Osteoarthritis and Cartilage最新文献

{"title":"Elevated expression of Piezo1 activates the cGAS-STING pathway in chondrocytes by releasing mitochondrial DNA.","authors":"Lin Sun, Yao Wang, Tianyou Kan, Han Wang, Junqi Cui, Liao Wang, Chenglei Liu, Hanjun Li, Zhifeng Yu, Mengning Yan","doi":"10.1016/j.joca.2025.02.778","DOIUrl":"10.1016/j.joca.2025.02.778","url":null,"abstract":"<p><strong>Objective: </strong>Abnormal mechanical stress is a key factor in osteoarthritis (OA) pathogenesis. This study aims to investigate the role of the mechanosensitive ion channel Piezo1 in activating the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway and its contribution to cartilage degradation in OA.</p><p><strong>Methods: </strong>We conducted both in vivo and in vitro experiments. In vitro, chondrocytes were subjected to mechanical stress, and Piezo1 expression, calcium ion (Ca²⁺) influx, and mitochondrial permeability changes were analyzed. In vivo, Piezo1 conditional knockout (Col2a1^CreERT; Piezo1^flox/flox) mice were used to assess the activation of the cGAS-STING pathway and cartilage degradation. Additionally, the effects of STING inhibitors on inflammation and OA progression were evaluated.</p><p><strong>Results: </strong>Mechanical stress significantly increased Piezo1 expression and Ca²⁺ influx in chondrocytes, leading to mitochondrial Ca²⁺ overload and mitochondrial DNA (mtDNA) release. This triggered activation of the cGAS-STING pathway (9.35[95%Confidence Interval (CI) 1.378 to 18.032], n=3 biologically independent samples), resulting in inflammatory responses (4.185[95%CI 0.411 to 8.168], n=3 biologically independent samples). In Piezo1 knockout mice, cGAS-STING activation (-7.23[95%CI -10.52 to -3.89], n=6) and cartilage degradation (Osteoarthritis Research Society International (OARSI) grade; -3.651[95%CI -5.562 to -1.681] n=6) were reduced. STING inhibitors effectively decreased inflammation (-8.95[95%CI -17.24 to -1.31], n=3 biologically independent samples) and slowed OA progression (OARSI grade; -2.76 [95%CI -4.37 to -1.08], n=6) in both in vivo and in vitro models.</p><p><strong>Conclusions: </strong>Mechanical stress induces mtDNA release via Piezo1 activation, which triggers the cGAS-STING pathway and exacerbates cartilage degradation. Targeting Piezo1 or the cGAS-STING pathway may offer a promising therapeutic strategy to reduce inflammation and protect cartilage in OA.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468448","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}

{"title":"The prevalence of primary cam morphology in early adolescents from the general population: A population-based study (Generation R).","authors":"Delong Chen, Fleur Boel, Pim van Klij, Michiel M A van Buuren, Sita M A Bierma-Zeinstra, Rintje Agricola","doi":"10.1016/j.joca.2025.02.775","DOIUrl":"10.1016/j.joca.2025.02.775","url":null,"abstract":"<p><strong>Objective: </strong>Small studies in athletes showed that primary cam morphology (PCM) gradually develops during skeletal growth. However, the prevalence of PCM in early adolescents is poorly understood. We aimed to estimate the overall and birth-assigned sex-specific prevalence of PCM in early adolescents from the general population.</p><p><strong>Design: </strong>We cross-sectionally analyzed data from the Generation R cohort, an ongoing population-based prospective cohort study from early fetal life onward from Rotterdam, the Netherlands. High-resolution dual-energy x-ray absorptiometry scans were performed on the right hip of participants around the age of 13 years. The alpha angle (AA) and triangular index ratio (TIR) were automatically measured. We defined PCM by a validated AA threshold ≥ 60° or a TIR threshold ≥ 1.05. The overall and birth-assigned sex-specific prevalence of PCM was reported as a percentage with 95% confidence interval (CI).</p><p><strong>Results: </strong>The median age of the 4477 early adolescents included in this analysis was 13.5 years (2.5th - 97.5th percentile, 13.2 - 14.6) with 2166 (48.4%) being males. The overall prevalence of PCM (AA ≥ 60° or TIR ≥ 1.05) was 3.5% (95% CI, 2.9-4.0%). Male and female adolescents had a similar prevalence of PCM: 3.9% (95% CI, 3.1-4.7%) vs 3.0% (95% CI, 2.3-3.7%).</p><p><strong>Conclusions: </strong>The overall prevalence of PCM was 3.5% in early adolescents from the general population in the Netherlands. The prevalence of PCM was similar between male and female early adolescents.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458752","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}

{"title":"Response to the commentary on \"Surgical restabilization reduces the progression of post-traumatic osteoarthritis initiated by ACL rupture in mice\".","authors":"Blaine A Christiansen, Yu-Yang Lin, Cassandra A Lee","doi":"10.1016/j.joca.2025.02.772","DOIUrl":"10.1016/j.joca.2025.02.772","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425897","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}

{"title":"Comment on: 'Surgical restabilization reduces the progression of post-traumatic osteoarthritis initiated by ACL rupture in mice' (Lin et al., 2024).","authors":"Tazio Maleitzke, Johanna Bolander, Ali Mobasheri, Florian N Fleckenstein, Felix Eckstein, Nicholas M Brisson, Tobias Winkler","doi":"10.1016/j.joca.2025.02.002","DOIUrl":"10.1016/j.joca.2025.02.002","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414714","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}

{"title":"EZH2 inhibits senescence-associated inflammation and attenuates intervertebral disc degeneration by regulating the cGAS/STING pathway via H3K27me3.","authors":"Jianrui Zheng, Zetao Ma, Pei Liu, Jiewen Wei, Shaoxiong Min, Ying Shan, Jianlin Zhang, Ye Li, Lixiang Xue, Zhen Tan, Deli Wang","doi":"10.1016/j.joca.2025.02.771","DOIUrl":"10.1016/j.joca.2025.02.771","url":null,"abstract":"<p><strong>Objective: </strong>Senescent nucleus pulposus mesenchymal stem cells (NPMSCs) are key instigators of local chronic inflammation and disruptions in nucleus pulposus tissue repair in intervertebral disc degeneration (IVDD). This study aimed to investigate the interplay between EZH2 and NPMSCs senescence-associated inflammation.</p><p><strong>Methods: </strong>Nucleus pulposus samples were collected from IVDD patients (n = 15, F/M = 7/8, average age 47.9 (21-72) year-old). Multiplex immunohistochemistry was conducted to detect the expression of EZH2 and the cGAS/STING pathway. Subsequently, NPMSCs were isolated from 7 patients (n = 7, F/M = 4/3, average age 49.4 (36-68) year-old). After treatment with tert-butyl hydroperoxide and lentivirus-overexpression-EZH2 (Lv-OE-EZH2), real time fluorescent quantitative PCR, immunofluorescence, western blot, and ChIP were used to detect the expression of EZH2 and the cGAS/STING pathway. Micro-CT, magnetic resonance imaging, and histological staining were performed to assess the therapeutic effects of Lv-OE-EZH2 and a STING inhibitor on rat IVDD. All experiment designs were independent.</p><p><strong>Results: </strong>In both human nucleus pulposus tissues and an in vitro cell model, EZH2 expression decreased while the cGAS/STING pathway became activated in senescent NPMSCs. ChIP assays and Lv-OE-EZH2 experiments validated that EZH2 epigenetically inhibited STING expression via H3K27me3, thereby impairing the cGAS/STING pathway and attenuating senescence-associated inflammation. Moreover, overexpression of EZH2 (Pfirrmann grade means difference -1.375, p = 0.0089) and inhibition of STING effectively attenuated rat IVDD.</p><p><strong>Conclusion: </strong>The decreased expression of EZH2 in senescent NPMSCs promotes senescence-associated inflammation and the progression of IVDD, possibly by relieving the transcriptional inhibition of STING and enabling the activation of the cGAS/STING pathway.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409848","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}

{"title":"Relation of pain sensitization to knee loading during walking in people with knee osteoarthritis.","authors":"Ehyun Kim, Tuhina Neogi, Soyoung Lee, Deepak Kumar","doi":"10.1016/j.joca.2025.01.005","DOIUrl":"10.1016/j.joca.2025.01.005","url":null,"abstract":"<p><strong>Objective: </strong>To examine the association of pain sensitization with knee joint loading during walking in people with knee osteoarthritis (OA).</p><p><strong>Method: </strong>For this cross-sectional study, we used baseline data from participants with symptomatic knee OA (n=104) enrolled in two clinical trials. We used pressure pain threshold (PPT) at the knee and wrist to assess sensitization. Using gait analyses during walking, we derived peaks and impulse of knee adduction moment (KAM) and knee flexion moment, and frontal and sagittal plane range of motion during stance. We used an Analysis of Covariance (ANCOVA) adjusted for age, sex, body height, and body weight to examine associations of PPT (sex-specific tertiles) with gait outcomes. Sensitivity analyses included additional adjustment for gait speed.</p><p><strong>Results: </strong>For knee PPT, the lowest tertile had a lower 1st peak of KAM (∆=9.1 Nm [95% CI; 0.3, 17.9]) compared to the highest tertile. For wrist PPT, when compared to the highest tertile, the lowest tertile had a lower 1st peak of KAM (∆=9.1 Nm [1.3, 16.8]), a lower 2nd peak of KAM (∆=7.5 Nm [0.5, 14.6]), and a lower KAM impulse (∆=1.7 Nm*s [0.1, 3.2]), while the middle tertile also had a lower 2nd peak of KAM (∆=8.0 Nm [0.7, 15.4]) and a lower KAM impulse (∆=2.0 Nm*s [0.4, 3.6]). The effect sizes for other gait measures were small and clinically not meaningful. These effect sizes remained similar after adjusting for gait speed.</p><p><strong>Conclusion: </strong>Greater pain sensitivity, as assessed by PPT, was related to lower frontal plane joint loading during walking. These findings may reflect a motor adaptation to nociceptive alterations in this population.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365418","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}

{"title":"Effect of arthroscopic partial meniscectomy on structural degeneration of the knee – A 5-year MRI-based follow-up of the placebo-surgery controlled FIDELITY (Finnish Degenerative Meniscus Lesion Study) trial","authors":"Niko Sillanpää ,&nbsp;Marika Iivanainen ,&nbsp;Aleksandra Turkiewicz ,&nbsp;Raine Sihvonen ,&nbsp;Mika Paavola ,&nbsp;Simo Taimela ,&nbsp;Teppo L.N. Järvinen ,&nbsp;Martin Englund","doi":"10.1016/j.joca.2024.09.003","DOIUrl":"10.1016/j.joca.2024.09.003","url":null,"abstract":"<div><h3>Objective</h3><div>To assess the 5-year effects of arthroscopic partial meniscectomy (APM) vs. placebo surgery on the development of the structural changes of the knee by magnetic resonance imaging (MRI).</div></div><div><h3>Design</h3><div>This multicentre, randomized, participant- and outcome-assessor-blinded, placebo-surgery-controlled trial was carried out in Finland. We randomized 146 adults, mean age 52 years (range 35 to 65) to undergo either APM or placebo surgery. The subjects had symptoms of degenerative medial meniscus tear, a tear verified in MRI and arthroscopy, and no advanced osteoarthritis at baseline. We compared the baseline and 5-year follow-up MRIs using MRI Osteoarthritis Knee Score scoring to derive subregional data on cartilage damage, osteophytes and bone marrow lesions (BMLs). Progression of structural cartilage changes analyzed per subregion was the main outcome, that of osteophytes and BMLs secondary outcomes. We analyzed the progression with multilevel logistic regression model on subregion-level data, adjusted for randomization stratification factors, and using robust standard errors.</div></div><div><h3>Results</h3><div>Sixty-three (90%) subjects in the APM and 73 (96%) in the placebo-surgery group had MRI at both time points. The adjusted odds ratio (APM vs. placebo-surgery) was 1.31 (95% confidence interval 0.81, 1.94) for progression of cartilage damage, 2.86 (1.16, 6.21) for osteophytes, and 1.43 (0.84, 2.43) for BMLs.</div></div><div><h3>Conclusions</h3><div>We found a slightly greater risk for progression of osteophytes in the APM group compared to the placebo-surgery group at 5 years after surgery.</div></div><div><h3>Trial registration</h3><div>ClinicalTrials.gov (NCT01052233 and NCT00549172).</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"33 2","pages":"Pages 276-282"},"PeriodicalIF":7.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein folding dependence on selenoprotein M contributes to steady cartilage extracellular matrix repressing ferroptosis via PERK/ATF4/CHAC1 axis","authors":"Yitong Zhao ,&nbsp;Ying Zheng ,&nbsp;Han Li ,&nbsp;Yao Li ,&nbsp;Ru Wang ,&nbsp;Yongsong Cai ,&nbsp;Haishi Zheng ,&nbsp;Xinyu Huo ,&nbsp;Jiajun Ren ,&nbsp;Dongxian Guo ,&nbsp;Rui Luo ,&nbsp;Xinyao Wu ,&nbsp;Jingyi Lu ,&nbsp;Qingxin Song ,&nbsp;Yan Zhang ,&nbsp;Chenxing Ma ,&nbsp;Lu Wang ,&nbsp;Runyuan Wang ,&nbsp;Jing Wang ,&nbsp;Yingli He ,&nbsp;Shemin Lu","doi":"10.1016/j.joca.2024.10.005","DOIUrl":"10.1016/j.joca.2024.10.005","url":null,"abstract":"<div><h3>Objective</h3><div>Initiation of endoplasmic reticulum (ER) stress is pivotal to the advancement of osteoarthritis (OA). We aimed to explore the function of ER-resident selenoprotein M (SELM) in cartilage-forming chondrocytes, investigating how SELM participates in cartilage extracellular matrix (ECM) metabolism and ER stress modulation.</div></div><div><h3>Methods</h3><div>Articular cartilage samples with knee OA undergoing total knee arthroplasty were categorised into OA-smooth and OA-damaged groups, with primary chondrocytes extracted from smooth areas. Destabilization of the medial meniscus was induced in male C57BL6/J mice, with sham operations on the left knee as controls. After 8 weeks, knee joint tissues were collected for analysis. Histology and immunohistochemistry examined cartilage damage. Molecular biology techniques investigated how SELM affects ECM metabolism and ER stress regulation. RNA sequencing revealed the pathway changes after SELM intervention. AlphaFold demonstrated how SELM interacts with other molecules. Cultured cartilage explants helped determine the effects of SELM supplementation.</div></div><div><h3>Results</h3><div>SELM expression was reduced in the damaged cartilage. Increasing SELM levels positively impacted ECM equilibrium. Decreasing SELM expression activated genes linked to degenerative ailments and impaired the cellular response to misfolded proteins, initiating the PERK/P-EIF2A/ATF4 pathway and exacerbating GSH/GSSG imbalance via the ATF4/CHAC1 axis. SELM likely participated in protein folding and modification by leveraging its thioredoxin domains. In vitro SELM supplementation mitigated IL-1β effects on damaged cartilage explants and suppressed beneficial chondrocyte phenotypes.</div></div><div><h3>Conclusions</h3><div>Our results confirm the involvement of SELM in ER stress-induced cartilage damage as well as protein folding, pointing to new directions in molecular therapy for degenerative diseases.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"33 2","pages":"Pages 261-275"},"PeriodicalIF":7.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammaging contributes to osteoarthritis development and human microbiota variations and vice versa: A systematic review","authors":"Miruna G. Gaspar ,&nbsp;Carmen Núñez-Carro ,&nbsp;Margarita Blanco-Blanco ,&nbsp;Francisco J. Blanco ,&nbsp;María C. de Andrés","doi":"10.1016/j.joca.2024.11.005","DOIUrl":"10.1016/j.joca.2024.11.005","url":null,"abstract":"<div><h3>Objective</h3><div>To report evidence on microbiota and its relationship with inflammaging, the innate immune system and osteoarthritis (OA) in human patients.</div></div><div><h3>Design</h3><div>A systematic review was performed in accordance with PRISMA and following the PICO model. Web of Science, Scopus, Cochrane Library for clinical trials and PubMed were searched. The analysis was focused on human OA patients, and the outcome was mainly microbiota identification, improvement or deterioration of OA pain, stiffness or inflammation.</div></div><div><h3>Results</h3><div>After screening, 24 studies fulfilled the inclusion criteria. There is not a standardised procedure yet, as microbiota analysis in OA is relatively new. The 16S rRNA gene is the most used in bacterial phylogeny and taxonomy studies as it is highly conserved. Selected articles hypothesise about the correlation between the altered composition of the gut microbiota and OA severity, which seems to affect the immune composition by disrupting gut permeability and releasing pro-inflammatory factors. Five preliminary clinical trials used pro-prebiotics to treat OA patients, and although their results are not conclusive and the methodology needs to be improved, it might indicate a favourable approach for further studies in the prevention of OA.</div></div><div><h3>Conclusions</h3><div>Several hypotheses have been made on the associations between microbiota changes and inflammation. They mainly advocate that those changes in the gastrointestinal tract affect gut permeability, which alters the immune system, leading to OA progression. Research advances, along with the continual growth and improvement of technology, mark this ‘<em>microbiota-inflammaging-OA</em>' axis as a promising line of investigation.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"33 2","pages":"Pages 218-230"},"PeriodicalIF":7.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis based on large randomized trials: A systematic review and network meta-analysis","authors":"Tiago V. Pereira ,&nbsp;Pakeezah Saadat ,&nbsp;Pavlos Bobos ,&nbsp;Samir M. Iskander ,&nbsp;Nicolas S. Bodmer ,&nbsp;Martina Rudnicki ,&nbsp;Henry Dan Kiyomoto ,&nbsp;Thais Montezuma ,&nbsp;Matheus O. Almeida ,&nbsp;Rishi Bansal ,&nbsp;Pai-Shan Cheng ,&nbsp;Jason W. Busse ,&nbsp;Alex J. Sutton ,&nbsp;Peter Tugwell ,&nbsp;Gillian A. Hawker ,&nbsp;Peter Jüni ,&nbsp;Bruno R. da Costa","doi":"10.1016/j.joca.2024.08.014","DOIUrl":"10.1016/j.joca.2024.08.014","url":null,"abstract":"<div><h3>Objective</h3><div>To quantify the effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis (OA) through a systematic review and Bayesian random-effects network meta-analysis.</div></div><div><h3>Design</h3><div>We searched CENTRAL and regulatory agency websites (inception-2023) for large, English-language, randomized controlled trials (RCTs) (≥100 patients/group) examining any intra-articular intervention. Primary outcome: pain intensity. Secondary outcomes: physical function and safety outcomes. Pain and function outcomes were analyzed at 2, 6, 12, 24, and 52 weeks post-randomization, and presented as standardized mean differences (SMDs) (95% credible intervals, 95% CrI). The prespecified minimal clinically important between-group difference (MID) was −0.37 SMD. Safety outcomes were presented as odds ratios (OR) (95% CrI).</div></div><div><h3>Findings</h3><div>Among 57 RCTs (22,795 participants) examining 18 intra-articular interventions, usual care or placebo, treatment effects were larger in 35 high-risk–of-bias trials than in 22 low/unclear-risk-of-bias trials. In the main analysis (excluding high-risk-of-bias trials), triamcinolone had the highest probabilities of reaching the MID at weeks 2 and 6 (75.3% and 90%, respectively) with corresponding SMDs of −0.48 (95% CrI,−0.85 to −0.10) and −0.53 (95% CrI,−0.79 to −0.27) compared to placebo (1 trial). The complex homeopathic products Tr14/Ze14 showed therapeutic potential at week 6 compared to placebo (SMD:−0.42, 95% CrI,−0.71 to −0.11, 63.5% probability of reaching the MID, 1 trial). Hyaluronic acid had no effect on pain (SMD:-0.04, 95% CrI,−0.19 to 0.11, 11 trials) but a higher risk of dropouts due to adverse events (OR: 2.01, 95% CrI,1.08 to 3.77) and serious adverse events (OR: 1.86, 95% CrI, 1.16 to 3.03) than placebo.</div></div><div><h3>Conclusion</h3><div>Triamcinolone had the highest probabilities to have a treatment effect beyond the MID at weeks 2–6. Large RCTs with lower risk of bias indicate that the effects of 16 intra-articular interventions in knee or hip OA were smaller than the MID, and that most were consistent with placebo effects. Lack of evidence of long-term effectiveness underscores the need for further research beyond 24 weeks.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"33 2","pages":"Pages 207-217"},"PeriodicalIF":7.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}