Arthritis Research & Therapy最新文献

{"title":"Prospective analysis of B cell subset dynamics following telitacicept treatment in systemic lupus erythematosus","authors":"Xiaowei Chen, Lingzhen Hu, Lingxiao Zhu, Jianxin Tu, Jiajun Gui, Mengyuan Fang, Li Sun","doi":"10.1186/s13075-025-03584-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03584-x","url":null,"abstract":"Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease marked by B cell activation and autoantibody formation. Telitacicept, a dual inhibitor of the B cell pathway, neutralizes signals from B lymphocyte stimulator and a proliferation-inducing ligand. The aim of this study is to investigate the changes in detailed B cell subsets in SLE patients following Telitacicept treatment. Twenty active SLE patients (SLEDAI-2 K ≥ 6) were enrolled, with B cell subsets analyses and clinical assessments conducted at 0, 4, 12, and 24 weeks after initiating Telitacicept treatment. Additionally, B cell subsets were measured in 21 healthy controls. Flow cytometry was used to quantify B cell subsets. After six months of treatment, a 95% (19/20) SRI-4 response rate and a 35% (7/20) achievement of LLDAS were recorded. Compared to baseline, there were significant reductions in SLEDAI-2 K scores and anti-dsDNA levels (both p < 0.001), along with increases in complement C3 and C4 levels (both p < 0.001). Additionally, there was a significant decrease in 24-h urine protein levels (p = 0.004). B cell subset analysis revealed decreases in total B cells (p < 0.05), transitional B cells, naive B cells, and short-lived plasma cells (all p < 0.01). The proportion of B regulatory (Breg) cell increased (p < 0.05). Combining telitacicept with standard therapy induced significant changes in B cell subsets and clinical markers in SLE patients. The reduction in naive and transitional B cells, along with the restoration of Breg cell, suggests a potential positive influence on immunoregulatory capacity. Chineses Clinical Trials Registry; https://www.chictr.org.cn ; ChiCTR2400086874.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"6 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311924","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":"Enhanced cytotoxicity of aging associated NKG2C + CD8 + T cells in ankylosing spondylitis via HLA-B27","authors":"Kunhai Tang, Xiaobei Ma, Jian Gao, Lilu Zu, Yanyun Ma, Dachun Zhuo, Chenyuan Wu, Yulong Tang, Feng Qian, Li Jin, Jiucun Wang, Qi Zhu, Jing Liu","doi":"10.1186/s13075-025-03585-w","DOIUrl":"https://doi.org/10.1186/s13075-025-03585-w","url":null,"abstract":"This study aims to explore the common mechanisms between aging and the pathogenesis of ankylosing spondylitis (AS) and to identify potential therapeutic targets. A total of 87 patients with AS and matched controls were analyzed via multidimensional flow cytometry to examine the peripheral blood immune signature. Single-cell RNA sequencing was employed to characterize T-cell subsets. The infiltration of Ly49h + cells (the murine homolog of NKG2C) was observed in a collagen-induced arthritis mouse model, and functional experiments were conducted to validate the cytotoxicity of NKG2C + CD8 + T cells. The mechanisms were further confirmed via the use of HLA-B27 transgenic mice and RNA-sequencing. The peripheral blood immune signature of AS patients exhibited dysregulation similar to that observed during aging. NKG2C + CD8 + T cells activated the PI3K‒Akt signaling pathway and increased phagocytosis in AS patients. HLA-B27 stimulation significantly increased the cytotoxicity of this subset, an effect that could be reversed by NKG2C blockade. In HLA-B27 transgenic mice, Ly49h + T cells exhibited significantly enhanced degranulation ability. RNA sequencing validated the activation of the PI3K‒Akt pathway in NKG2C + CD8 + T cells by HLA-B27. HLA-B27 drives the cytotoxicity of aging-related NKG2C + CD8 + T cells via activation of the PI3K‒Akt signaling pathway. Targeting NKG2C inhibition may represent a novel therapeutic strategy for AS. This study elucidates the association between immune aging and the pathogenesis of AS, providing theoretical evidence for clinical intervention.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"26 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288472","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":"Association between rapid and sustained remission and clinician- and patient-reported outcomes in patients with rheumatoid arthritis: post hoc analysis of data from the SELECT-COMPARE study","authors":"Laure Gossec, Jayesh Patel, Aditi Kadakia, Siran Fang, Yi Peng, Sander Strengholt, Peter C. Taylor, Andrew Östör","doi":"10.1186/s13075-025-03580-1","DOIUrl":"https://doi.org/10.1186/s13075-025-03580-1","url":null,"abstract":"Rapid remission has been shown to be beneficial in patients with early rheumatoid arthritis (RA). This study assessed the association of rapid and sustained remission with long-term clinician- and patient-reported outcomes (CRO/PROs) in patients treated with b/tsDMARDs. This post hoc analysis used pooled data on patients with moderately-to-severely active RA receiving upadacitinib or adalimumab from the SELECT-COMPARE trial (NCT02629159) and its open-label long-term extension (up to 5 years). This study assessed the effect of achieving rapid remission, time to remission, and time in sustained remission on CRO/PROs. Rapid remission was defined as a Disease Activity Score 28 with C-reactive protein (DAS28-CRP) < 2.6 after 12 weeks’ treatment. The outcomes of interest included a variety of PROs, such as pain, fatigue, quality of life, and CROs (28 swollen/tender joint counts). Where available, outcomes were assessed for up to 5 years; mean change in outcomes, as well as adjusted odds ratios (aOR) of achieving minimal clinically important differences (MCIDs) or normative values. Multivariate regression analyses were conducted adjusting for baseline covariates. In total, 28% of patients (n/N = 247/865; mean disease duration: 8.2 ± 7.8 years) achieved rapid remission. Rapid remission was associated with significantly greater improvements from baseline in all outcomes at Week 26 and significantly greater odds of achieving MCIDs (aOR range: 2.2–5.6) or normative values (aOR range: 1.6–9.8) in most PROs, including pain, fatigue, and physical functioning, over the variable 5-year follow-up; significantly lower swollen/tender joint counts were also observed. Time to achieve remission was associated with better outcomes: for every month delay in achieving remission, likelihood of achieving MCIDs or normative values decreased, on average, by 13%. Increasing time spent in sustained remission was associated with long-term improvement in CRO/PROs. Remission is a key outcome in RA; this study showed that achieving rapid remission, as well as reducing time to achieving remission, was associated with less pain and fatigue, and better physical functioning and quality of life over 5 years. Similarly, increasing time spent in sustained remission correlated with sustained improvement in CRO/PROs. Striving for rapid, sustained remission leads to long-term benefits.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"151 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278474","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":"Granulocyte-macrophage colony-stimulating factor may contribute to spondyloarthritis development in HLA-B27 transgenic rat by affecting conventional dendritic cells function","authors":"Amel Ait Ali Said, Chiara Rizzo, Hendrick Mambu Mambueni, Félicie Costantino, Maxime Breban, Simon Glatigny","doi":"10.1186/s13075-025-03586-9","DOIUrl":"https://doi.org/10.1186/s13075-025-03586-9","url":null,"abstract":"Spondyloarthritis (SpA) is a chronic inflammatory disorder with axial and peripheral manifestations. A strong association between HLA-B27 and SpA has been known for more than 50 years. Remarkably, HLA-B27 and human β2-microglubulin transgenic rats (B27 rat) develop manifestations recapitulating SpA, referred to as rat SpA. Antigen-presenting cells such as dendritic cells (DC) and CD4 T cells are mandatory to develop rat SpA. Serum levels of granulocyte macrophage-colony stimulating factor (GM-CSF), a key growth factor for DC generation and functions, are significantly increased during SpA. Conventional (c)DCs can be divided in two subsets implicated either in immune tolerance (cDC1) or in adaptive immune responses induction (cDC2). In this study, we aimed to determine the influence of GM-CSF on cDC subsets functions linked to T cell activation and differentiation, in the B27 rat model. cDC subsets were isolated from spleens of B27 and nontransgenic (NTG) rats, primed with GM-CSF and tested for their ability to support CD4h T cell differentiation. RNA sequencing was performed on GM-CSF-primed cDC subsets. GM-CSF-primed cDC2 from B27 rat were strong inducers of TNF-producing proinflammatory CD4+ T cells. In contrast, whereas control cDC1 required GM-CSF to support T cell proliferation, HLA-B27+ cDC1 primed with GM-CSF failed to do so. RNA sequencing analysis demonstrated that HLA-B27 expression promoted endoplasmic reticulum stress and unfolded protein response in both cDC subsets. In addition, HLA-B27 expression promoted inflammatory cytokine synthesis by cDC2 and a signature interfering with regulation of cell adhesion and activation in cDC1. Altogether, our study reveals a dual role of GM-CSF during SpA. In one hand, GM-CSF promotes proinflammatory functions of cDC2. On the other hand, GM-CSF is required for cDC1 to induce T cell proliferation, and those functions are blunted by HLA-B27 expression.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"12 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278412","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":"Four months of treatment with anakinra combined with glucocorticoids for giant cell arteritis: a multicenter, randomized, double-blind, placebo-controlled trial","authors":"Hubert de Boysson, Kim Heang Ly, Loïk Geffray, Thomas Quemeneur, Eric Liozon, Holy Bezanahary, Noémie Le Gouellec, Alexandra Audemard, Anael Dumont, Samuel Deshayes, Jonathan Boutemy, Gwénola Maigné, Nicolas Martin Silva, Audrey Sultan, Brigitte Le Mauff, Gauthier Petit, Jean-Jacques Parienti, Achille Aouba","doi":"10.1186/s13075-025-03493-z","DOIUrl":"https://doi.org/10.1186/s13075-025-03493-z","url":null,"abstract":"Efficacy and tolerance of anakinra (ANK) in the treatment of giant cell arteritis (GCA) need to be assessed. This phase 3 study (NCT02902731) was a prospective multicenter, randomized, double-blind, placebo-controlled trial conducted over a 52-week period. GCA patients were randomized 1:1. From inclusion to week 16 (W16), patients in the anakinra (ANK) group received a daily subcutaneous injection of 100 mg of anakinra, whereas patients in the other group received placebo (PBO). In both arms, glucocorticoid (GC) discontinuation was planned at week 52 (W52). The endpoints were the relapse rates at W16, W26, and W52 and the completion of GC tapering. Given the emergence of the SARS-CoV-2 pandemic, the study was stopped prematurely. Thirty patients with new GCA diagnoses from 5 centers were randomized as follows: 17 in the ANK group and 13 in the PBO group. During the first 16 weeks, the relapse rates were 12% (n = 2) and 23% (n = 3) in the ANK and PBO groups, respectively (p = 0.63). At week 26, 12 (40%) patients had relapsed: 8 (47%) in the ANK group and 4 (31%) in the PBO group (p = 0.47). At W52, the relapse rate (overall, 50%) did not differ between the ANK group (53%; 9/17 patients) and the PBO group (46%; 6/13 patients) (p = 1). Two patients in each group discontinued GCs (p = 0.87). Seven serious AEs were reported in five patients, including 4 in patients receiving ANK. Although prematurely discontinued, this study does not support the use of 4 months of treatment with anakinra combined with GCs to reduce the risk of relapse or GC exposure. ClinicalTrials.gov NCT02902731.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"36 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237006","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":"Artificial intelligence-based Raynaud’s quantification index (ARTIX): an objective mobile-based tool for patient-centered assessment of Raynaud’s phenomenon","authors":"Marco Di Battista, Seda Colak, Anna Howard, Francesca Donadoni, Chris Owen-Smith, Andrea Rindone, Stefano Di Donato, Collette Hartley, Lesley-Anne Bissell, Francesco Del Galdo","doi":"10.1186/s13075-025-03569-w","DOIUrl":"https://doi.org/10.1186/s13075-025-03569-w","url":null,"abstract":"We aimed to develop an artificial intelligence algorithm able to assess Raynaud’s phenomenon (RP) from mobile phone photography, ensuring as a patient-centered, image-based method for RP quantification. ARTIX (artificial intelligence-based Raynaud’s quantification index) score was developed as a multi-step process of segmentation, decomposition and filters application to mobile phone pictures of the hand. ARTIX was validated by the ability to assess finger response to standardised cold challenge in patients with primary and secondary RP and healthy controls (HC) and compared with thermography as a reference. Forty-five RP patients (91.1% female, mean age 52.2 years, 75.5% secondary RP) were enrolled, along with 22 HC comparable for age and gender. RP patients presented significantly lower ARTIX values than HC both at baseline (p < 0.001) and across all timepoints of the cold challenge (p < 0.01 for all), paralleling a similarly significant difference observed by thermography. ARTIX score was higher in males and in patients taking vasoactive drugs, whereas lower values were obtained in patients with late capillaroscopic pattern, diffuse cutaneous skin subset, or negative for anti-centromere antibodies. ARTIX showed also good ability to discriminate between RP and HC response to cold challenge. We developed and validated ARTIX, a novel machine learning-driven method for the objective quantification of RP. Real-life longitudinal studies in patients with RP will determine the value of ARTIX to complement patient self-assessment surrogate measures of RP activity and severity.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"9 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201866","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":"Associations between the meniscal lesion parameters and knee joint structures and symptoms in patients with symptomatic knee osteoarthritis","authors":"Kaida Bo, Xin Liu, Yuanyi Zhang, Jianliang Ou, Xu Wang, Maolin Yang, Lianhui Zhao, Zhangwei Wu, Jingfeng Liu, Shuo Yang, Wei Zhang, Lelei Zhang, Zhonglin Xu, Kun Cao, Jun Chang","doi":"10.1186/s13075-025-03583-y","DOIUrl":"https://doi.org/10.1186/s13075-025-03583-y","url":null,"abstract":"To investigate cross-sectional associations between meniscal lesion parameters and knee joint structures and symptoms in patients with symptomatic knee osteoarthritis (KOA). A total of 102 subjects with symptomatic KOA were included in this study. Coronal magnetic resonance imaging was used to measure the meniscal parameters including the mean distance from medial to lateral meniscal lesions (Mean(MLD)), the mean value of tibial plateau width (Mean(TPW)) and the mean of the relative percentage of the medial to lateral meniscal lesions distance (Mean(RMLD)). The knee structural abnormalities and symptoms included Kellgren-Lawrence grade (KLG), cartilage volume, cartilage defects, bone marrow lesions (BMLs), joint space narrowing (JSN), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), pain, stiffness and physical dysfunction. In multivariate analyses, Mean(MLD) and Mean(RMLD) were significantly associated with KLG and were more efficient than cartilage volume and WOMAC in indicating the presence of KOA. The Mean(MLD) was significantly and negatively associated with total cartilage volume [β, 95%CI: -0.008(-0.012, -0.003)], medial tibial joint (MT) cartilage volume [β, 95%CI: -0.012(-0.017, -0.007)] and lateral tibial (LT) cartilage volume [β, 95%CI: -0.006(-0.011, -0.001)], and had positively associations with lateral tibiofemoral joint (LTFJ) cartilage defects, medial tibiofemoral joint (MTFJ) cartilage defects, LTFJ BMLs, and MTFJ BMLs [ORs, 95%CI: 1.063–1.116(1.007–1.059 to 1.119–1.177)] in patients with symptomatic KOA. There were positively associations between Mean(MLD) and WOMAC score [β, 95%CI: 2.145(1.160, 3.131)] in patients with KOA. Furthermore, The Mean(RMLD) was significantly and negatively associated with total cartilage volume [β, 95%CI: -0.005(-0.008, -0.002)], MT cartilage volume [β, 95%CI: -0.008(-0.011, -0.004)] and LT cartilage volume [β, 95%CI: -0.005(-0.008, -0.001)] and had significantly and positively associations with LTFJ cartilage defects, MTFJ cartilage defects, LTFJ BMLs, and MTFJ BMLs [ORs, 95%CI: 1.046–1.086(1.008–1.044 to 1.082–1.123)] in patients with symptomatic KOA. There were positively associations between Mean(RMLD) and WOMAC score [β, 95%CI: 1.465(0.793, 2.136)] in patients with KOA. Meniscus lesion parameter values were associated with changes in knee structures and increases in knee symptoms, suggesting that meniscal lesions may contribute to symptoms and structural abnormalities in the knee and increase the risk of KOA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"169 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201898","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":"Serum IL-40 is elevated in systemic sclerosis and is linked to disease activity, gastrointestinal involvement, immune regulation and fibrotic processes","authors":"Adéla Navrátilová, Sabína Oreská, Hana Wünsch, Klára Mocová, Ondřej Kodet, Marian Rybar, Glenda Alquicer, Aneta Prokopcová, Viktor Bečvář, Radim Bečvář, Aneta Jiránková, Anna Bobrová, Kateřina Bobrová, Karel Pavelka, Jiří Vencovský, Ladislav Šenolt, Lucie Andrés Cerezo, Michal Tomčík","doi":"10.1186/s13075-025-03570-3","DOIUrl":"https://doi.org/10.1186/s13075-025-03570-3","url":null,"abstract":"Interleukin 40 (IL-40) is a cytokine implicated in malignancies and rheumatic disorders. Its association with fibrotic mediators has been previously described. Since inflammation and fibrosis are hallmarks of systemic sclerosis (SSc), we aimed to analyze the role of IL-40 in SSc. IL-40 levels were analyzed in the serum of 90 SSc patients and 75 healthy controls (HCs). IL-40 expression in dermal biopsies from 5 SSc patients and 5 HCs was assessed via immunohistochemistry. IL-40 was analyzed in 39 SSc patients with interstitial lung disease treated with cyclophosphamide (CPA) and in 24 SSc patients with active progressive disease treated with rituximab (RTX). SSc activity was assessed by the European Scleroderma Study Group (ESSG) index. The effect of recombinant IL-40 on peripheral blood mononuclear cells (PBMCs) from 10 SSc patients was determined in vitro. IL-40 was analyzed in 24 individuals at risk of developing SSc (VEDOSS), who were categorized as progressors (n = 11) and nonprogressors (n = 13). IL-40 expression was elevated in the skin of SSc patients compared to HCs, particularly in fibroblasts and immune infiltrates. Serum IL-40 was increased in SSc compared to HCs (p < 0.0001) and was associated with ESSG (r = 0.372, p = 0.0005) and gastrointestinal involvement (p < 0.05). IL-40 correlated with serum IL-8 (r = 0.270, p = 0.019) and TGF-β1 (r = 0.301, p = 0.024) levels. In the CPA and RTX cohort, no significant changes in the serum IL-40 were observed upon treatment. Baseline and changes in IL-40 levels were associated with changes in several clinical parameters. IL-40 was elevated in patients at risk of SSc compared to HCs (p = 0.0003). No significant changes were observed in progressors vs. nonprogressors; however, IL-40 was associated with capillaroscopy findings (p < 0.05). IL-40 induced the upregulation of IL-6 (p = 0.002), MCP-1 (p = 0.002) and IL-10 (p = 0.002) in PBMCs from SSc patients in vitro. IL-40 was upregulated in the skin and serum of SSc patients and was associated with disease activity, gastrointestinal involvement and fibrotic mediators. Our in vitro findings indicate that IL-40 might be involved in the immune response and fibrotic processes in SSc.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144193284","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":"Roles of VWA1 and Rac2 in compensatory and decompensatory responses via FGF9/FGFR3 and p38 MAPK signaling pathways in condylar chondrocytes under distinct mechanical stress","authors":"Yuqi Liu, Fangwen Jia, Kangya Li, Chao Liang, Yanxi Li, Wei Geng","doi":"10.1186/s13075-025-03579-8","DOIUrl":"https://doi.org/10.1186/s13075-025-03579-8","url":null,"abstract":"Few studies paid attention to compensatory and decompensatory responses of condylar cartilage under different mechanical conditions and the underlying mechanism. Compensatory and decompensatory models were established. In vivo compensatory (0.5 mm occlusal elevation) and decompensatory (1.5 mm elevation) models were established in rats using zirconia occlusal plates. Parallel in vitro models subjected condylar chondrocytes to physiological (6%) or pathological (18%) cyclic tensile strain (CTS). Pivotal candidates that mediate the states of compensation and decompensation were screened through proteomic analysis, and validated through qRT-PCR, Western blot analyses, immunohistochemistry, and Alcian blue staining. Compensatory phenotypes dominated in 0.5 mm iOVD and 6% CTS groups, characterized by upregulated VWA1 expression and FGF9/FGFR3 pathway activation. Conversely, decompensation markers prevailed in 1.5 mm iOVD and 18% CTS groups, showing Rac2 elevation and p38 MAPK pathway induction. Further validation revealed that Vwa1 silencing attenuated compensatory responses under 6% CTS, while exogenous FGF9 restored them. Conversely, Vwa1 overexpression mitigated decompensation under 18% CTS, an effect nullified by FGFR3 inhibition. Rac2 knockdown reduced decompensatory responses to 18% CTS, whereas p38 MAPK activation reinstated these effects. Rac2 overexpression exacerbated decompensation under 6% CTS, reversible via p38 MAPK inhibition. VWA1 can modulate compensatory responses in condylar cartilage via regulating FGF9/FGFR3 signaling pathway, while Rac2 can mediate decompensatory responses via the modulation of p38 MAPK signaling pathway, which provide prospects for developing precise diagnostic and therapeutic strategies for temporomandibular joint osteoarthritis (TMJOA). Not applicable.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"184 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184177","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 development from peripheral blood monocytes is reduced in patients with radiographic axial spondyloarthritis on biological therapy","authors":"Cecilia Engdahl, Malin C. Erlandsson, Magnus Hallström, Anna Deminger, Helena Forsblad-d’Elia","doi":"10.1186/s13075-025-03578-9","DOIUrl":"https://doi.org/10.1186/s13075-025-03578-9","url":null,"abstract":"Radiographic axial spondyloarthritis (r-axSpA) is a chronic inflammatory disease that primarily affects the axial skeleton and entheses, leading to pathological spinal bone formation and systemic bone loss. Treatments with tumor necrosis factor inhibitors (TNFi) and interleukin-17 inhibitors (IL-17i) have shown efficacy in reducing inflammation and potentially impacting bone remodeling in r-axSpA. Osteoclasts, crucial for bone resorption, are derived from the monocytic cell lineage and regulated by proinflammatory cytokines. This study aimed to evaluate the osteoclast development capacity from peripheral blood monocytes in patients with r-axSpA with different treatment strategies and compare it to controls. This study included 28 patients with long-standing r-axSpA receiving various treatments, including disease-modifying anti-rheumatic drugs (DMARDs) and NSAIDs, as well as 16 blood-donor controls. Disease activity was assessed using the Ankylosing Spondylitis Disease Activity Score (ASDAS). CD14 + monocytes were isolated from blood samples and differentiated into osteoclasts in vitro by stimulation with three different conditions: (I) macrophage colony-stimulating factor (M-CSF), (II) M-CSF and receptor activator of nuclear factor-κβ (RANKL), and (III) M-CSF, RANKL, and tumor necrosis factor-alpha (TNF). Osteoclast and osteoclast precursor formation were assessed using tartrate-resistant acid phosphatase (TRAP) staining, and TRAP5b concentration in supernatants was measured by ELISA. The frequency of CD14 + monocytes was similar in patients with r-axSpA and controls, but the capacity to develop osteoclasts and osteoclast precursors was significantly decreased in the r-axSpA patients. Stratification of the patients based on treatment with or without biological DMARDs (bDMARDs) revealed no significant differences in ASDAS or frequency of CD14 + monocytes. Notably, only r-axSpA patients receiving bDMARDs exhibited a reduced ability to develop osteoclasts and osteoclast precursors compared to those not on bDMARDs and controls. Lower Trap5b concentrations in supernatants corroborated these findings. Our study demonstrates that patients with r-axSpA exhibit a reduced capacity for osteoclast formation from CD14 + monocytes isolated from peripheral blood. The process was modulated by treatment with bDMARDs, which might explain the previously shown sparing effect of bDMARDs on bone mineral density in r-axSpA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"30 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176622","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}