Arthritis Research & Therapy最新文献

{"title":"Low-dose rituximab in lupus enteritis: a comparative study on its efficacy in modulating mucosal immunity and reducing inflammation","authors":"Ying Liu, YuJie Pang, Yang Liu, Na Zhang, LiangYu Mi, Yanan Gao, Wenqin Gao, Ke Xu","doi":"10.1186/s13075-025-03653-1","DOIUrl":"https://doi.org/10.1186/s13075-025-03653-1","url":null,"abstract":"Lupus enteritis (LE) is a serious manifestation of systemic lupus erythematosus (SLE), yet optimal treatment strategies remain unclear. This study aimed to compare the efficacy of rituximab (RTX) plus glucocorticoids versus glucocorticoids combined with conventional immunosuppressants in patients with moderate-to-severe LE. We retrospectively analyzed 36 patients with SLE-related intestinal involvement treated at our center between January 2015 and August 2024; sixteen received RTX plus glucocorticoids, and twenty received glucocorticoids with conventional immunosuppressants. Baseline characteristics, clinical features, abdominal CT findings, laboratory parameters (including serum and fecal IgA, IL-6, TNF-α, and IL-10), and disease activity scores (SLEDAI-2 K and BILAG-2004) were assessed. For fecal IgA analysis, age- and sex-matched healthy controls without relevant diseases or recent antibiotic/microbiota-modulating use were included. Treatment response and safety outcomes were compared over 6 months. Both patient groups exhibited comparable baseline characteristics. Both treatment strategies led to significant improvements in clinical symptoms and imaging abnormalities—including bowel wall thickening, mesenteric effusion, comb sign, or target sign—with no significant differences observed between the groups. After six months of treatment, the median SLEDAI-2 K score in the rituximab (RTX) group decreased from 15 to 0 (p < 0.001), and the BILAG-2004 score decreased from 31.5 to 0 (p < 0.001). IL-6 levels in the RTX group also significantly declined from 26.57 ± 7.94 pg/mL to 4.15 ± 2.10 pg/mL (p < 0.01), with a greater reduction compared to the control group. Fecal IgA levels were higher in lupus enteritis patients than in healthy controls and decreased in both groups following treatment. Baseline IL-6 correlated with SLEDAI-2 K and BILAG-2004 scores, whereas fecal IgA was elevated in patients with mesenteric effusion but not associated with overall disease activity. At 6 months, remission was achieved in 93.8% of RTX-treated patients and 85% of controls (p = 0.418), with comparable safety profiles. Both RTX plus glucocorticoids and conventional immunosuppressants plus glucocorticoids are effective in inducing clinical and radiologic remission in LE. RTX may lead to faster improvement in certain serologic and inflammatory biomarkers. Larger studies with longer follow-up and stratification by systemic involvement are warranted to optimize individualized treatment strategies.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"54 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188763","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":"Inflammation-mediated regional brain alterations associated with mild cognitive impairment in knee osteoarthritis","authors":"Chao Li, Congqiang Hao, Kechong Zhou, Peng Zhang, Quan Sun, Zhengxi Li","doi":"10.1186/s13075-025-03646-0","DOIUrl":"https://doi.org/10.1186/s13075-025-03646-0","url":null,"abstract":"Knee osteoarthritis (KOA), a degenerative joint disease marked by chronic pain, is associated with systemic inflammation that may extend to neurocognitive dysfunction. While chronic low-grade inflammation in KOA has been implicated in mild cognitive impairment (MCI), a prodromal stage of dementia, the mediating role of inflammation in brain functional reorganization remains unclear. This study integrated neuroimaging, inflammatory biomarkers, and machine learning to investigate inflammation-mediated brain functional alterations in 63 KOA patients with/without MCI. Serum levels of pro-inflammatory cytokines (IL-6, TNF-α) and resting-state fMRI data were analyzed using voxel-wise Regional Homogeneity (ReHo) and Amplitude of Low-Frequency Fluctuation (ALFF). Comparisons across healthy controls, KOA-MCI, and KOA-non-MCI groups identified MCI-linked functional alterations in the medial prefrontal cortex (mPFC), precuneus, and superior temporal gyrus. Mediation analysis revealed that mPFC ReHo significantly mediated the relationship between elevated IL-6 and cognitive decline. Machine learning models incorporating ReHo features from mPFC demonstrated robust classification of MCI status (AUC: 0.87), validated in an external dataset. Our findings suggest that IL-6-driven mPFC dysfunction is a potential pathway linking KOA-related inflammation to MCI, while highlighting the combined utility of ReHo/ALFF metrics in mPFC, precuneus, and temporal regions as potential neuroimaging biomarkers. This multimodal approach advances understanding of neuroinflammatory mechanisms in osteoarthritis and provides a framework for early detection of cognitive vulnerability in KOA populations.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"53 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141562","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 Glycolysis-HIF-1α axis induces IL-1β of macrophages in rheumatoid arthritis","authors":"Yimeng Jia, Rongli Li, Linfang Huang, Xunyao Wu, Lidan Zhao, Huaxia Yang, Xin You, Yunyun Fei","doi":"10.1186/s13075-025-03647-z","DOIUrl":"https://doi.org/10.1186/s13075-025-03647-z","url":null,"abstract":"Rheumatoid arthritis (RA) is an aggressive, systemic autoimmune disease in which overactivated macrophages play a critical role in its pathogenesis. This study aimed to explore the potential role of glycolytic reprogramming in the production of proinflammatory cytokines by macrophages in RA. The Seahorse assay was conducted on RA or healthy control (HC) serum-treated human monocyte-derived macrophages (HMDMs) to evaluate glycolysis levels. RNA sequencing was performed to identify activated signaling pathways and key molecules in HMDMs stimulated by RA serum. The proinflammatory cytokines and hypoxia-inducible factor 1α (HIF-1α) were verified by Western blotting and quantitative polymerase chain reaction (qPCR). We found that HMDMs stimulated with RA serum showed higher aerobic glycolysis levels than those treated with HC serum, along with higher expression of glycolysis-related genes, including hexokinase2 (HK2), pyruvate kinase L/R (PKLR), and phosphoglycerate kinase 1 (PGK1). Furthermore, RA serum-treated macrophages exhibited a higher level of interleukin-1 beta (IL-1β), and the expression of IL-1β positively correlated with HK2. Inhibition of glycolysis by 3-bromopyruvate (3BrPA) or HK2 knockdown significantly suppressed IL-1β production in macrophages. The HIF-1α-associated signaling pathways and HIF-1α protein levels were also elevated in RA serum-treated macrophages. Inhibition of glycolysis by 3BrPA or knockdown of HK2 reduced HIF-1α. Inhibiting HIF-1α can suppress IL-1β production of RA serum-treated macrophages, and vice versa. TNF-α and IL-1β enhanced HIF-1α and IL-1β expression in macrophages, an effect attenuated by glycolysis inhibition. Blocking TNF-α and IL-1β in RA serum diminished both glycolysis and IL-1β production. Our findings demonstrate that RA serum triggers aerobic glycolysis in macrophages, which promotes HIF-1α to drive IL-1β production. Notably, IL-1β within RA serum amplifies its own expression via this glycolysis-HIF-1α axis, establishing a pathogenic positive feedback loop in RA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"4 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141201","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":"Bone marrow lesion coexisted with subchondral bone attrition and/or subchondral bone cyst is associated with knee pain in knee osteoarthritis regardless of cartilage lesion: the Bunkyo health study","authors":"Jun Tomura, Haruka Kaneko, Arepati Adili, Takako Aoki, Lizu Liu, Yoshifumi Negishi, Keiichi Yoshida, Keiji Kobayashi, Suguru Wakana, Shinnosuke Hada, Jun Shiozawa, Yuichiro Machiyama, Takuya Yamamura, Takahiro Sasahara, Kengo Sugitani, Mitsuaki Kubota, Yuki Someya, Yoshifumi Tamura, Shuko Nojiri, Takako Negishi-Koga, Yasunori Okada, Muneaki Ishijima","doi":"10.1186/s13075-025-03644-2","DOIUrl":"https://doi.org/10.1186/s13075-025-03644-2","url":null,"abstract":"Subchondral bone changes, which include bone marrow lesion (BML), subchondral bone attrition (SBA) and subchondral bone cyst (SBC) by magnetic resonance imaging (MRI) analysis, are reportedly implicated for knee pain in knee osteoarthritis (OA). However, the relationship between these subchondral bone changes and OA knee pain and the effect of articular cartilage lesion on the pain remain elusive. Elderly subjects (1,145 subjects, 72.9 years old on average) in the Bunkyo Health Study, 71.5% of whom had knee OA with ≥ Kellgren-Lawrence grade 2, were enrolled. Knee pain in daily life over the past few days was measured using Visual Analogue Scale (VAS) in the Japanese Knee Osteoarthritis Measure. The subjects without or with pain were defined if they indicated a pain VAS score of 0 or a pain VAS score of ≥ 1. The association was examined between knee pain and MRI-detected OA structural changes which were determined according to the Whole Organ Magnetic Resonance Imaging Score. While 62.2% of the subjects were free from knee pain, 37.8% of the subjects had knee pain. Knee pain was not related with cartilage lesion without subchondral bone changes (odds ratio [OR]: 1.10 [95% confidence interval [CI]: 0.83–1.46]) or BML alone (OR: 1.32 [95% CI: 0.95–1.83]). However, knee pain was significantly associated with BML coexistent with SBA (OR: 2.22 [95% CI: 1.25–3.97]), SBC (OR: 1.79 [95% CI: 1.28–2.51]), or both SBA and SBC (OR: 2.18 [95% CI: 1.35–3.53]). Similar positive relationships between knee pain and coexisted subchondral bone changes were obtained regardless of the presence or absence of cartilage lesion present above the BML region. When BML was not coexistent with either SBA or SBC regardless of cartilage lesion above the subchondral bone changes, BML was not associated with knee pain (OR: 1.26 [95% CI: 0.90–1.77]) or (OR: 2.16 [95% CI: 0.89–5.23]). BML coexistent with SBA and/or SBC, but not BML without the coexistence, was associated with knee pain in the elderly with knee OA regardless of the presence or absence of cartilage lesion.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"42 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141565","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":"High-intensity exercise improves multidimensional fatigue and health-related quality of life in rheumatoid arthritis: a randomized controlled study","authors":"Annelie Bilberg, Jan Bjersing, Mats Börjesson, Jenny Sivertsson, Kaisa Mannerkorpi","doi":"10.1186/s13075-025-03643-3","DOIUrl":"https://doi.org/10.1186/s13075-025-03643-3","url":null,"abstract":"Prolonged fatigue is prevalent in people with rheumatoid arthritis (RA), and physical activity is recommended as an adjunct treatment option to managing fatigue. However, the type and dose of physical activity is not established. The purpose of this randomized controlled multicenter study was to evaluate the effect of high-intensity interval training (HIIT) and strength exercise on fatigue, sleep, mood, pain and health-related quality of life in people with RA. In total, 87 participants diagnosed with RA, mean age 48 (SD 9.66) Years and 84% females, were randomly assigned to an intervention group (IG) (n = 43) performing supervised HIIT and strength exercise for 12 weeks, or a control group (n = 44) with counseling of the general physical activity recommendations. Self-administered measures were assessed at baseline, 3 months, 6 months and 12 months; the Multidimensional Fatigue Inventory (MFI 20), the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression Scale (HADS), pain (VAS), health-related quality of life (VAS-global). Disease activity was assessed with the DAS28-ESR. Statistical analyses were performed using Analysis of Covariance (ANCOVA), and mixed model repeated measure analysis. At 3 months, a significant mean group difference in change was found on MFI-20 subscales General fatigue -4.0 (95%CI -5.57 to -2.39), Physical fatigue -4.9 (95%CI -6.43 to -3.36), Reduced activity -2.5 (95%CI -3.84 to -1.20), and Reduced motivation -1.8 (95%CI -2.97 to -0.62), favoring the IG. Additionally, a significant mean group difference in change was seen on VAS-global -12.8 (95%CI -21.3 to -4.3), in favor of the IG. At 6 months follow-up, the significant mean group difference on General fatigue -2.4 (95%CI -3.85 to -0.92), Physical fatigue -3.7 (95%CI -5.25 to -2.10), Reduced activity -2.0 (95%CI -3.53 to -0.39), Reduced motivation -1.6 (95%CI -2.93 to -0.16) and VAS-global -9.2 (95%CI -17.47 to -0.94) persisted. At 12 months follow-up a significant mean group difference was seen on Physical fatigue, depression mood, pain and VAS-global (p-value < 0.05), still in favor of the IG. The high-intensity exercise intervention had a beneficial effect on multidimensional fatigue, and health-related quality of life in people with RA. The effect on fatigue and health-related quality of life persisted during the 12 months-follow up period indicating long-term effects. The trial was registered prospectively on “FoU in Sweden” (Research and Development in Sweden), (registration number: 275642), and retrospectively on Trial Gov. (NCT 05768165).","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"105 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077419","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 diagnostic value and clinical relevance of salivary gland ultrasound in patients with highly suspected Sjögren’s Disease: a prospective monocentric study","authors":"Zhonghao Shi, Yimei Ding, Xiaoyan Dong, Guoling Li, Ben Li, Jiaqi Hou, Luan Xue","doi":"10.1186/s13075-025-03642-4","DOIUrl":"https://doi.org/10.1186/s13075-025-03642-4","url":null,"abstract":"To evaluate the diagnostic accuracy of salivary gland ultrasound (SGUS) in patients with high suspicion of Sjögren’s Disease (SjD) and to determine its potential role in the diagnostic process. This study is a cross-sectional diagnostic trial based on a prospective cohort, including 171 patients with high suspicion of SjD. SGUS of the parotid glands (PG) and submandibular glands (SMG) was performed according to the OMERACT scoring system. The predictive value of SGUS for diagnostic outcomes and labial salivary gland biopsy (LSGB) results was analyzed. The correlation between SGUS grading and unstimulated salivary flow rates (USFR) was also assessed using statistical tests. Of the 171 participants, 130 were diagnosed with SjD. The OMERACT total score demonstrated moderate efficacy in diagnosing SjD, with an area under the curve (AUC) of 0.78, a sensitivity of 0.52, and a specificity of 0.93. In comparison, LSGB showed the highest diagnostic efficacy (AUC = 0.90), followed by anti-Ro/SSA antibodies (AUC = 0.79). Combining the OMERACT total score with either anti-SSA antibodies or LSGB significantly improved diagnostic performance, achieving a specificity of 1.00. The diagnostic accuracy of parotid gland (PG) and submandibular gland (SMG) ultrasound grading was comparable. However, SMG grading exhibited higher sensitivity but lower specificity than PG grading. Additionally, SGUS grade 3 strongly predicted positive biopsy results (AUC = 0.77) and showed a significant correlation with USFR, with Spearman correlation coefficients of -0.45 for PG and -0.51 for SMG. Although the discriminatory efficacy of SGUS in patients highly suspected of SjD is suboptimal, SGUS may offer significant benefits for a specific subgroup of these patients. Grade 3 ultrasound findings are strongly associated with positive biopsy results and USFR, indicating a potential role in diagnosis and disease evaluation. SGUS may be considered for inclusion in future SjD classification criteria.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"45 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930709","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":"A 6-year prospective study on work participation and the associated factors in Dutch patients with systemic lupus erythematosus (SLE)","authors":"Birgit S. Blomjous, Marieke M. ter Wee, Michel W. P. Tsang-A-Sjoe, Cecile R. L. Boot, Alexandre E. Voskuyl, Irene E. M. Bultink","doi":"10.1186/s13075-025-03631-7","DOIUrl":"https://doi.org/10.1186/s13075-025-03631-7","url":null,"abstract":"Previous studies showed that many patients with SLE do not have paid work. However, having paid work is important for self-esteem, social contacts and income. It is therefore important to understand the characteristics contributing to work status and in particular identifying modifiable variables to help patients with SLE and their employers to maintain work. The objective of this study is to investigate associations of demographic, disease-related and work characteristics with having and maintaining paid work for ≥ 5 years in patients with SLE over a six-year period. All patients diagnosed with SLE, independent of disease duration and under treatment in Amsterdam UMC location VUmc or Reade were invited to participate in the longitudinal Amsterdam SLE cohort (2007–2018). Demographic, disease-related and work characteristics of these patients were analysed. Baseline was defined as the time of study entrance. Generalized Estimating Equations with logit link function were used to identify associations between these characteristics on having paid work. Logistic regression was used to study associations with maintenance of work and work disability. At baseline, 52% of patients (114/220) were employed, which decreased to 46% (73/157) after six years. The main reported reason for unemployment was because of SLE-related symptoms (63%). Among the 106 patients who were unemployed at baseline, 16% (17/106) gained work during follow-up of whom 47% (8/17) also maintained work. Of the 114 patients employed at baseline, 29% (33/114) remained employed throughout the entire six-year follow-up period. Having paid work over time was associated with younger age, higher level of education, shorter disease duration, lower organ damage and supervisor support. Maintaining employment for ≥ 5 years during follow-up was associated with regular working hours, skill discretion, decision authority and decision latitude. A longer disease duration was associated with work disability at baseline. This study shows that alongside demographic and disease-related characteristics, also work characteristics are associated with having and maintaining paid work in SLE patients. These characteristics should be taken into consideration when developing interventions to improve sustainable employability in patients with SLE. 1. The unemployment rate in SLE patients is high (54%) and increased over time during follow-up. 2. Maintaining work is associated with more supervisor support, regular working hours, skill discretion, decision authority, decision latitude. 3. Of the unemployed SLE patients at baseline, 16% started working of whom 47% maintained work.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"35 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928088","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":"Transforming growth factor beta (TGF-β) induces type 1 interferon signalling in systemic sclerosis keratinocytes through the chloride intracellular channel 4 (CLIC4)","authors":"Christopher W. Wasson, Sophie L. Dibb, Begoña Caballero-Ruiz, Ifeoluwa E. Bamigbola, Stefano Di Donato, Eva M. Madourie-Clavane, Rebecca Wells, Vishal Kakkar, Enrico De Lorenzis, Jessica Bryon, Emma Derrett-Smith, Christopher P. Denton, Yasser El-Sherbiny, Paul J. Meakin, Rebecca L. Ross, Francesco Del Galdo","doi":"10.1186/s13075-025-03632-6","DOIUrl":"https://doi.org/10.1186/s13075-025-03632-6","url":null,"abstract":"Systemic sclerosis (SSc) is an autoimmune disease, which is characterized by fibrosis of the skin, progressing to affect the internal organs in the most serve cases. Type 1 interferon (IFN) signalling plays a major role in SSc disease progression. The cytokine TGF-β has been extensively shown to be a major driver of fibrosis but its role in the induction of the type 1 interferon response is poorly understood. Type 1 IFN signalling was activated in keratinocytes using a range of agonists, IFN2α, Poly I:C, Poly dA:dT, LPS and TGF-β. CLIC4 activity was inhibited with the small molecule chloride channel inhibitors NPPB, IAA:94 and siRNA specific to CLIC4. Conditioned media collected from Healthy and SSc dermal fibroblasts was used to stimulate keratinocytes. TGF-β stimulation induces a type 1 IFN response in keratinocytes, dependent on the chloride intracellular channel 4 (CLIC4). Inhibition of CLIC4 via small molecule inhibitors or siRNA attenuates TGF-β mediated activation of Signal Transducer and Activator of Transcription 1 (STAT1) in keratinocytes. Further analysis revealed SSc dermal fibroblasts induce a type 1 IFN response in keratinocytes in part through a TGFβR1-CLIC4 axis. This study shows the ability of CLIC4 to enhance TGF-β signalling is essential for aberrant type 1 interferon signalling in SSc skin.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"26 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923971","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":"Regulation of fibroblast-like synoviocyte function by cadherin 6 in rheumatoid arthritis","authors":"Camilla R. L. Machado, Eunice Choi, Narayanan B. Perumal, Robert J. Benschop, Gregory R. Dressler, Wei Wang, David L. Boyle, Gary S. Firestein","doi":"10.1186/s13075-025-03637-1","DOIUrl":"https://doi.org/10.1186/s13075-025-03637-1","url":null,"abstract":"Cadherins (CDH), such as CDH11, are glycoprotein adhesion molecules contributing to cell-cell interactions in health and disease. CDH11 has demonstrated important functions in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). In transcriptome expression studies, we observed that Cadherin 6 (CDH6) expression was higher in RA compared to osteoarthritis (OA). CDH6 is associated with cancer progression, but little information is known on the role of CDH6 in RA. The present study investigates CDH6 expression, regulation, function in FLS, and distribution in RA synovia. Synovial tissue and FLS were obtained from RA or OA patients undergoing joint replacement. CDH6 epigenetic marks and expression in RA and OA FLS were evaluated using public databases. CDH6 expression was determined by RT-PCR, Western blot, and immunostaining. RA and OA FLS were stimulated with cytokines and growth factors, and CDH6 mRNA expression was determined. CDH6 was silenced using siRNA, and the effect on migration, cell growth, apoptosis, autophagy, cell cycle, and signaling was studied. In our analysis of cadherin family expression, CDH6 expression was higher in RA than OA FLS. This was associated with differential chromatin accessibility and histone marks in the CDH6 promoter of RA FLS. H3K27ac was identified as an important regulator of CDH6 expression in RA FLS based on experiments using histone deacetylase inhibitors. TGFß, but not IL-1β, TNF, IL-17A, IFNγ, IL-6, or PDGF, increased CDH6 expression of cultured RA FLS. CDH6 knockdown significantly decreased RA FLS migration and cell growth. The latter was associated with increased apoptosis in CDH6 deficient FLS. Immunofluorescence showed CDH6 protein distribution in the membrane, perinuclear, and nuclear regions of cultured FLS. In RA synovial tissue, CDH6 expression was noted in FLS and macrophages within the lining and sublining regions. CDH6 expression is elevated in RA FLS due to epigenetic and local conditions of synovitis promoting migration, survival and cell growth, which are characteristic features of aggressive RA FLS. The intracellular distribution suggests additional functions beyond adhesion and homotypic aggregation, such as signaling and gene regulation. These data suggest CDH6 contributes to RA pathogenesis by influencing pathologic FLS behavior and could be a therapeutic target.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"21 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915499","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":"Expression of thrombospondin-4 in the infrapatellar fat pad and synovial fluid – potential contribution to osteoarthritis pain","authors":"Sebastian Braun, Patrizia Pollinger, Rebecca Sohn, Anna E. Rapp, Gundula Rösch, Frank Zaucke, Zsuzsa Jenei-Lanzl","doi":"10.1186/s13075-025-03615-7","DOIUrl":"https://doi.org/10.1186/s13075-025-03615-7","url":null,"abstract":"During osteoarthritis (OA) pathogenesis, the infrapatellar fat pad (IFP) undergoes fibrotic changes that might contribute to pain development. Recent studies have demonstrated that thrombospondin-4 (TSP-4), first detected in the extracellular matrix of cartilage and released during its degradation, has been implicated in the pathogenesis of pain. Therefore, we analyzed TSP-4 levels in the IFP and synovial fluid and correlated this data with IFP fibrosis and knee joint pain. IFP and synovial fluid were collected from patients undergoing total knee replacement surgery. Total WOMAC total and pain scores were determined preoperatively. IFP sections were stained using standard Masson trichrome and hematoxylin/eosin dyes to assess fibrotic changes, number of vessels and lymphocytic infiltration. TSP-4 expression in the IFP was detected immunohistochemically. TSP-4 in synovial fluid samples was quantified using ELISA. TSP-4 was detectable in human IFP tissue at the protein level and its expression levels showed a positive correlation with the degree of tissue fibrosis. Regarding the degree of fibrosis and TSP-4-stained areas, four patient subgroups could be distinguished. Notably, moderate levels of TSP-4 expression were already detectable in samples exhibiting a low degree of fibrosis. There was no significant correlation between TSP-4 staining intensity in IFP and pain. There was no correlation between TSP-4 staining intensity and synovial fluid TSP-4 concentrations. A significant relationship between synovial fluid TSP-4 concentration and pain intensity was only found in female OA patients. TSP-4 has been detected in the IFP for the first time. The correlation between TSP-4 expression and fibrotic severity indicates a possible involvement of TSP-4 in the development of fibrosis. Although TSP-4 within the IFP may not directly mediate pain, its presence in synovial fluid could be of functional relevance in pain-related mechanisms. Further analysis of synovial fluid and even serum samples from larger patient populations will determine whether TSP-4 could serve as a biomarker for pain or potentially represent a novel target for analgesic therapies.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"37 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899592","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}