Arthritis Research & Therapy最新文献

{"title":"Differences in the response to TNF inhibitors at distinct joint locations in patients with psoriatic arthritis: results from nine European registries","authors":"Adrian Ciurea, Seraphina Kissling, Andrea Götschi, Lykke Midtbøll Ørnbjerg, Simon Horskjær Rasmussen, Bálint Tamási, Burkhard Möller, Michael J. Nissen, Bente Glintborg, Anne Gitte Loft, Almut Scherer, René Bräm, Karel Pavelka, Jakub Závada, Joao Madruga Dias, Paula Valente, Bjorn Gudbjornsson, Olafur Palsson, Vappu Rantalaiho, Ritva Peltomaa, Catalin Codreanu, Corina Mogosan, Florenzo Iannone, Marco Sebastiani, Gareth T. Jones, Gary J. Macfarlane, Isabel Castrejon, Ziga Rotar, Brigitte Michelsen, Johan K. Wallman, Irene van der Horst-Bruinsma, Oliver Distler, Mikkel Østergaard, Merete Lund Hetland, Raphael Micheroli, Caroline Ospelt","doi":"10.1186/s13075-025-03488-w","DOIUrl":"https://doi.org/10.1186/s13075-025-03488-w","url":null,"abstract":"Efficacy of tumour necrosis factor inhibitors (TNFi) for peripheral arthritis in patients with psoriatic arthritis (PsA) has been established in randomized clinical trials that have used improvement in summated joint counts as an outcome. Whether joints at different anatomical locations might respond differentially to TNFi remains unknown. The aim of the study was to investigate potential variations in the responsiveness to a first tumour necrosis factor inhibitor (TNFi) among joints at distinct locations in patients with psoriatic arthritis (PsA) treated in routine clinical care. Bionaive PsA patients from nine European countries were included in this observational cohort study if ≥ 1 joint was swollen at the initiation of a first TNFi as monotherapy or added to methotrexate. Only the 28-joint count was available without imaging data confirming the presence of synovitis. The primary outcome was time to first resolution of joint swelling at each joint level. Hazard ratios (HR) for resolution comparing different joint locations were estimated using interval-censored mixed-effects Cox proportional hazards models, including a random effect for country and patient, adjusted for age and sex. A total of 1729 patients with 8397 swollen joints at the start of TNFi were included. Considering the upper extremity, a higher rate of resolution of joint swelling (HR, 95% CI) was observed for the shoulder (1.65, 1.16–2.35) and elbow (1.90, 1.38–2.61), while a lower rate was found for the wrist (0.72, 0.62–0.83) compared to the joints of digit 3. Within fingers, and using the same reference, joint swelling resolved fastest in digit 4 (1.77, 1.49–2.11) and digit 5 (1.88, 1.53–2.31). A lower rate of resolution of joint swelling was found for the knee in comparison to the elbow, the corresponding joint on the upper limb (0.56, 0.40–0.78). The time to resolution of joint swelling upon treatment with TNFi in patients with PsA seems to depend on the localisation of the affected joints.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"37 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072156","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":"Performance of the modified 2022 ACR/EULAR giant cell arteritis classification criteria without age restriction for discriminating from Takayasu arteritis","authors":"Takahiko Sugihara, Masayoshi Harigai, Haruhito A. Uchida, Hajime Yoshifuji, Yasuhiro Maejima, Jun Ishizaki, Yoshiko Watanabe, Hiroaki Dobashi, Yoshinori Komagata, Naoto Tamura, Yoshikazu Nakaoka","doi":"10.1186/s13075-025-03486-y","DOIUrl":"https://doi.org/10.1186/s13075-025-03486-y","url":null,"abstract":"To evaluate the ability to discriminate giant cell arteritis (GCA) from Takayasu arteritis (TAK) according to the modified 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) GCA classification criteria. Patients enrolled in the Japanese nationwide retrospective registry were evaluated using the criteria with partial modification; wall thickening of descending thoracic-abdominal aorta were mainly diagnosed by contrast-enhanced computed tomography (CT) or magnetic resonance imaging instead of evaluating with positron emission tomography (PET)-CT. The discriminability of the criteria was evaluated using C-statistic (> 0.7: good ability). Newly diagnosed patients with GCA (n = 139) and TAK (n = 129) were assessed, and 23.3% of TAK were aged 50 years or older at onset. The sensitivity of the modified 2022 ACR/EULAR GCA classification criteria with a score ≥ 6 was 82.0%, 68.5%, and 32.1% in all GCA, GCA with large-vessel involvement, and GCA without cranial arteritis, respectively. The specificity of the modified criteria was 96.1% for the 129 TAK as controls. Five patients with late-onset TAK met the modified criteria, and four had cranial signs and symptoms, two had bilateral axillary artery involvement, and four had descending thoracic-abdominal aorta involvement. The discriminability of the criteria was good (C-statistic: 0.986, 95% confidence interval [CI]: 0.976–0.996) and remained good after excluding age (C-statistic: 0.927, 95% CI: 0.894–0.961). The discriminability of a set of large-vessel lesions (bilateral axillary artery and descending thoracic-abdominal aorta) and inflammatory markers was markedly decreased with poor C-statistic value (C-statistic: 0.598, 95% CI: 0.530–0.667). Discriminability was improved after adding polymyalgia rheumatica (PMR) (C-statistic: 0.757, 95% CI: 0.700–0.813) or age (C-statistic: 0.913, 95%CI: 0.874–0.951) to the set of large-vessel lesions. In GCA patients with a score ≤ 5, 52% had bilateral subclavian and/or axillary artery involvement. The modified 2022 ACR/EULAR GCA classification criteria well performed in classifying GCA and TAK without PET-CT in routine clinical practice. A set of items included in the modified GCA classification criteria had good discriminative ability for GCA and TAK, even when age was excluded. However, age restriction or PMR was required to distinguish GCA without cranial lesions from TAK.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"50 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072155","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":"Diagnostic performance of optical spectral transmission compared to magnetic resonance imaging in patients with inflammatory arthritis","authors":"Konstantinos Triantafyllias, Mohammed Alhaddad, Andreas Schwarting, Veronika Balaklytska, Xenofon Baraliakos","doi":"10.1186/s13075-025-03478-y","DOIUrl":"https://doi.org/10.1186/s13075-025-03478-y","url":null,"abstract":"Optical spectral transmission (OST) is a modern diagnostic method capable of quantifying inflammation in the finger and wrist joints of arthritis patients by assessing the blood-specific absorption of light transmitted through a tissue. The diagnostic performance of this modality has not been adequately examined and data regarding OST associations with magnetic resonance imaging (MRI) are limited. Aim of this study was therefore to investigate the performance of OST in assessing joint inflammation as compared to MRI in patients with inflammatory arthritis (IA). Data from patients who underwent MRI and OST for suspected IA were analyzed. For comparison, a historical healthy control (HC) group with OST was also accounted. MRI findings were quantified using the Rheumatoid Arthritis MRI Score (RAMRIS). Diagnostic accuracy of OST was evaluated using Receiver Operating Characteristics (ROC), while correlation analyses were conducted to explore relationships between OST and MRI, as well as disease activity markers. Overall, 71 patients with known rheumatic diseases (n = 1,542 wrist and finger joints) and 114 HC (n = 2,508 joints) subjects were included. 51 patients showed inflammatory signs on MRI (MRI+). These also showed significantly higher OST scores (16.41 ± 5.53) than subjects without MRI inflammation (MRI-) (11.52 ± 5.03) or HC (10.78 ± 4.19) (all; p < 0.001). OST showed significant correlations with RAMRIS-synovitis and tenosynovitis scores in the MRI + group (rho = 0.541, p < 0.001; rho = 0.341, p = 0.01, respectively). Significant correlations were observed between OST and clinical parameters for disease activity. Using MRI as a reference, the best diagnostic value of OST was observed at the wrist level in the MRI + group, by an AUC of 0.833 (95%CI 0.700-0.966). OST showed an excellent performance compared to MRI and correlated significantly with RAMRIS scores and clinical parameters in IA patients, also differentiating IA from HC.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"30 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056613","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":"GPIHBP1 increase accounts for rheumatic arthritis-related hypotriglyceridemia by facilitating lipids uptake of white adipose tissues","authors":"Meng-Ke Song, Meng-Fan Gu, Ling Liu, Lian-Jun He, Peng Ye, Kui Yang, Dan-Dan Wang, Opeyemi Joshua Olatunji, Qin Yin, Jian Zuo","doi":"10.1186/s13075-025-03483-1","DOIUrl":"https://doi.org/10.1186/s13075-025-03483-1","url":null,"abstract":"Metabolism alteration is a common complication of rheumatic arthritis (RA). This work investigated the reason behind RA-caused triglyceride (TG) changes. Fresh RA patients’ whole blood was transfused into NOD-SCID mice. Metabolism-regulatory tissues were examined after sacrifice. To verify the findings, tissues of the rats with long-lasting adjuvant-induced arthritis (AIA) were analyzed. Some rats were injected with human plasma and GPIHBP1, and their blood TG was monitored. Various cells were stimulated by cytokines or rheumatic subjects’ serum. Some pre-adipocytes were cultured by human serum or in the presence of HUVEC cells and GPIHBP1. TG decrease occurred in blood and white adipose tissues (WAT) of the RA blood-transfused NOD-SCID mice and chronic AIA rats. Fatty acids (FA) oxidation in muscles was accelerated a bit, while TG catabolism status in their livers was varied. TNF-α, IL-1β, IL-6 and RA/AIA serum promoted expression of TG utilization-related enzymes and FA uptake transporters in pre-adipocytes, but barely affected LPL. Mild IL-6 stimulus promoted GPIHBP1 release of HUVEC cells. GPIHBP1 was increased in RA serum. This change can decrease blood TG in rats, which was overshadowed by an injection of excessive GPIHBP1. RA serum slightly inhibited LPL secretion in pre-adipocytes. Both HUVEC cells co-culture and GPIHBP1 supplement reduced LPL distribution on pre-adipocytes, and eliminated LPL activity difference between normal and RA serum-treated cells. No TG uptake difference was observed in these circumstances. RA-associated inflammation induces GPIHBP1 secretion of endothelial cells, which facilitates blood TG hydrolysis and uptake to compensate the loss in WAT.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"8 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031091","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":"Exploring the therapeutic effect of human recombinant IL11 on lesioned OA human osteochondral explants","authors":"Margo Tuerlings, Evelyn Houtman, Elisa J.H. Muusers, Janneke Simon, Maurice W. de Haan, Ilja Boone, Yolande F.M. Ramos, Rachid Mahdad, Ingrid Meulenbelt","doi":"10.1186/s13075-025-03480-4","DOIUrl":"https://doi.org/10.1186/s13075-025-03480-4","url":null,"abstract":"To explore IL11 co-expression profiles in our previously reported RNA-sequencing dataset of OA articular cartilage, in interaction with IL6, and to investigate the effects of hrIL11 administration as potential therapeutic strategy for OA articular cartilage using our biomimetic aged human osteochondral explant model of OA. We used RNA-sequencing datasets of macroscopically preserved and lesioned OA articular cartilage (N = 35 patients). Spearman correlations were calculated between IL11 and IL6 expression levels and genes expressed in cartilage (N = 20048 genes). Osteochondral explants were isolated from macroscopically preserved and lesioned areas of the joint and were kept in culture for two weeks, with or without exposure to 200ng/ml hrIL11. We found no overlap in correlating genes between IL11 and IL6, indicating their distinct roles in articular cartilage. Moreover, we identified more genes being correlated to IL11 in the lesioned compared to preserved articular cartilage (N = 203 and 106 genes, respectively). Upon treatment of ex vivo OA articular cartilage with hrIL11, we overall observed unbeneficial effects on chondrocyte phenotype, as illustrated by upregulation of MMP13, EPAS1, RUNX2, and POSTN. We did not observe significant differences in Mankin scores upon addition of hrIL11. The current study showed that treatment of OA articular cartilage with hrIL11 is unlikely to be beneficial despite previous indications of hrIL11 as potential druggable target. These findings underscore the importance of functionally investigating OA risk genes. Better understanding of IL11 signaling and the underlying pathways is necessary towards the development of OA treatment strategy.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"63 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027231","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":"Cancer incidence and the influence of immunosuppressive agents in Korean patients with systemic lupus erythematosus: a retrospective cohort study","authors":"Soo-Kyung Cho, Jung-Yong Han, Yena Jeon, Seung-Hun You, Sun-Young Jung, Eun Jin Jang, Yoon-Kyoung Sung","doi":"10.1186/s13075-025-03482-2","DOIUrl":"https://doi.org/10.1186/s13075-025-03482-2","url":null,"abstract":"To investigate cancer incidence and the potential influence of immunosuppressive agents in Korean systemic lupus erythematosus (SLE) patients. We conducted a retrospective analysis utilizing data from the Korea Healthcare Bigdata Linked Platform, which integrated the National Central Cancer Registry and National Health Insurance Service databases covering the period 2008–2017. Incidence rates (IRs) per 10,000 person-years (PYs) for site-specific cancers of SLE patients were calculated using ICD-O-3 codes. Multivariable logistic regression analysis was utilized to assess the association between immunosuppressive agents and cancer development in SLE patients. A total of 10,013 predominantly female (91%) Korean SLE patients with a mean age of 36.9 ± 15.2 years were included. During a follow-up of 62,268.5 PYs, 368 patients developed cancer. The IRs per 10,000 PYs for total, solid, and hematologic cancers were 59.07, 54.09, and 5.78, respectively. The most prevalent cancers (measured in IRs per 10,000 PYs) were thyroid (17.01, 95% CI 13.78–20.25), breast (8.67, 95% CI 6.36–10.98), stomach (4.49, 95% CI 2.83–6.16), colorectal (4.17, 95% CI 2.57–5.78), and cervical (3.85, 95% CI 2.31–5.39). Approximately half (50.8%) of SLE patients with cancer were diagnosed at the localized Surveillance, Epidemiology, and End Results (SEER) stage. No statistically significant association was found between immunosuppressive agents and cancer development (Odds Ratio 1.03, 95% CI 0.80–1.34). Our study shows that Korean SLE patients using immunosuppressive agents are not significantly more likely to develop cancer. Further research with extended observation is warranted to corroborate these findings.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"33 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992746","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":"Suberosin attenuates rheumatoid arthritis by repolarizing macrophages and inhibiting synovitis via the JAK/STAT signaling pathway","authors":"Huan Liu, Qianwei Li, Yuehong Chen, Min Dong, Hongjiang Liu, Jiaqian Zhang, Leiyi Yang, Geng Yin, Qibing Xie","doi":"10.1186/s13075-025-03481-3","DOIUrl":"https://doi.org/10.1186/s13075-025-03481-3","url":null,"abstract":"Rheumatoid arthritis (RA) is a systemic disease that primarily manifests as chronic synovitis of the symmetric small joints. Despite the availability of various targeted drugs for RA, these treatments are limited by adverse reactions, warranting new treatment approaches. Suberosin (SBR), isolated from Plumbago zeylanica—a medicinal plant traditionally used to treat RA in Asia—possesses notable biological activities. This study aimed to investigate the effects and potential underlying pathways of SBR on RA. Tumor necrosis factor-alpha (TNF-α) induced inflammation in RA-derived fibroblast-like synoviocytes (RA-FLS), and the expression of proinflammatory mediators was assessed using q-RT PCR and ELISA after treatment with various SBR concentrations. Bone marrow-derived macrophages (BMDMs) were induced to differentiate into M1 and M2 macrophages, followed by treatment with various SBR concentrations and macrophage polarization assessment. Low-dose (0.5 mg/kg/d) and high-dose (2 mg/kg/d) SBR regimens were administered to a collagen-induced arthritis (CIA) mouse model for 21 days, and the anti-arthritic effects of SBR were evaluated. Network pharmacology and molecular docking analyses were used to predict the anti-arthritic targets of SBR. The effect of SBR on the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway was evaluated. SBR suppressed macrophage polarization toward the M1 phenotype while enhancing their polarization toward the M2 phenotype. SBR reduced the levels of proinflammatory mediators in TNF-α-induced RA-FLS. Mechanistically, SBR inhibited the phosphorylation of the JAK1/STAT3 signaling pathway in RA-FLS and M1 macrophages and promoted the phosphorylation of the JAK1/STAT6 pathway in M2 macrophages, enhancing M2 polarization. In vivo, prophylactic treatment of low-dose SBR reduced M1 macrophage infiltration into synovial tissue, increased the proportion of M2 macrophages, and decreased the expression of inflammatory mediators in the serum and synovial tissue, alleviating synovial inflammation. SBR significantly alleviated arthritis in CIA mice through macrophage repolarization and inhibition of inflammation. SBR significantly reduced clinical symptoms, joint pathological damage, and expression inflammatory cytokine expression in CIA mice. SBR exhibited anti-arthritic effects via the JAK1/STAT3 and JAK1/STAT6 signaling pathways, inhibiting synovial tissue inflammation and M1 macrophage polarization while promoting M2 macrophage polarization. Therefore, SBR may be an effective candidate for RA treatment.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"9 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990931","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":"Do individuals with inflammatory arthritis receive minimally adequate treatment for incident depression and anxiety: A population-based study","authors":"Alyssa Howren, Eric C. Sayre, J. Antonio Avina-Zubieta, Joseph H. Puyat, Deborah Da Costa, Hui Xie, Eileen Davidson, Amit Gupta, Mary A. De Vera","doi":"10.1186/s13075-024-03466-8","DOIUrl":"https://doi.org/10.1186/s13075-024-03466-8","url":null,"abstract":"Describe patterns of pharmacotherapy and psychological treatment and evaluate receipt of minimally adequate treatment for incident depression and anxiety in individuals with inflammatory arthritis (IA). We used population-based linked administrative health databases from British Columbia, Canada to evaluate pharmacotherapy and psychological treatments for incident depression and/or anxiety among individuals with IA and without IA (‘IA-free controls’). We defined minimally adequate pharmacotherapy as antidepressant prescriptions filled with ≥ 84 days’ supply and adequate psychological treatment as ≥ 4 counselling/psychotherapy services. Multivariable logistic regression models were used to evaluate the odds of individuals with IA receiving minimally adequate pharmacotherapy and/or psychological treatment compared to IA-free controls. 6,951 (mean age 54.8 ± 18.3 years; 65.5% female) individuals with IA had incident depression and 3,701 (mean age 52.9 ± 16.8 years; 74.3% female) had incident anxiety. Minimally adequate pharmacotherapy and psychological treatment for depression was respectively observed in 50.5% and 19.6% of those with IA, proportions similar to IA-free controls (pharmacotherapy: aOR 1.10, 95% CI 1.00 to 1.21; psychological: aOR 1.07, 95% CI 0.94 to 1.21). Results were similar regarding anxiety treatment. Individuals with IA had a significantly greater likelihood of dispensing ≥ 1 benzodiazepine (anxiety: IA 45.0%, IA-free controls 39.0%, p-value < 0.001) and ≥ 1 tricyclic antidepressant prescription (anxiety: IA 12.8%, IA-free controls 7.8%, p-value < 0.001). Significantly higher average days’ supply of benzodiazepines was observed for IA (anxiety: IA 123.7 days, controls 112.4 days, p-value = 0.003). A substantial proportion of individuals with IA were not receiving adequate mental health treatment for depression and anxiety, a finding similar for IA-free controls. The undertreatment of mental disorders for people with IA has well-known negative implications for the provision of effective rheumatology care. It remains fundamental to expand publicly funded health care to include mental health services in an effort to address unmet counselling needs.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"37 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990928","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":"Exosome miR-199a-5p modulated vascular remodeling and inflammatory infiltration of Takayasu’s arteritis","authors":"Shuning Guo, Jiehan Li, Shurui Pang, Jing Li, Xinping Tian","doi":"10.1186/s13075-025-03475-1","DOIUrl":"https://doi.org/10.1186/s13075-025-03475-1","url":null,"abstract":"Advances in treatment have swiftly alleviated systemic inflammation of Takayasu’s arteritis (TAK), while subclinical vascular inflammation and the ensuing arterial remodeling continue to present unresolved challenges in TAK. The phenotypic switching of vascular smooth muscle cells (VSMC) is regarded as the first step in vascular pathology and contributes to arterial remodeling. Exosomes facilitate the transfer and exchange of proteins and specific nucleic acids, thereby playing a significant role in intercellular communication. Little is known about the modulatory role of serum exosomes in phenotypic switching of VSMC and vascular remodeling in TAK. Serum exosomes isolated from TAK patients were co-cultured with VSMC to identify the modulatory role of exosomes. VSMC were transfected with miR-199a-5p mimic and inhibitor. CCK8 assays and EdU assays were performed to measure proliferative ability. The migration of VSMC was evaluated by scratch assays and transwell migration assays. The flow cytometry was employed to identify apoptosis of VSMC. Dual-luciferase reporter assay, RNA immunoprecipitation assay and fluorescence in situ hybridization were utilized to validate the target gene of miR-199a-5p. The correlational analysis was conducted among exosome miRNA, serum MMP2, TIMP2 and clinical parameters in TAK patients. The coculture of VSMC with serum exosome mediated dedifferentiation of VSMC. Through gain- and loss-of-function approaches, miR-199a-5p over-expression significantly increased expression of VSMC marker genes and inhibited VSMC proliferation and migration, whilst the opposite effect was observed when endogenous miR-199a-5p was knocked down. The overexpression of miR-199a-5p suppressed VSMC apoptosis. Further, MMP2 serves as functional target gene of miR-199a-5p. The correlation analyses revealed an inverse correlation between Vasculitis Damage Index and exosome miR-199a-5p level or serum MMP2, which requires validation in a larger cohort. Our study indicated that the miR-199a-5p/MMP2 pathway played a role in inhibiting the migration, proliferation and apoptosis of VSMC. The decreased secretion of MMP2 may potentially prompt the intimal infiltration of inflammatory cells within the vascular wall, offering a novel therapeutic opportunity by tackling both inflammatory responses and the neointimal overgrowth associated with TAK arterial damage. Moreover, exosome miR-199a-5p and MMP2 derived from serum possess potential as future biomarkers for vascular injury.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"56 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989944","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 serum level of sclerostin decreases in radiographic axial spondyloarthritis patients with fatty lesions","authors":"Xuegang Li, Haijian Jiang, Xu Wang, Shuping Zhong","doi":"10.1186/s13075-025-03479-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03479-x","url":null,"abstract":"Currently, the pathophysiology of new bone formation in radiographic axial spondyloarthritis (r-axSpA) remains unclear. Cellular elements and their secreted bone turnover markers might be one of the underlying mechanisms that drive the new bone formation. Our study aimed to investigate the role of bone turnover markers in r-axSpA patients with fatty lesions. 73 r-axSpA patients were enrolled in this study. 48 and 25 patients were divided into r-axSpA group with and without fatty lesions. Clinical variables were collected and all patients received comprehensive rheumatologic assessment for disease activity, including Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Axial Spondyloarthritis Disease Activity Score (ASDAS). Fatty lesions in the sacroiliac joints (SIJs) were scored independently by two radiologists. Serum levels of bone turnover markers, including sclerostin, osteoprotegerin (OPG), procollagen I N-terminal propeptide (PINP), cross linked C-telopeptide of type I collagen (CTX-I), osteocalcin (OC), were measured using enzyme-linked immunosorbent assays. There were no significant differences between two groups in terms of gender, age, body mass index (BMI), duration, smoking, HLA-B27 positivity rate, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), BASDAI, ASDAS-ESR, ASDAS-CRP, biological disease-modifying anti-rheumatic drugs (bDMARDs) rate. No significant differences were observed in terms of OPG, PINP, CTX-I or OC between two groups. The mSASSS were higher in fatty lesions group than in those without fatty lesions (p < 0.001). The serum sclerostin levels were significantly lower in r-axSpA patients with fatty lesions than in those without fatty lesions (p < 0.001). There were correlations between BMI, mSASSS and sclerostin with the comprehensive Berlin scoring method (CBM) scores in the univariate analysis (ρ = 0.311, ρ = 0.306, ρ = -0.920, respectively). However, only sclerostin had correlation with the CBM scores in multivariate analysis (ρ = -0.040, p < 0.001). In the r-axSpA patients with fatty lesions, serum sclerostin levels are declined. Serum sclerostin might be useful as a biomarker to predict the progression of the chronic inflammation in SIJs in r-axSpA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"118 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987591","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}