Arthritis Research & Therapy最新文献

{"title":"Piezo1-centered mechanotransduction in knee osteoarthritis: multicompartment mechano-inflammatory networks and therapeutic opportunities","authors":"Jing Li,Bo Dong,Xueqin Zeng,Fei Gao,Baohui Wang","doi":"10.1186/s13075-026-03927-2","DOIUrl":"https://doi.org/10.1186/s13075-026-03927-2","url":null,"abstract":"Abstract Knee osteoarthritis (KOA) is increasingly recognized as a whole-joint mechano-inflammatory disorder in which abnormal loading, tissue remodeling, and inflammatory sensitization reinforce one another. Piezo1 is a context-dependent mechanotransduction hub that links mechanical cues to Ca 2+ -dependent inflammatory, catabolic, cell-death, and organelle-stress responses. This focused review, supported by a structured search of PubMed, Web of Science, and China National Knowledge Infrastructure from database inception through June 2, 2026, synthesizes evidence across articular cartilage, synovium, subchondral bone, osteophyte formation, and the pain-related microenvironment. Dysregulated Piezo1-associated signaling has been implicated in extracellular matrix degradation, chondrocyte dysfunction, cell-fate imbalance, and organelle stress. Importantly, Piezo1 is not uniformly pathogenic: excessive activation can aggravate injury in mature chondrocytes and other joint cells, whereas Piezo1 activity may support reparative responses in selected progenitor-cell populations. Preclinical studies have investigated whether traditional Chinese medicine-related interventions alter components of the Piezo1-associated mechano-inflammatory network, although direct target engagement and causal validation remain limited. Artemisinin, wogonin, Shengyu Decoction, and Gubi Zhitong Formula have been associated with changes in distinct molecular modules, whereas evidence linking acupuncture and acupotomy to Piezo1 remains limited to heterogeneous preclinical models and does not establish direct or Piezo1-specific therapeutic mechanisms. However, translation remains limited by heterogeneous models, insufficient compartment- and cell-specific validation, incomplete exposure and target-engagement data, and inconsistent procedural standards. Future studies should integrate local and reversible intervention strategies, rigorous quality control, standardized procedural and stimulation parameters, and cell-specific causal validation. Piezo1 may therefore serve as a stratifiable and testable organizing axis for developing more precise KOA interventions.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"141 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208669","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":"Methotrexate in early systemic sclerosis: skin outcomes and drug survival in real-life practice","authors":"Claudia Iannone,Ilaria Magi,Maria Rosa Pellico,Cristina Bochicchio,Antonina Minniti,Roberto Caporali,Nicoletta Del Papa","doi":"10.1186/s13075-026-03910-x","DOIUrl":"https://doi.org/10.1186/s13075-026-03910-x","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"40 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210498","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":"GLP-1 receptor agonists as novel renoprotective agents in lupus nephritis","authors":"Xinyu Zhao,Chen Liu,Yongchun Li,Junpeng You,Yuhui Gan,Huimiao Hu,Shuangshuang Li,Weijing Yong,Xiaoyang Wang,Xiaoxue Zhang,Yaling Zhai,Genyang Cheng,Xujie Zhou,Hongde Xu,Yuanyuan Qi","doi":"10.1186/s13075-026-03922-7","DOIUrl":"https://doi.org/10.1186/s13075-026-03922-7","url":null,"abstract":"Abstract Background Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus and a major cause of chronic kidney disease (CKD). Despite advances with immunosuppressive therapy, many patients continue to develop progressive renal impairment. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), approved for diabetes and CKD, have shown renoprotective effects, but their potential in LN remains undefined. Methods We evaluated the renoprotective effects of liraglutide in lupus-prone MRL/lpr mice using functional, histopathological, and molecular analyses integrated with single-nucleus transcriptomics. Mechanistic studies involved ferroptosis inhibition and pharmacological blockade of cAMP signaling. To provide clinical context, we also describe a patient with class III + V LN who initiated semaglutide during immunosuppressant tapering. Results In lupus-prone MRL/lpr mice, liraglutide reduced proteinuria, improved renal function, and ameliorated histopathological injury without altering systemic autoantibody levels. Single-nucleus transcriptomics revealed cell type–specific remodeling, including suppression of inflammatory and metabolic pathways in podocytes, mesangial, and tubular cells, alongside signatures of tubular repair. Liraglutide treatment was associated with reduced immune infiltration, NF-κB and NLRP3 signaling, fibrosis, oxidative stress, and ferroptosis-related changes, as well as enhanced autophagy. Ferroptosis inhibition recapitulated several protective effects of liraglutide, whereas cAMP blockade attenuated its effects on renal function, inflammation, oxidative stress, and ferroptosis-related parameters. In a single clinical observation, proteinuria decreased following semaglutide initiation during ongoing immunosuppressive management; however, no causal inference can be made from this case. Conclusions GLP-1RAs improved renal outcomes in lupus-prone mice in association with anti-inflammatory, antioxidant, and reduced ferroptosis-related changes. Pharmacological experiments further support the involvement of cAMP signaling and ferroptosis in these renoprotective effects.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208670","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":"Progression of sacroiliac joint structural lesions in axial spondyloarthritis: a longitudinal comparative study of MRI and radiography among European patients in routine clinical care","authors":"Annik Steimer,Raphael Micheroli,Claudia Lourenço Rodrigues,Jonas Brändli,Anna E. F. Hadsbjerg,Simon Krabbe,Nora Vladimirova,Iris Eshed,Torsten Diekhoff,Robert G. W. Lambert,Susanne J. Pedersen,Manouk de Hooge,Kristýna Bubová,Monika Gregová,Michael J. Nissen,Burkhard Möller,Jakub Závada,Ziga Snoj,Karlo Pintaric,Bjorn Gudbjornsson,Ziga Rotar,Iwona Sudol-Szopinska,Kasper Gosvig,Alexander Bernatschek,Maurice Donzallaz,Jakob M. Møller,Marie Wetterslev,Stephanie Wichuk,Merete Lund Hetland,Lykke M. Ørnbjerg,Mikkel Østergaard,Adrian Ciurea","doi":"10.1186/s13075-026-03921-8","DOIUrl":"https://doi.org/10.1186/s13075-026-03921-8","url":null,"abstract":"Abstract Background To compare the performances of magnetic resonance imaging (MRI) and radiography in detecting changes in structural lesions of the sacroiliac joints (SIJs) in routine care patients with axial spondyloarthritis (axSpA). Methods SIJ MRIs and radiographs of routine care patients with axSpA in four European countries were collected as part of the EuroSpA Imaging Project. Patients were included if both MRIs and radiographs (≤ 6 months apart) were available at two time points (≥ 1 year apart). Images were evaluated centrally and independently by two trained readers (blinded to chronology and other imaging), applying the Spondyloarthritis Research Consortium of Canada SIJ scores (MRI) and the modified New York criteria (mNY, radiography). Intermodality agreement was assessed cross-sectionally and for change. Results One-hundred-and-five patients (65 male, mean (SD) age 38.1 (10.9) years, symptom duration 9.1 (9.7) years), with a follow-up interval of 2.6 (1.4) years) were included. Baseline agreement between radiography and MRI was slight-to-fair for erosion detection (kappa = 0.12 to 0.42), poor to slight for sclerosis (− 0.04 to 0.07), and substantial to almost perfect for ankylosis (0.66–0.86). Agreement for change over time was poor-to-slight (− 0.04 to 0.20). While lesions remained largely stable on radiography (≤ 6 patients showing change in scores, per lesion type), MRI detected change in at least one lesion in ≥ 50% of patients (positive/negative change in scores (“progression”/”regression”): sclerosis 27/30, erosion 51/38, ankylosis 14/5). A composite MRI score of damage correlated well with mNY grades (Spearman rho = 0.65–0.69). Conclusions Compared to radiography, MRI detected more SIJ structural lesion changes over time, reflecting its ability to capture dynamic changes not readily visible on radiography.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"12 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210365","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":"Proteomic landscape of IGF-I gene transfer in osteoarthritis-derived human bone marrow stromal cells undergoing chondrogenesis","authors":"Patricia Quaranta,Jagadeesh K. Venkatesan,Valentina Calamia,Patricia Fernández-Puente,Selva Riva-Mendoza,Francisco J. Blanco,Magali Cucchiarini,Cristina Ruiz-Romero","doi":"10.1186/s13075-026-03919-2","DOIUrl":"https://doi.org/10.1186/s13075-026-03919-2","url":null,"abstract":"Abstract Background Osteoarthritis (OA) is a progressive joint disease marked by the breakdown of cartilage and impaired repair capacity. Gene therapy applied to human bone marrow-derived adherent stromal cells (BM-MSCs) with recombinant adeno-associated virus (rAAV) vectors represents a promising strategy for cartilage regeneration. However, the molecular mechanisms underlying its effects remain largely unexplored. In this study, we investigated the proteomic changes induced by rAAV-mediated insulin-like growth factor I (IGF-I) gene transfer during the chondrogenic differentiation of BM-MSCs derived from OA patients. Methods BM-MSCs from OA donors were transduced with recombinant rAAV vectors encoding either IGF-I or the lacZ gene (β-galactosidase) as a control and cultured in three-dimensional micromass systems under chondrogenic conditions for 21 days. Histological, immunohistochemical (IHC) and immunofluorescence (IF) analyses were performed to characterize the chondrogenic phenotype of the model and to provide orthogonal validation of selected proteomic findings. Mass spectrometry-based proteomic profiling identified protein detection patterns and quantitative changes associated with IGF-I overexpression. Pathway and protein-protein interaction (PPI) analyses were carried out to explore the functional implications of differentially expressed proteins. Results A total of 4,284 proteins were identified, of which 112 showed notable changes in detection patterns or abundance associated with IGF-I. Functional enrichment analyses showed involvement of pathways related to metabolism, endoplasmic reticulum (ER) homeostasis, apoptosis regulation, cell proliferation, glycosylation, and the endosomal sorting complex required for transport (ESCRT) machinery. Histological and IHC analyses provided supportive evidence of cartilage-related matrix deposition. Orthogonal validation by IHC and IF confirmed the IGF-I-mediated upregulation of β-catenin and exportin-1 (XPO1). Further analyses provided exploratory evidence of increased active β-catenin and predominantly extranuclear distribution of sirtuin-1, a known XPO1 substrate, in IGF-I-transduced micromasses. Conclusion This study provides the first proteomic characterization of rAAV-mediated IGF-I gene therapy in OA-derived BM-MSCs undergoing chondrogenesis. The IGF-I gene transfer was associated with broad proteomic changes involving metabolic and protein processing pathways, and enhanced cartilage-specific matrix deposition, highlighting molecular mechanisms of potential relevance to cartilage repair in OA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"42 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149150397","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":"Plasma metabolomics reveals candidate biomarkers associated with individual treatment response in psoriatic arthritis","authors":"Mieke L. M. Bentvelzen,Wei Yang,Yu Zhang,Alida Kindt,Amy C. Harms,Julia Spierings,Amin Herman,Shasti C. Mooij,Lydia G. Schipper,Harald E. Vonkeman,Simone A. Vreugdenhil,TOFA-PREDICT author group,Kavish J. Bhansing,Sandra T. A. van Bijnen,Radjesh J. Bisoendial,Lenny van Bon,Antoaneta C. Comarniceanu,Tim L. T. A. Jansen,Arno W. R. van Kuijk,Marc R. Kok,Emmerik F. A. Leijten,Z. Nazira Jahangier,Astrid M. van Tubergen,Siska Wijngaarden,Sylvana W. Kadir,Simon C. Mastbergen,Thomas Hankemeier,Paco M. J. Welsing","doi":"10.1186/s13075-026-03909-4","DOIUrl":"https://doi.org/10.1186/s13075-026-03909-4","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"89 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149150381","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":"Protein misfolding in the synovium: the hidden face of osteoarthritis progression?","authors":"Veronica Panichi,Silvia Costantini,Marta Columbaro,Carla Renata Arciola,Giuseppe Filardo,Alessandro Di Martino,Rosa Maria Borzì,Paolo Dolzani","doi":"10.1186/s13075-026-03918-3","DOIUrl":"https://doi.org/10.1186/s13075-026-03918-3","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"28 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149150382","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":"Advancing IL-1 inhibition for OA: Lessons learned from clinical trials and new approaches","authors":"Timothy L. Boyer,Helna M. Baby,Bill Hakim,Ambika G. Bajpayee","doi":"10.1186/s13075-026-03904-9","DOIUrl":"https://doi.org/10.1186/s13075-026-03904-9","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"10 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149150394","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":"Impact of the 2023 ACR/EULAR classification criteria on thrombotic antiphospholipid syndrome: reclassification patterns and long-term outcomes in a 419-patient cohort","authors":"Rafael Gálvez-Sánchez,Rodrigo Cantera Estefanía,María Oviedo Madrid,María Abando Casuso,Héctor Cruz,Raquel García Ruiz,Marina Herrero López,José Antonio Flores García,Irene Gorostidi Álvarez,Ariadna García Ascacibar,Ligia Gabriela Gabrie Rodríguez,Lucrecia Yáñez San Segundo,Marcos López Hoyos,Juan José Domínguez García,María Luisa González Ponte,Belén González Mesones,J. Luis Hernández Hernández,Víctor Manuel Martínez Taboada","doi":"10.1186/s13075-026-03916-5","DOIUrl":"https://doi.org/10.1186/s13075-026-03916-5","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"8 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089188","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":"Temporal dynamics of inflammatory proteins in the pre-symptomatic phase of rheumatoid arthritis related to seroconversion","authors":"Anton Ahlsved,Anders Lundquist,Kristina Lejon,Solbritt Rantapää-Dahlqvist,Mikael Brink","doi":"10.1186/s13075-026-03917-4","DOIUrl":"https://doi.org/10.1186/s13075-026-03917-4","url":null,"abstract":"Abstract Objective Autoimmune processes in rheumatoid arthritis (RA) begin years before clinical symptom onset. This study aimed to analyse inflammation-related proteins in individuals during the pre-symptomatic phase, in relation to healthy controls and patients with early RA, and their relationship to seroconversion. Methods Plasma samples collected prior to symptom onset from individuals who later developed RA ( n  = 419), healthy population controls ( n  = 49), and patients with early RA at diagnosis ( n  = 68) were obtained from a biobank. All samples were analysed for 92 inflammation-related proteins using a proximity extension assay and for anti-CCP2 antibodies and rheumatoid factor. After quality control 77 proteins remained. To identify differentially expressed proteins and enriched pathways, statistical analyses including logistic regression, generalized additive models, and network enrichment analysis was applied. Results Four proteins (MMP10, IL6, CCL19, and IL10RB) showed a higher concentration in pre-symptomatic individuals compared to controls ( p  < 0.05). Twelve proteins were associated with seropositivity in the pre-symptomatic phase and network enrichment analysis of these revealed associated pathways related to the complement system and cytokine activity. Three proteins (CXCL10, CCL7, and CDCP1) were consistently associated with seroconversion and showed increasing trends approaching symptom onset in individuals who seroconverted, but not in individuals who remained seronegative. Proteins associated with early seroconversion were associated with T-cell activity, whereas many of the proteins associated with late seroconversion were associated with bone remodelling, mineral metabolism, and collagen degradation. Conclusion Proteomic alterations are detectable years before RA onset and linked to autoantibody development. Seroconverters differ from those who remain seronegative even in the pre-symptomatic period, supporting the notion that seropositive and seronegative RA represent biologically distinct entities from the earliest stages of the pathogenesis.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089216","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}