivided these into 27 subtypes based on ankle joint orientation patterns.

The key findings revealed that most patients (76.4%) had varus (inward-angled) knee alignment, with CPAK types I, IV, and II being most common, and 70.2% of ankles also showed varus orientation. When combining knee and ankle alignment patterns, the most frequent subtypes were I-A, IV-A, and I-N, with a significant positive correlation found between ankle and knee alignment angles.

These population-specific phenotypes have important implications for personalized total knee arthroplasty planning in North African patients, as surgeons can now consider both knee and ankle alignment patterns when determining optimal implant positioning and surgical strategies for this demographic.

TIBIAL SLOPE VARIATION ACROSS CORONAL PLANE ALIGNMENT OF THE KNEE PHENOTYPES: A THREE-DIMENSIONAL COMPUTED TOMOGRAPHY-BASED ANALYSIS OF OSTEOARTHRITIC KNEES.

This study examined whether the CPAK (Coronal Plane Alignment of the Knee) classification system, which identifies nine knee phenotypes based on limb alignment and joint line obliquity, could predict tibial slope measurements in osteoarthritic knees. The researchers analyzed 3D CT scans from 581 knees of patients undergoing total knee replacement, using statistical analyses including multiple linear regression and ANOVA to assess correlations between CPAK phenotypes and medial tibial slope.

The findings revealed no clinically meaningful relationship between CPAK phenotypes and tibial slope, with coronal alignment factors explaining only 2.33% of tibial slope variance. While some statistically significant differences were found between specific CPAK groups (differences of 1.39-2.06 degrees), these were considered within measurement error and too small to be clinically relevant.

These results indicate that CPAK classification cannot reliably predict sagittal plane knee morphology, meaning clinicians cannot use a patient's coronal alignment phenotype to estimate their tibial slope. For surgical planning in total knee arthroplasty, this necessitates independent, comprehensive 3D assessment of both coronal and sagittal characteristics rather than relying on coronal alignment patterns alone.

THE STABILITY OF PAIN PHENOTYPES IN PEOPLE WITH HAND OSTEOARTHRITIS - RESULTS FROM THE NOR-HAND STUDY.

This Norwegian study aimed to identify distinct pain phenotypes in hand osteoarthritis patients and examine how stable these phenotypes remain over time using a comprehensive multidimensional pain assessment framework. The researchers analyzed 213 participants (mostly women, mean age 61 years) at baseline and 3-year follow-up, using latent transition analyses to classify patients based on pain severity, neuropathic-like pain, fatigue, sleep quality, psychological symptoms, pain catastrophizing, and quantitative sensory testing.

The analysis identified four distinct pain phenotypes that differed in pain severity and psychosocial burden, with most participants (80%) remaining in the same phenotype category over the 3-year period, though phenotype stability varied considerably (probability range 0.48-0.95). Notably, when patients did transition between phenotypes, they typically moved to less severe pain categories (73-80% of transitions), showing greater improvements in pain and psychosocial measures compared to those who remained stable.

These findings suggest that hand OA patients can be meaningfully categorized into distinct pain phenotypes that may guide personalized treatment approaches, though clinicians should recognize that some patients' phenotypes may change over time, often in a favorable direction.

DISRUPTING THE SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE-M1MACROPHAGE FEEDBACK LOOP IN SYNOVITIS USING DUAL NANO-SWITCHES TO RESTORE JOINT HOMEOSTASIS.

This study aimed to develop a novel dual nanomedicine approach to disrupt the harmful feedback loop between senescent cells and inflammatory macrophages that drives osteoarthritis progression. The researchers used bioinformatics analysis combined with clinical and animal data to design a treatment platform consisting of two components: synovium-targeting liposomes that deliver drugs to clear senescent fibroblasts, and M2 macrophage-derived exosomes that convert pro-inflammatory M1 macrophages into tissue-repairing M2 macrophages. In rat osteoarthritis models, this dual approach achieved impressive results with a 73.53% reduction in synovitis and 75.00% reduction in cartilage damage scores by simultaneously targeting both senescent cells and inflammatory macrophages.

These findings suggest that osteoarthritis phenotypes characterized by high levels of synovial inflammation and senescent cell burden may benefit from combination therapies that address multiple pathological mechanisms simultaneously, rather than single-target approaches. While this represents promising pre-clinical research, the implications for current physiotherapy and clinical management remain to be established through human trials, though it may eventually inform patient stratification strategies for identifying those with inflammation-driven disease phenotypes.

CORONAL ALIGNMENT IN INDIAN OSTEOARTHRITIC KNEES: PREDOMINANCE OF VARUS APEX-DISTAL PHENOTYPES HIGHLIGHTS POPULATION-SPECIFIC ALIGNMENT PATTERNS.

This study aimed to characterize knee alignment patterns in Indian patients with osteoarthritis using the Coronal Plane Alignment of the Knee (CPAK) classification system and evaluate outcomes after robotic-assisted knee replacement. Researchers analyzed preoperative X-rays from 947 severely arthritic knees in 604 Indian patients, measuring alignment angles and classifying knees into nine distinct phenotypes based on overall limb alignment and joint line orientation.

The findings revealed a striking predominance of varus (inward-angled) alignment, affecting 88.2% of knees, with the majority (78.7%) exhibiting CPAK Type I phenotype characterized by varus alignment with an apex-distal joint line pattern - a distribution that appears unique to this Indian population compared to Western cohorts. Following surgery using a functional alignment approach that preserved native anatomy where possible, 60% of Type I knees maintained their natural alignment within acceptable limits, while patients showed significant improvements in pain and function scores at six months.

These population-specific alignment patterns highlight the importance of tailoring surgical approaches to regional anatomical variations, suggesting that physiotherapy and rehabilitation protocols may also need to account for these distinct phenotypes when managing Indian patients with knee osteoarthritis.

AI-Generated Summaries: Osteoarthritis Phenotypes

📊 Overarching Synthesis

Osteoarthritis Phenotyping: Evidence Synthesis from 889 Articles

SECTION A: FOR PHYSIOTHERAPISTS

Identified OA Phenotypes at a Glance

Pain-Based Phenotypes:

Inflammatory Phenotypes:

Structural Phenotypes:

Metabolic Phenotypes:

Biomechanical Phenotypes:

General Overview

Phenotype Details

Classification Methods

Joint-Specific Considerations

Implications for Physiotherapy Management

Prognostic Value

Gaps and Future Directions

SECTION B: FOR PATIENTS

Your OA Type Matters - Simple Phenotype Guide

Pain-Focused Types:

Inflammation Types:

Body Chemistry Types:

Joint Shape Types:

Understanding Your Arthritis

Why This Matters for Your Treatment

What This Means Going Forward

Arthrose-Phänotypisierung: Evidenzsynthese aus 889 Artikeln

ABSCHNITT A: FÜR PHYSIOTHERAPEUTEN

Identifizierte Arthrose-Phänotypen im Überblick

Allgemeine Übersicht

Phänotyp-Details

Klassifikationsmethoden

Gelenkspezifische Überlegungen

Implikationen für das physiotherapeutische Management

Prognostischer Wert

Lücken und zukünftige Richtungen

ABSCHNITT B: FÜR PATIENTEN

Ihr Arthrose-Typ ist wichtig - Einfacher Phänotyp-Leitfaden

Ihre Arthritis verstehen

Warum das für Ihre Behandlung wichtig ist

Was das für die Zukunft bedeutet

Phénotypage de l'Arthrose : Synthèse des Preuves Issues de 889 Articles

SECTION A : POUR LES KINÉSITHÉRAPEUTES

Phénotypes d'Arthrose Identifiés - Vue d'Ensemble

Phénotypes Basés sur la Douleur :

Phénotypes Inflammatoires :

Phénotypes Structurels :

Phénotypes Métaboliques :

Phénotypes Biomécaniques :

Aperçu Général

Détails des Phénotypes

Méthodes de Classification

Considérations Spécifiques aux Articulations

Implications pour la Prise en Charge Kinésithérapique

Valeur Pronostique

Lacunes et Directions Futures

SECTION B : POUR LES PATIENTS

Votre Type d'Arthrose Compte - Guide Simple des Phénotypes

Types Centrés sur la Douleur :

Types Inflammatoires :

Types de Chimie Corporelle :

Types de Forme Articulaire :

Comprendre Votre Arthrose

Pourquoi C'est Important pour Votre Traitement

Ce Que Cela Signifie pour l'Avenir