Pub Date : 2026-01-09DOI: 10.1016/j.joca.2025.12.025
Sarah K Jachim,Divya Venkatasubramanian,Gayani Senevirathne,Andrew S Zhu,Concetta S Vitale,Delmy L Melendez,Cheng-Hai Zhang,Andrew B Lassar,Terence D Capellini,April M Craft
OBJECTIVECompromises to the integrity of articular cartilage, whether genetic, post-traumatic or age-related, lead to debilitating chronic degenerative diseases including osteoarthritis. In this study, our objective was to leverage multiomic and spatial transcriptomic datasets to identify gene regulatory networks that drive human articular cartilage cell fate, and build a foundation from which novel therapeutics to overcome degenerative disease could be developed.DESIGNWe jointly profiled the transcriptome and open chromatin regions in individual nuclei recovered from distal femora at 2 fetal timepoints and performed high-definition spatial transcriptomics at an additional timepoint. We established a human pluripotent stem cell platform to interrogate the function of computationally predicted transcription factors during human chondrocyte differentiation.RESULTSWe computationally predicted gene regulatory networks governing chondrocyte subsets comprising the human distal femur during development. Following functional analysis of two transcription factors predicted to function in the superficial zone, CREB5 and NFATC2, using our in vitro experimental platform, we found both have the potential to reprogram growth plate cartilage and induce features of articular cartilage. We further identified new biological roles for CREB5 related to ECM organization and taxis.CONCLUSIONSWe expect new regulatory networks we uncovered to be important for promoting cartilage health and treating disease, and our platform to be a useful tool for studying cartilage development and homeostasis in vitro. The ability to reprogram chondrocytes toward an articular-like fate has significant therapeutic potential to treat degenerative joint diseases.
{"title":"Leveraging single cell multiomic analyses to identify gene regulatory networks that drive human articular cartilage cell fate.","authors":"Sarah K Jachim,Divya Venkatasubramanian,Gayani Senevirathne,Andrew S Zhu,Concetta S Vitale,Delmy L Melendez,Cheng-Hai Zhang,Andrew B Lassar,Terence D Capellini,April M Craft","doi":"10.1016/j.joca.2025.12.025","DOIUrl":"https://doi.org/10.1016/j.joca.2025.12.025","url":null,"abstract":"OBJECTIVECompromises to the integrity of articular cartilage, whether genetic, post-traumatic or age-related, lead to debilitating chronic degenerative diseases including osteoarthritis. In this study, our objective was to leverage multiomic and spatial transcriptomic datasets to identify gene regulatory networks that drive human articular cartilage cell fate, and build a foundation from which novel therapeutics to overcome degenerative disease could be developed.DESIGNWe jointly profiled the transcriptome and open chromatin regions in individual nuclei recovered from distal femora at 2 fetal timepoints and performed high-definition spatial transcriptomics at an additional timepoint. We established a human pluripotent stem cell platform to interrogate the function of computationally predicted transcription factors during human chondrocyte differentiation.RESULTSWe computationally predicted gene regulatory networks governing chondrocyte subsets comprising the human distal femur during development. Following functional analysis of two transcription factors predicted to function in the superficial zone, CREB5 and NFATC2, using our in vitro experimental platform, we found both have the potential to reprogram growth plate cartilage and induce features of articular cartilage. We further identified new biological roles for CREB5 related to ECM organization and taxis.CONCLUSIONSWe expect new regulatory networks we uncovered to be important for promoting cartilage health and treating disease, and our platform to be a useful tool for studying cartilage development and homeostasis in vitro. The ability to reprogram chondrocytes toward an articular-like fate has significant therapeutic potential to treat degenerative joint diseases.","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"82 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-08DOI: 10.1016/j.joca.2025.12.024
Armaghan Mahmoudian
{"title":"Persistent symptoms after ACL injury - clarifying the link to OA.","authors":"Armaghan Mahmoudian","doi":"10.1016/j.joca.2025.12.024","DOIUrl":"https://doi.org/10.1016/j.joca.2025.12.024","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"20 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-07DOI: 10.1016/j.joca.2025.12.015
Matt J Barter,Jamie Soul,Kathleen Cheung,Julia Falk,Karina Putri,Adam J Farrier,Andreas Panagiotopoulos,David J Deehan,Louise N Reynard,David A Young
OBJECTIVECell-specific gene expression programs are mediated by interactions between enhancers, transcription factors and gene promoters. Access to the DNA is regulated by the presence and modification state of chromatin. This study sought to reveal the chromatin accessibility of the cartilage chondrocyte genome and identify changes that occur in accessibility during both development from mesenchymal stem cells (MSC) and in osteoarthritis (OA).METHODAssay for Transposase-Accessible Chromatin using Sequencing (ATAC-seq) was performed on bone-marrow-MSC and MSC-derived differentiated chondrocytes, as well as primary chondrocytes isolated from 16 patients undergoing total hip replacement because of OA or due to a neck of femur fracture.RESULTSDuring MSC chondrogenesis we identified 138005 open chromatin regions, with 20979 regions undergoing increased accessibility. De novo established accessible regions were enriched at enhancer regions, defined previously by ChIP-seq, with key cartilage genes experiencing substantial chromatin reconfiguration often overlapping with SOX9 binding sites. In hip chondrocytes we identified 115295 open chromatin regions, of which 1383 and 573 were more or less differentially accessible in OA. Comparison with a single cell ATAC-seq ATLAS identified accessible regions restricted to chondrocytes and established during chondrogenesis. Accessible regions were mapped to 320 OA-associated single nucleotide variants, many of which become accessible during chondrocyte development.CONCLUSIONSThis study illustrates the establishment of the chondrocyte chromatin landscape and identifies enhancer regions correlated with the cartilage transcriptome and associated with variants linked with cartilage disease OA.
{"title":"Chromatin accessibility in MSC chondrogenesis, adult hip cartilage chondrocytes and osteoarthritis.","authors":"Matt J Barter,Jamie Soul,Kathleen Cheung,Julia Falk,Karina Putri,Adam J Farrier,Andreas Panagiotopoulos,David J Deehan,Louise N Reynard,David A Young","doi":"10.1016/j.joca.2025.12.015","DOIUrl":"https://doi.org/10.1016/j.joca.2025.12.015","url":null,"abstract":"OBJECTIVECell-specific gene expression programs are mediated by interactions between enhancers, transcription factors and gene promoters. Access to the DNA is regulated by the presence and modification state of chromatin. This study sought to reveal the chromatin accessibility of the cartilage chondrocyte genome and identify changes that occur in accessibility during both development from mesenchymal stem cells (MSC) and in osteoarthritis (OA).METHODAssay for Transposase-Accessible Chromatin using Sequencing (ATAC-seq) was performed on bone-marrow-MSC and MSC-derived differentiated chondrocytes, as well as primary chondrocytes isolated from 16 patients undergoing total hip replacement because of OA or due to a neck of femur fracture.RESULTSDuring MSC chondrogenesis we identified 138005 open chromatin regions, with 20979 regions undergoing increased accessibility. De novo established accessible regions were enriched at enhancer regions, defined previously by ChIP-seq, with key cartilage genes experiencing substantial chromatin reconfiguration often overlapping with SOX9 binding sites. In hip chondrocytes we identified 115295 open chromatin regions, of which 1383 and 573 were more or less differentially accessible in OA. Comparison with a single cell ATAC-seq ATLAS identified accessible regions restricted to chondrocytes and established during chondrogenesis. Accessible regions were mapped to 320 OA-associated single nucleotide variants, many of which become accessible during chondrocyte development.CONCLUSIONSThis study illustrates the establishment of the chondrocyte chromatin landscape and identifies enhancer regions correlated with the cartilage transcriptome and associated with variants linked with cartilage disease OA.","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"29 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1016/j.joca.2025.12.022
Bahaeddine Tilouche, Stephanie Farhat, Spencer Short, Mariya Somyk, Isabel Horton, Paul Beaulé, Sasha Carsen, George Grammatopoulos, Daniel L. Coutu
{"title":"Cellular and molecular changes in the human osteoarthritic and aging hip pulvinar","authors":"Bahaeddine Tilouche, Stephanie Farhat, Spencer Short, Mariya Somyk, Isabel Horton, Paul Beaulé, Sasha Carsen, George Grammatopoulos, Daniel L. Coutu","doi":"10.1016/j.joca.2025.12.022","DOIUrl":"https://doi.org/10.1016/j.joca.2025.12.022","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"15 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145902561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-03DOI: 10.1016/j.joca.2025.12.023
Fraser L. Collins, Alexander J Knights, Tristan Maerz, Anke J. Roelofs, Cosimo De Bari
{"title":"Synovial fibroblast responses to different types of injury resulting in cartilage repair or osteoarthritis","authors":"Fraser L. Collins, Alexander J Knights, Tristan Maerz, Anke J. Roelofs, Cosimo De Bari","doi":"10.1016/j.joca.2025.12.023","DOIUrl":"https://doi.org/10.1016/j.joca.2025.12.023","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.joca.2025.01.006
Sophia N. Ziemian , Adrien Y. Antoinette , Ana Witkowski , Miguel Otero , Steven R. Goldring , Mary B. Goldring , Marjolein C.H. van der Meulen
Objective
While physiological loads maintain cartilage health, both joint overload and abnormal joint mechanical loading contribute to osteoarthritis (OA) development. Here, we examined the role of abnormal mechanical loading on joint health by comparing the severity of OA development following a single overload event and repetitive joint overloads.
Method
Cyclic tibial compression was applied to the left limbs of 26-week-old male mice at a peak load of 9N for either a single bout or daily bouts to initiate OA disease. Joint damage severity was morphologically examined using histology and microcomputed tomography at 6 weeks following the start of loading. Early-stage transcriptomic responses to loading were evaluated.
Results
Joint damage was more severe at 6 weeks following a single bout of loading than after daily loading bouts. Severe cartilage damage, subchondral plate erosions, and soft tissue calcifications occurred following the single bout of loading. Daily loading bouts resulted in less severe cartilage damage and preserved subchondral plate integrity. A diverging transcriptomic response was identified in cartilage at 1 week with increased expression of fibrosis- and inflammation-related genes following a single bout of loading compared to daily loading.
Conclusions
Even applied at hyperphysiological load magnitudes known to initiate cartilage damage, repetitive loading may induce protective effects in the joint and attenuate OA progression over time relative to a single bout of loading. Our findings suggest the potential of mechanotherapies that use repetitive loading as disease-modifying treatments for OA disease.
{"title":"Joint damage is more severe following a single bout than multiple bouts of high magnitude loading in mice","authors":"Sophia N. Ziemian , Adrien Y. Antoinette , Ana Witkowski , Miguel Otero , Steven R. Goldring , Mary B. Goldring , Marjolein C.H. van der Meulen","doi":"10.1016/j.joca.2025.01.006","DOIUrl":"10.1016/j.joca.2025.01.006","url":null,"abstract":"<div><h3>Objective</h3><div>While physiological loads maintain cartilage health, both joint overload and abnormal joint mechanical loading contribute to osteoarthritis (OA) development. Here, we examined the role of abnormal mechanical loading on joint health by comparing the severity of OA development following a single overload event and repetitive joint overloads.</div></div><div><h3>Method</h3><div>Cyclic tibial compression was applied to the left limbs of 26-week-old male mice at a peak load of 9N for either a single bout or daily bouts to initiate OA disease. Joint damage severity was morphologically examined using histology and microcomputed tomography<span> at 6 weeks following the start of loading. Early-stage transcriptomic responses to loading were evaluated.</span></div></div><div><h3>Results</h3><div>Joint damage was more severe at 6 weeks following a single bout of loading than after daily loading bouts. Severe cartilage damage, subchondral plate erosions, and soft tissue calcifications occurred following the single bout of loading. Daily loading bouts resulted in less severe cartilage damage and preserved subchondral plate integrity. A diverging transcriptomic response was identified in cartilage at 1 week with increased expression of fibrosis- and inflammation-related genes following a single bout of loading compared to daily loading.</div></div><div><h3>Conclusions</h3><div>Even applied at hyperphysiological load magnitudes known to initiate cartilage damage, repetitive loading may induce protective effects in the joint and attenuate OA progression over time relative to a single bout of loading. Our findings suggest the potential of mechanotherapies that use repetitive loading as disease-modifying treatments for OA disease.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 1","pages":"Pages 58-69"},"PeriodicalIF":9.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.joca.2025.10.016
Kranti C. Rumalla , Sumanth R. Chandrupatla , Jasvinder A. Singh
Objective
To identify the presence and magnitude of total joint arthroplasty (TJA) disparities in length of stay (LOS).
Methods
The National Inpatient Sample (2016–2019) was queried for patients with primary diagnoses of osteoarthritis (OA) and primary procedure code of primary total hip arthroplasty (THA) or total knee arthroplasty (TKA). Race and ethnicity and sex variables were recoded and combined into 12 categories. We determined the effect of this combined race and sex variable on extended length of stay, controlling for potential intermediates and demographic variables, and conducted analysis of individual heterogeneity and discriminatory accuracy (AIHDA) analyses.
Results
A total of 1507,085 THAs and 2534,749 TKAs were captured during the study period. White females constituted the greatest proportion of THAs and TKAs. Nearly all minoritized race/ethnicities, regardless of sex, were at greater risk of extended length of stay (eLOS, > 3 days) compared to White males. Black females experienced the greatest disparity of eLOS [THA, aOR 2.42 (95% CI: 2.26–2.60, p<0.001); TKA, aOR 2.07 (95% CI: 1.96–2.18, p<0.001)] followed by Black males [THA, aOR 1.86 (95% CI: 1.72–2.02, p<0.001); TKA, aOR 1.89 (95% CI: 1.77–2.02, p<0.001)]. AIHDA analysis showed that race/ethnicity and sex did not significantly improve discriminatory accuracy when included in the models.
Conclusion
There are significant racial and ethnic disparities in THA/TKA hospital LOS which are both statistically and clinically significant. Social determinants of health (SDOH) continue to play a meaningful role in these outcomes, though targeting race/ethnicity and sex directly may not improve eLOS in patients.
{"title":"Intersectional racial, ethnic, and sex-based disparities in length of stay after total hip and knee arthroplasty: An analysis of national data","authors":"Kranti C. Rumalla , Sumanth R. Chandrupatla , Jasvinder A. Singh","doi":"10.1016/j.joca.2025.10.016","DOIUrl":"10.1016/j.joca.2025.10.016","url":null,"abstract":"<div><h3>Objective</h3><div>To identify the presence and magnitude of total joint arthroplasty (TJA) disparities in length of stay (LOS).</div></div><div><h3>Methods</h3><div>The National Inpatient Sample (2016–2019) was queried for patients with primary diagnoses of osteoarthritis (OA) and primary procedure code of primary total hip arthroplasty (THA) or total knee arthroplasty (TKA). Race and ethnicity and sex variables were recoded and combined into 12 categories. We determined the effect of this combined race and sex variable on extended length of stay, controlling for potential intermediates and demographic variables, and conducted analysis of individual heterogeneity and discriminatory accuracy (AIHDA) analyses.</div></div><div><h3>Results</h3><div>A total of 1507,085 THAs and 2534,749 TKAs were captured during the study period. White females constituted the greatest proportion of THAs and TKAs. Nearly all minoritized race/ethnicities, regardless of sex, were at greater risk of extended length of stay (eLOS, > 3 days) compared to White males. Black females experienced the greatest disparity of eLOS [THA, aOR 2.42 (95% CI: 2.26–2.60, p<0.001); TKA, aOR 2.07 (95% CI: 1.96–2.18, p<0.001)] followed by Black males [THA, aOR 1.86 (95% CI: 1.72–2.02, p<0.001); TKA, aOR 1.89 (95% CI: 1.77–2.02, p<0.001)]. AIHDA analysis showed that race/ethnicity and sex did not significantly improve discriminatory accuracy when included in the models.</div></div><div><h3>Conclusion</h3><div>There are significant racial and ethnic disparities in THA/TKA hospital LOS which are both statistically and clinically significant. Social determinants of health (SDOH) continue to play a meaningful role in these outcomes, though targeting race/ethnicity and sex directly may not improve eLOS in patients.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 1","pages":"Pages 160-166"},"PeriodicalIF":9.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.joca.2025.11.009
B. Steele-Turner , A.C. Gonçalves , A.I. Shepherd , H. Drummond , K. Allison , K.L. Bennell , T.A. Exell
Objective
To systematically identify the literature surrounding weight management (WM) integration into physiotherapist-led osteoarthritis (OA) care and understand the perceptions of physiotherapists, students and people with OA towards physiotherapist-led WM within OA care.
Method
Eight electronic databases (CINAHL, Cochrane, MEDLINE, PEDro, PsycInfo, Scopus, SPORTDiscus and Web of Science) were searched from inception to 2nd August 2025 to include all forms of primary and secondary research alongside grey literature. Identified records were screened by two independent reviewers against eligibility criteria. Further potentially relevant records were found via hand searching and forward citing of included studies. Data were extracted to (1) descriptively analyse and (2) thematically synthesise the included records.
Results
The search strategy delivered 1806 unique records, of which 79 records met the eligibility criteria. Four key themes were identified: (a) current integration of WM in physiotherapist-led OA care is variable, (b) there are questions regarding scope of practice amongst physiotherapists and people with OA, (c) physiotherapists often lack the confidence and skills to discuss weight and (d) further education on the complexities and delivery of WM for physiotherapists is required. A variety of terms are used in existing literature when describing physiotherapist-led WM interventions.
Conclusion
Available literature on physiotherapist-led WM for people with OA is highly heterogenous. The effectiveness of physiotherapist-led WM requires investigation in multiple settings. The feasibility of including WM education in pre-registration physiotherapy curricula should also be examined. A lack of standardised term describing WM support provided by physiotherapists should be addressed.
Registration
https:doi.org/10.17605/OSF.IO/XSA2Z
目的系统梳理有关体重管理（WM）融入物理治疗师主导的骨关节炎（OA）护理的文献，了解物理治疗师、学生和OA患者对OA护理中物理治疗师主导的WM的看法。MethodEight电子数据库（CINAHL, Cochrane， MEDLINE, PEDro, PsycInfo, Scopus， SPORTDiscus和Web of Science）从成立到2025年8月2日进行检索，包括所有形式的初级和次级研究以及灰色文献。确定的记录由两名独立的审稿人根据资格标准进行筛选。通过人工检索和对纳入研究的前引，进一步发现了潜在的相关记录。数据提取用于(1)描述性分析和(2)主题性综合纳入的记录。结果该检索策略共输出1806条唯一记录，其中符合检索条件的记录79条。确定了四个关键主题：(a)目前物理治疗师领导的OA护理中WM的整合是可变的；(b)物理治疗师和OA患者之间存在关于实践范围的问题；(c)物理治疗师通常缺乏讨论体重的信心和技能；(d)需要对物理治疗师进行关于WM复杂性和交付的进一步教育。在现有文献中，当描述物理治疗师领导的WM干预时，使用了各种术语。结论关于骨性关节炎患者物理治疗师主导的WM的现有文献存在高度异质性。物理治疗师主导的WM的有效性需要在多种情况下进行调查。在注册前理疗课程中纳入WM教育的可行性也应进行研究。缺乏描述物理治疗师提供的WM支持的标准化术语的问题应该得到解决
{"title":"Physiotherapist-led weight management for people with osteoarthritis: A scoping review","authors":"B. Steele-Turner , A.C. Gonçalves , A.I. Shepherd , H. Drummond , K. Allison , K.L. Bennell , T.A. Exell","doi":"10.1016/j.joca.2025.11.009","DOIUrl":"10.1016/j.joca.2025.11.009","url":null,"abstract":"<div><h3>Objective</h3><div>To systematically identify the literature surrounding weight management (WM) integration into physiotherapist-led osteoarthritis (OA) care and understand the perceptions of physiotherapists, students and people with OA towards physiotherapist-led WM within OA care.</div></div><div><h3>Method</h3><div>Eight electronic databases (CINAHL, Cochrane, MEDLINE, PEDro, PsycInfo, Scopus, SPORTDiscus and Web of Science) were searched from inception to 2nd August 2025 to include all forms of primary and secondary research alongside grey literature. Identified records were screened by two independent reviewers against eligibility criteria. Further potentially relevant records were found via hand searching and forward citing of included studies. Data were extracted to (1) descriptively analyse and (2) thematically synthesise the included records.</div></div><div><h3>Results</h3><div>The search strategy delivered 1806 unique records, of which 79 records met the eligibility criteria. Four key themes were identified: (a) current integration of WM in physiotherapist-led OA care is variable, (b) there are questions regarding scope of practice amongst physiotherapists and people with OA, (c) physiotherapists often lack the confidence and skills to discuss weight and (d) further education on the complexities and delivery of WM for physiotherapists is required. A variety of terms are used in existing literature when describing physiotherapist-led WM interventions.</div></div><div><h3>Conclusion</h3><div>Available literature on physiotherapist-led WM for people with OA is highly heterogenous. The effectiveness of physiotherapist-led WM requires investigation in multiple settings. The feasibility of including WM education in pre-registration physiotherapy curricula should also be examined. A lack of standardised term describing WM support provided by physiotherapists should be addressed.</div></div><div><h3>Registration</h3><div>https:doi.org/10.17605/OSF.IO/XSA2Z</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 1","pages":"Pages 121-138"},"PeriodicalIF":9.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145567206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.joca.2025.09.002
Fabio A. Simoes , Greg Scutt , Manuela Mengozzi , Simon A. Mitchell , Jacob Keen , Katherine A. Staines , Linda Troeberg , Blandine Poulet , Andrew A. Pitsillides , Lisa M. Mullen
Objective
Therapeutic potential of selective aggrecanase inhibition in osteoarthritis (OA) was previously demonstrated using a variant of endogenous tissue inhibitor of metalloproteinase-3 (TIMP-3); however, this relied on transgenic mice overexpressing TIMP-3. Here, we develop a translational approach for harnessing the aggrecanase-selective inhibitory activity of TIMP-3 using the latency associated peptide (LAP) technology.
Methods
We successfully produced and purified recombinant LAP-TIMP-3 fusion proteins and determined the pharmacokinetics of these proteins in vivo following systemic injection. Surgical and non-surgical mouse models of OA were used to establish the therapeutic potential of these proteins in reducing aggrecanase activity in mouse joints affected by OA.
Results
The presence of the LAP conferred favourable TIMP-3 pharmacokinetics, with effective delivery of LAP-TIMP-3 to knee joints after systemic injection. We find that LAP-TIMP-3 also effectively reduced aggrecanase activity in OA-affected joints, both in spontaneously-occurring OA and in the destabilisation of the medial meniscus (DMM) model of OA. We also found that reductions in aggrecanase activity in articular cartilage correlated with improved disease scores, but only in earlier stages of disease.
Conclusions
This study describes the potential of LAP-TIMP-3 as a therapeutic agent in OA, showing delivery to the cartilage of joints affected by OA after systemic administration and lower levels of the neoepitope of aggrecan in articular cartilage in mild disease (mean difference versus vehicle control for LAP-TIMP-3: 535 [95% CI: 336, 733] and for LAP-mutTIMP-3: 522 [95% CI: 323, 720] arbitrary units). These first in vivo data will inform further explorations into dose optimization and timing.
{"title":"Development of a translational strategy for using TIMP-3 to inhibit aggrecanase activity in osteoarthritis","authors":"Fabio A. Simoes , Greg Scutt , Manuela Mengozzi , Simon A. Mitchell , Jacob Keen , Katherine A. Staines , Linda Troeberg , Blandine Poulet , Andrew A. Pitsillides , Lisa M. Mullen","doi":"10.1016/j.joca.2025.09.002","DOIUrl":"10.1016/j.joca.2025.09.002","url":null,"abstract":"<div><h3>Objective</h3><div>Therapeutic potential of selective aggrecanase inhibition in osteoarthritis (OA) was previously demonstrated using a variant of endogenous tissue inhibitor of metalloproteinase-3 (TIMP-3); however, this relied on transgenic mice overexpressing TIMP-3. Here, we develop a translational approach for harnessing the aggrecanase-selective inhibitory activity of TIMP-3 using the latency associated peptide (LAP) technology.</div></div><div><h3>Methods</h3><div>We successfully produced and purified recombinant LAP-TIMP-3 fusion proteins and determined the pharmacokinetics of these proteins <em>in vivo</em> following systemic injection. Surgical and non-surgical mouse models of OA were used to establish the therapeutic potential of these proteins in reducing aggrecanase activity in mouse joints affected by OA.</div></div><div><h3>Results</h3><div>The presence of the LAP conferred favourable TIMP-3 pharmacokinetics, with effective delivery of LAP-TIMP-3 to knee joints after systemic injection. We find that LAP-TIMP-3 also effectively reduced aggrecanase activity in OA-affected joints, both in spontaneously-occurring OA and in the destabilisation of the medial meniscus (DMM) model of OA. We also found that reductions in aggrecanase activity in articular cartilage correlated with improved disease scores, but only in earlier stages of disease.</div></div><div><h3>Conclusions</h3><div>This study describes the potential of LAP-TIMP-3 as a therapeutic agent in OA, showing delivery to the cartilage of joints affected by OA after systemic administration and lower levels of the neoepitope of aggrecan in articular cartilage in mild disease (mean difference versus vehicle control for LAP-TIMP-3: 535 [95% CI: 336, 733] and for LAP-mutTIMP-3: 522 [95% CI: 323, 720] arbitrary units). These first <em>in vivo</em> data will inform further explorations into dose optimization and timing.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 1","pages":"Pages 93-104"},"PeriodicalIF":9.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.joca.2025.08.007
Xiaoqian Liu
{"title":"Air pollution and its impact on people with osteoarthritis","authors":"Xiaoqian Liu","doi":"10.1016/j.joca.2025.08.007","DOIUrl":"10.1016/j.joca.2025.08.007","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 1","pages":"Pages 16-17"},"PeriodicalIF":9.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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