{"title":"Correlation between Gut Dysbiosis, Metabolite Alterations and Erosive Hand Osteoarthritis - an observational study within the community-based Xiangya Osteoarthritis (XO) cohort.","authors":"Dongxing Xie,Yuqing Wang,Jiatian Li,Tuo Yang,Yuqing Zhang,Weiya Zhang,Michael Doherty,Yanqiu Zhu,Zidan Yang,Yilun Wang,Jie Wei,Guanghua Lei,Chao Zeng","doi":"10.1016/j.joca.2025.07.004","DOIUrl":"https://doi.org/10.1016/j.joca.2025.07.004","url":null,"abstract":"OBJECTIVESErosive hand osteoarthritis (EHOA) is an aggressive subtype of hand osteoarthritis (HOA) with unclear pathogenesis. Since gut dysbiosis and related metabolite alterations may exacerbate inflammation and accelerate bone destruction, we investigated whether these abnormalities were involved in EHOA.METHODSParticipants were drawn from the Xiangya Osteoarthritis Study. We compared gut microbial α-diversity and β-diversity between EHOA and controls (neither EHOA nor non-erosive HOA), and analyzed associations between microbial species abundance, functions, and EHOA. Targeted blood metabolomics were performed to identify microbiome-associated metabolites in EHOA. The associations between EHOA-related microbial species and blood metabolites were examine through multi-omics analyses.RESULTSAmong 1,324 participants, significant differences in α-diversity (EHOA: median=4.53, non-HOA control: median=4.16; median difference=0.37 [95%CI: 0.09-0.57], P=0.016) and β-diversity (R²=0.002 [95%CI: 0.0018-0.006], P=0.015) were observed at the species level between EHOA and controls. Participants with EHOA had a higher relative abundance of Alistipes senegalensis (β coefficient:0.17 [95%CI:0.07-0.26]) and Fournierella massiliensis (β coefficient:0.39 [95%CI:0.28-0.49]). Tryptophan metabolism was the main altered metabolic pathway. Targeted blood metabolomics showed higher levels of L-5-hydroxytryptophan (β coefficient:0.38 [95%CI:0.15-0.61]), 3-indoleglyoxylic acid (β coefficient:0.35 [95%CI:0.01-0.69]), 5-hydroxyindoleacetic acid (β coefficient:0.27 [95%CI:0.09-0.45]), indoleacrylic acid (IA) (β coefficient:0.23 [95%CI:0.001-0.46]), and serotonin (β coefficient: 0.20 [95%CI: 0.004-0.40]), alongside lower levels of L-tryptophan (β coefficient:-0.41 [95%CI:-0.75 to -0.06]) and indole-3-acetyl-aspartate (β coefficient:-1.05 [95%CI:-1.79 to -0.32]) in EHOA. IA was positively correlated with EHOA-related microbial species, particularly Alistipes senegalensis (β coefficient:0.20 [95%CI:0.14-0.27]).CONCLUSIONSA higher relative abundance of Alistipes senegalensis and alterations in tryptophan metabolites, particularly higher levels of IA, are associated with EHOA.","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"47 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594240","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}
Liya Ai,Qiusheng Shi,Mingze Du,Yikai Wang,Zhen Zhang,Jingke Du,Fangxue Zhang,Lisha Zheng,Dong Jiang
{"title":"Stem Cell Warm-Up via Biomimetic Mechanical Priming Enhances Synovial-Derived MSCs Adaptation for Meniscal Repair.","authors":"Liya Ai,Qiusheng Shi,Mingze Du,Yikai Wang,Zhen Zhang,Jingke Du,Fangxue Zhang,Lisha Zheng,Dong Jiang","doi":"10.1016/j.joca.2025.07.001","DOIUrl":"https://doi.org/10.1016/j.joca.2025.07.001","url":null,"abstract":"OBJECTIVEMesenchymal stem cell (MSCs) transplantation shows promise for meniscus repair, but their inadaptability to the in vivo mechanical environment complicates differentiation regulation. This study developed a mechanical priming strategy to enhance MSCs fibrochondrogenic differentiation and promote meniscus repair.METHODSSynovial-derived MSCs (SMSCs) were co-cultured with meniscal fibrochondrocytes and exposed to cyclic tensile strain (10%, 0.5 Hz, 4 h/day) for 5 days as a \"stem cell warm-up system\". Differentiation and mechanical adaptation were assessed through gene expression, cytoskeletal and nuclear morphology, and YAP-mediated mechanical transduction in vitro. A 2-mm meniscus defect model in New Zealand white rabbits was used, with histological analysis for repair evaluation.RESULTSMechanical priming inhibited SMSCs hypertrophy and promoted fibrochondrogenesis, with effects lasting 72 hours post-loading. Meanwhile, priming induced actin cap formation, nuclear flattening, and nuclear pore expansion, facilitating mechanical adaptation. YAP-mediated transduction was essential for the sustained upregulation of differentiation-related genes, alongside increased expression of its downstream targets, Ctgf and Cyr61. siRNA silencing of Ctgf and Cyr61 led to a downregulation of differentiation-related genes, with YAP inhibition further suppressed differentiation, underscoring its pivotal role in regulating this process. Primed SMSCs exhibited faster activation and better phenotype maintenance during secondary loading. In vivo, primed SMSCs demonstrated superior performance in meniscus regeneration, equivalent to the outcomes of growth factor-treated groups.CONCLUSIONSThis biomimetic priming system enhances MSC differentiation and mechanical adaptability, offering a clinically translatable strategy for meniscus repair and load-bearing tissue regeneration.","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"68 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578585","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":"How to treat eccentric glenohumeral osteoarthritis: more clinical vignettes do not inform us - we need knowledge.","authors":"Benjamin Zmistowski, Elizabeth Yanik","doi":"10.1016/j.joca.2025.06.006","DOIUrl":"https://doi.org/10.1016/j.joca.2025.06.006","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560730","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":"Osteoclast-secreted galectin-3 promotes articular cartilage degeneration in OVX rat via LRP1/beta-catenin axis.","authors":"Longting Chen, Haofeng Hong, Zihuan Yang, Yiming Zhong, Shang Sun, Zhuoxin Li, Chunli Song, Weishi Li, Huijie Leng","doi":"10.1016/j.joca.2025.06.013","DOIUrl":"https://doi.org/10.1016/j.joca.2025.06.013","url":null,"abstract":"<p><strong>Objective: </strong>Postmenopausal women exhibit a higher incidence of osteoarthritis (OA) than age-matched men. This study aimed to investigate the effects of osteoclasts under estrogen deficiency on chondrocytes and to elucidate the associated molecular mechanisms.</p><p><strong>Design: </strong>Rat ovariectomy-induced OA (OVX-OA) model was employed to induce bone loss and cartilage degeneration. Chondrocytes were co-cultured with osteoclasts derived from OVX or sham-operated rats. Proteomics were employed to screen proteins mediating the osteoclast-chondrocyte interaction. Co-immunoprecipitation combined with proteomics was employed to investigate the molecular mechanisms through which the screened protein induce chondrocyte dysfunction.</p><p><strong>Results: </strong>Subchondral bone loss induced osteoarthritis-like phenotypes, manifested by reduced proteoglycan content (-0.33 [95%CI: -0.47 to -0.19]) and disrupted metabolism in chondrocyte. When co-cultured with osteoclasts derived from OVX rats, chondrocytes exhibited enhanced catabolism and suppressed anabolism (ADAMTS5: 1.32 [1.082 to 1.559], MMP3: 1.44 [1.67 to 1.71], MMP13: 1.52 [1.16 to 1.88], ACAN: -0.70 [-0.92 to 0.48], COL2A1: -0.60 [-0.78 to -0.42]). These effects were reversible when osteoclasts were pretreated with the osteoclast inhibitor alendronate. We identified Galectin-3 (Gal-3) as the key mediator of osteoclast-induced chondrocyte dysfunction. Gal-3 knockdown in osteoclasts reversed detrimental effects of osteoclasts on chondrocytes. Gal-3 was found to interact with LRP1, activating the β-catenin pathway and promoting OA development.</p><p><strong>Conclusions: </strong>Osteoclast-secreted Gal-3 promotes articular cartilage degeneration in OVX rats by combining with LRP1 and activating β-catenin pathway in chondrocyte. Targeting Gal-3 could be a promising therapeutic strategy for estrogen deficiency-associated OA.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560732","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":"Is metformin for pain relief or disease modification in knee osteoarthritis?","authors":"Haowei Chen, Guangfeng Ruan, Changhai Ding","doi":"10.1016/j.joca.2025.06.012","DOIUrl":"https://doi.org/10.1016/j.joca.2025.06.012","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":7.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560731","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 ‘The association between endogenous sex hormones and knee osteoarthritis in women: a population-based cohort study’","authors":"Junjie Wang, Guoqi Cai","doi":"10.1016/j.joca.2025.06.009","DOIUrl":"https://doi.org/10.1016/j.joca.2025.06.009","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"16 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515959","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":"Beyond weight loss: GLP-1 emerges as a disease-modifying signal in osteoarthritis","authors":"Francis Berenbaum","doi":"10.1016/j.joca.2025.06.011","DOIUrl":"https://doi.org/10.1016/j.joca.2025.06.011","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"38 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337711","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":"Methodological gaps in air pollution and osteoarthritis risk research","authors":"Peng-yan Qiao, Yanli Yang, Jun-kang Zhao, Pingzhi Wang, James Cheng-Chung Wei, Li-yun Zhang","doi":"10.1016/j.joca.2025.06.010","DOIUrl":"https://doi.org/10.1016/j.joca.2025.06.010","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"38 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337712","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}
Kei Takahata, Yu-Yang Lin, Benjamin Osipov, Kohei Arakawa, Saaya Enomoto, Blaine A. Christiansen, Takanori Kokubun
{"title":"Concurrent joint contact in anterior cruciate ligament injury induces cartilage micro-injury and subchondral bone sclerosis, resulting in knee osteoarthritis","authors":"Kei Takahata, Yu-Yang Lin, Benjamin Osipov, Kohei Arakawa, Saaya Enomoto, Blaine A. Christiansen, Takanori Kokubun","doi":"10.1016/j.joca.2025.06.007","DOIUrl":"https://doi.org/10.1016/j.joca.2025.06.007","url":null,"abstract":"Anterior cruciate ligament (ACL) injury initiates post-traumatic osteoarthritis (PTOA) via two distinct processes: initial direct contact injury of the cartilage surface during ACL injury, and secondary joint instability due to the ACL deficiency. Using the well-established Compression-induced ACL-rupture and a novel Non-Compression ACL-rupture mice model, we aimed to reveal the individual effects of cartilage compression and joint instability on PTOA progression.","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"26 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337878","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":"Emapunil relieves osteoarthritis by regulating the CD14/TLR4/LY96 pathway in synovial macrophages through translocator protein 18 kDa.","authors":"Jianbin Yin,Jialuo Huang,Junfeng Wu,Lingfeng Gao,Haoran Xu,Jinjian Zhu,Hanwen Mai,Jiaxin Luo,Zihao Yao,Yuexin Li,Haobin Li,Zhikun Yuan,Daozhang Cai,Haiyan Zhang","doi":"10.1016/j.joca.2025.06.008","DOIUrl":"https://doi.org/10.1016/j.joca.2025.06.008","url":null,"abstract":"OBJECTIVEOsteoarthritis (OA), the most prevalent chronic degenerative joint disease, lacks effective therapies due to unclear pathogenesis. This study investigated the effects and mechanisms of translocator protein 18 kDa (TSPO) and its ligand emapunil in OA.METHODSTSPO expression was assessed in synovium, macrophages, and cartilage from OA mice and patients. Macrophages TSPO was manipulated via plasmid and siRNA to evaluate polarization and inflammatory responses. Molecular docking was applied to evaluate TSPO affinity was validated by molecular docking, and its therapeutic effects were tested in vitro and in vivo. RNA sequencing analyzed LPS-induced M1 macrophages treated with Emapunil.RESULTSTSPO was upregulated in OA synovium (particularly macrophages) but unchanged in cartilage. Overexpression promoted M1 polarization and proinflammatory cytokine release, while TSPO inhibition showed no significant effects. Emapunil, a potent TSPO ligand, suppressed LPS-induced M1 polarization, reduced proinflammatory cytokines, and alleviated chondrocyte destruction. Intraperitoneal Emapunil attenuated synovitis and cartilage erosion in OA mice, lowering synovitis and Osteoarthritis Research Society International scores (OARSI), reducing M1 macrophages and MMP13, while increasing COL2. Mechanistically, Emapunil downregulated CD14/LY96 mRNA via TSPO, inhibiting NF-κB/TLR signaling and M1 polarization. TSPO inhibition abolished Emapunil' s regulatory effects on CD14/TLR4/LY96 pathways.CONCLUSIONTSPO plays an important role in OA occurrence and development. Emapunil targeting TSPO improves OA by modulating macrophage polarization and inflammation through the CD14/TLR4/LY96 pathway.","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"44 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335340","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}