Arthritis & Rheumatology最新文献

{"title":"Deficiency of cartilage-specific Y-box binding protein 1 represses NF-κB signaling and alleviates osteoarthritis progression.","authors":"Xinyu Li,Zhao Zhang,Jinwei Xie,Weihua Guo,Zhenhan Deng,Zeyu Huang","doi":"10.1002/art.43311","DOIUrl":"https://doi.org/10.1002/art.43311","url":null,"abstract":"OBJECTIVETo explore the role of Y-box binding protein 1 (YBX1) in the pathogenesis of osteoarthritis (OA).METHODSThe proteome and phosphoproteome were compared between the intact and osteoarthritic regions of the cartilage from patients undergoing total knee arthroplasty, establishing a connection between the pathology and YBX1 upregulation. Normal C57BL/6 and cartilage-specific Ybx1-deficient mice underwent medial meniscal destabilization surgery; the behavior, micro-computed tomography, and histology were compared. YBX1 was overexpressed in the C28/I2 cell line, and potential binding partners were identified using immunoprecipitation and mass spectrometry. MedChemExpress drug libraries were screened for potential small-molecule inhibitors of YBX1, and candidates were injected intra-articularly into a mouse OA model.RESULTSThe total YBX1 and YBX1 phosphorylated levels at S102 were higher in the osteoarthritic than intact human cartilage. Ybx1 knockout in chondrocytes alleviated disease progression in an OA mouse model. Upregulation of YBX1 in chondrocytes activated NF-κB signaling. Phosphorylation of YBX1 at S102 promoted its entry into the nucleus, where it inhibited NF-κB-repressing factor (NKRF), upregulating target genes of NF-κB. Virtual drug screening identified hesperidin methychalcone and mulberroside A as candidates for inhibiting S102 phosphorylation, alleviating disease progression in an injury-induced OA mouse model.CONCLUSIONYBX1 contributes to OA progression by inhibiting NKRF, activating NF-κB signaling; therefore targeting YBX1 is a potential therapeutic strategy for the treatment of OA.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"9 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rheumatoid arthritis: femoral heads gone with the decade.","authors":"Ting Zhang,Jing Xue","doi":"10.1002/art.43294","DOIUrl":"https://doi.org/10.1002/art.43294","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"23 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Some More Equal Than Others: The Divergence of Cardiac Risk in the Use of NSAIDs Versus Colchicine for Treating and Preventing Gout.","authors":"Michael H Pillinger,Michael Toprover","doi":"10.1002/art.43324","DOIUrl":"https://doi.org/10.1002/art.43324","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"14 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C3a-C3aR1-mediated interactions between fibroblast-like synoviocytes and macrophages promote the progression of rheumatoid arthritis.","authors":"Minglong Cai,Zhenyu Li,Xi Wen,Huizhi Jin,Yujing Li,Haibo Wu,Chao Yang,Zhu Chen","doi":"10.1002/art.43319","DOIUrl":"https://doi.org/10.1002/art.43319","url":null,"abstract":"The inflammatory microenvironment in rheumatoid arthritis (RA) synovium is highly complex, comprising functional units known as cellular neighborhoods (CNs). However, how cell interactions within CNs shape the inflammatory microenvironment in RA remains unclear. Here, we utilized imaging mass cytometry (IMC) and single-cell RNA sequencing to dissect the CNs within RA synovium, uncovering critical cell-cell interactions and evaluating whether disrupting interaction signals could alleviate disease severity in collagen-induced arthritis (CIA) mouse model. Our findings revealed that CNs enriched with fibroblast-like synoviocytes (FLS) and immune cells, particularly FLS and macrophages, were more frequent in RA synovium compared to osteoarthritis (OA). Further single-cell RNA sequencing analysis showed that FLS specifically upregulated complement C3 while macrophages displayed high level of C3 receptor, C3aR1. Interestingly, C3a derived from FLS enhanced type I interferon response in macrophages, and blockade of the C3a-C3aR1 signaling reduced secretion of IFN-β in macrophages, thereby affecting FLS activation. Additionally, inhibition of C3a-C3aR1 signaling attenuated the severity of CIA mice with decreased immune cell infiltration, reduced FLS activation, and less bone destruction. Our study suggests that FLS promotes synovial inflammation via interaction with macrophages through a C3a-C3aR1 signaling-mediated positive feedback regulation. Thus, targeting C3a-C3aR1 signaling might provide a new therapeutic strategy for RA.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"93 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Familial Aggregation in Psoriatic Arthritis: Phenotypic Differences in Patients with and without a Family History of Psoriatic Disease","authors":"Catherine Howe, Jiyuan Hu, Weixi Chen, Kyra Chen, Adamary Felipe, Stephanie Eichman, Margaret Coyle, Eileen Lydon, Andrea L. Neimann, Soumya Reddy, Jose U. Scher, Rebecca H. Haberman","doi":"10.1002/art.43325","DOIUrl":"https://doi.org/10.1002/art.43325","url":null,"abstract":"ObjectivesWhile up to 45% of patients with psoriatic arthritis (PsA) have a family history of psoriatic disease, it is unclear whether this family history contributes to a distinct PsA phenotype and/or timing of disease onset. We aimed to identify differences in onset, domain involvement, and disease activity based on family history of psoriatic disease.Methods843 PsA patients were enrolled in an observational, longitudinal registry. Demographics, medical history, family history, and psoriatic phenotype and activity were collected.Results379 patients (45.0%) had at least one first‐degree (FDR) or second‐degree relative (SDR) with psoriatic disease. Those with a family history developed psoriasis and PsA earlier than those with no family history (27.6 vs. 32.2 years, p < 0.01; 37.6 vs. 40.3, p < 0.01) and were more likely to have entheseal involvement (36.7% vs. 30.0%, p < 0.05). Patients with an FDR/SDR with PsA were diagnosed with psoriasis and PsA earlier than those with an FDR/SDR with psoriasis alone, followed by those with no family history (26.3 vs. 27.8 vs. 32.2 years, p < 0.01; 36.5 vs. 37.9 vs. 40.3 years, p = 0.01).ConclusionIn this cohort, PsA patients with a family history of psoriatic disease were diagnosed with psoriasis and PsA earlier, and were more likely to have entheseal involvement, compared to those without a family history. Further research incorporating molecular and immune features is needed to investigate genetic, environmental and epigenetic factors that impact PsA phenotype and severity, as well as the transition from psoriasis to PsA.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"12 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of B Cell Tolerance in Health and Autoimmunity.","authors":"Sivasankaran Munusamy Ponnan,Shaun W Jackson","doi":"10.1002/art.43316","DOIUrl":"https://doi.org/10.1002/art.43316","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"27 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregnancy outcomes in women with systemic sclerosis before and/or after diagnosis, and by parity - A Swedish population-based cohort study.","authors":"Weng Ian Che,Luigi Annicchiarico,Laura Andreoli,Olof Stephansson,Marie Holmqvist,Karin Hellgren","doi":"10.1002/art.43312","DOIUrl":"https://doi.org/10.1002/art.43312","url":null,"abstract":"OBJECTIVETo assess risks of adverse pregnancy outcomes (APO) in a contemporary cohort of women with systemic sclerosis (SSc) in relation to the timing of SSc diagnosis and by parity.METHODSFrom the nationwide Swedish Medical Birth Register, we assembled pregnancies with births in women with SSc and in comparator women from the general population 1998-2021. We classified pregnancies according to the timing of SSc diagnosis at birth: post-SSc; after SSc diagnosis (n=94), and pre-SSc; 0-3 years (n=39) or >3 years (n=839) before diagnosis of SSc. We used regression models estimating relative risks (RR) of APO in post-SSc, and odds ratios (OR) in pre-SSc pregnancies with 95% confidence interval (CI), respectively.RESULTSFor post-SSc pregnancies, RR of preeclampsia (3.8; 1.8-7.8), preterm birth (3.3; 1.8-6.1), and caesarean delivery (2.5; 1.8-3.5) were increased. By contrast, there were no indications of increased proportions of maternal or neonatal death, nor stillbirth. Stratifying on parity, risks were considerably higher among primiparous post-SSc women; RR of preeclampsia (7.5; 3.5-16.1) and of preterm birth (5.1; 2.5-10.5). We also noted increased odds of APO in pre-SSc pregnancies, with the highest estimates in the 0-3 years pre-SSc pregnancies.CONCLUSIONContemporary women with SSc displayed markedly increased risks of several APO after SSc diagnosis; the risk of some APO was already increased before diagnosis, particularly within 3 years. Our findings suggest that both preclinical and overt SSc have a substantial impact on pregnancy outcomes, especially in the first pregnancy, highlighting the importance of specialized care and close monitoring.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"33 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Correspondence to Efficacy of a Tumor necrosis Factor Inhibitor in Chronic Low-Back Pain with Modic type 1 Changes: A Randomized Controlled Trial.","authors":"Elisabeth Gjefsen,Lars C Bråten,Ansgar Espeland,Guro L Goll,Kjersti Storheim,John A Zwart","doi":"10.1002/art.43309","DOIUrl":"https://doi.org/10.1002/art.43309","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"51 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monocyte-derived macrophages-synovial fibroblasts crosstalk unravels oncostatin signaling network as a driver of synovitis in osteoarthritis.","authors":"Damien Laouteouet,Olivier Bortolotti,Léa Marineche,Nicole Hannemann,Manon Chambon,Yaël Glasson,Anne-Sophie Dumé,Julien De Lima,Maud Fournial,Dylan Touchet,Dany Séverac,Felicia Leccia,Christophe Duperray,Henri-Alexandre Michaud,Farida Djouad,Benoît Le Goff,Frédéric Blanchard,Florence Apparailly,Gabriel Courties","doi":"10.1002/art.43299","DOIUrl":"https://doi.org/10.1002/art.43299","url":null,"abstract":"OBJECTIVEOsteoarthritis (OA) is a debilitating joint disease characterized by cartilage degradation, synovial inflammation, and pain. Macrophages have been implicated in OA pathology, but the origins and functions of diverse macrophage subsets seeding the synovial joint tissue remain incompletely understood. This study investigates macrophage heterogeneity, ontogeny, fate, and communication with stromal niche cells in OA.METHODSSingle-cell RNA sequencing was employed on synovial cells isolated from mice with collagenase-induced OA (CiOA) and CD14+ macrophages from four OA patients. We combined flow cytometry, genetic fate mapping, and imaging mass cytometry to profile synovial macrophage subsets. Cell-cell communication analyses were performed to investigate interactions cellular networks.RESULTSThree macrophage subsets with distinct gene signatures and origins were identified in CiOA, including contributions to synovial inflammation and tissue remodeling. Fate mapping via CCR2-creER and CX3CR1-creER mice revealed the expansion of monocyte-derived TIM4- MHCIIlow/high macrophages. Monocyte-independent TIM4+ CX3CR1+ macrophages operated a synovial niche shift, migrating near vascularized structures in the synovial sub-intima. Notably, the OSM/OSMR signaling network emerged as a critical pathway linking recruited CCR2-derived macrophages to fibroblast activation. In individuals with OA, single-cell transcriptomics identified a conserved MertKlow CD48high CCR2pos macrophage subpopulation as a key source of OSM.CONCLUSIONOur study provides insights into macrophage subsets and their interplay with the joint microenvironment, bridging the gap between their origins, transcriptomic profiles, and roles in OA. Specifically, the OSM/OSMR axis represents a pivotal mechanism in recruited macrophage-fibroblast crosstalk, offering potential targets for novel biomarkers and therapies to manage OA-related synovitis.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"2 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibodies targeting G protein-coupled receptors in systemic sclerosis. Comment on the article by van Oostveen WM et al.","authors":"Reza Akbarzadeh,Alexander Hackel,Jens Y Humrich,Kristina Kusche-Vihrog,Gabriela Riemekasten","doi":"10.1002/art.43300","DOIUrl":"https://doi.org/10.1002/art.43300","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}