Arthritis Research & Therapy最新文献

{"title":"Serum tryptophan-kynurenine metabolites served as biomarkers of disease activity in rheumatoid arthritis and linked to immune imbalance","authors":"Ruihe Wu, Baochen Li, Rui Su, Xiaoyang Liu, Anqi Gao, Jing Luo, Chong Gao, Xiaofeng Li, Caihong Wang","doi":"10.1186/s13075-025-03596-7","DOIUrl":"https://doi.org/10.1186/s13075-025-03596-7","url":null,"abstract":"Immune imbalance caused by imbalanced helper T(Th)17/regulatory T (Treg) and follicular helper T (Tfh)/follicular regulatory T (Tfr) cells drives the onset of rheumatoid arthritis (RA) fundamentally. Tryptophan (Trp) metabolism is crucial in regulating immune and altered Trp metabolism has been reported in RA. However, the potential of altered Trp metabolites to serve as RA-related biomarkers and their relationship to immune balance in RA remains undetermined. We explored the Trp metabolic characteristics in RA by comparing the targeted quantitative Trp metabolomics between 29 new-onset RA patients and 19 healthy controls (HCs). The RA-related disease biomarkers from Trp metabolites were identified to construct a classification model through machine learning algorithms. Their association with immune imbalance in RA was analyzed. Differential analysis exhibited significant alterations in serum Trp metabolites and metabolic pathways between RA and HCs. There were 7 differential metabolites of serum Trp, which were all decreased in RA (P < 0.05). Trp metabolic pathways analysis indicated that the Trp-Kynurenine(Kyn) pathway was downregulated in RA(P < 0.05). And the key enzyme of the Trp-Kyn pathway, indoleamine-2,3-dioxygenase1 (IDO1), was reduced in RA (P < 0.05). Altered Trp metabolites especially those from the Trp-Kyn pathway exhibited a negative correlation with the clinical indicators and autoantibody expression. 4 Trp metabolites from the Trp-Kyn pathway including Trp, xanthurenic acid (XA), cinnabarinic acid (CA) and kynurenic acid (KynA) were identified as RA-related disease biomarkers to construct RA-HC classification model, which exhibited good ability to distinguish RA from HCs (AUC = 0.951, 95%CI = 0.897-1.000) and stratify disease activity of RA. In addition, these Trp-Kyn pathway metabolites were also associated with the immune imbalance of RA. Specifically, reduced Trp and XA were negatively related to the imbalanced Th17/Treg cells, and reduced KynA was negatively associated with the imbalanced Tfh/Tfr cells. And the reduced IDO1 was also negatively correlated to the imbalanced Tfh/Tfr cells. Altered Trp-Kyn metabolism might contribute to the pathogenesis of RA. We highlighted the association of the Trp-Kyn metabolic pathway with immune imbalance in RA and its potential value in clinical practice, particularly in early diagnosis, disease activity monitoring, and personalized treatment.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565645","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":"Retention rate of TNF inhibitors versus IL-17 inhibitors in ankylosing spondylitis patients with prior biologics experience.","authors":"Jiwon Yang, Bong-Woo Lee, Youngjae Park, Ji Hyeon Ju, Wan-Uk Kim, Sung-Hwan Park, Seung-Ki Kwok, Jennifer Jooha Lee","doi":"10.1186/s13075-025-03601-z","DOIUrl":"10.1186/s13075-025-03601-z","url":null,"abstract":"<p><strong>Background: </strong>For patients with ankylosing spondylitis (AS) who experience inefficacy or adverse events with biologics, no recommendations exist regarding the preference for class cycling or switching as a second- or higher-line biologics. Previous studies on the drug retention of TNF and IL-17 inhibitors in AS patients with prior biologics exposure have limitations, including relatively short follow-up periods, exclusion of patients with extra-articular manifestations, and a primary focus on second-line treatment. This study aimed to compare the retention rates of TNF and IL-17 inhibitors in AS patients with prior biologics experience, over a relatively longer follow-up period in real clinical practice.</p><p><strong>Methods: </strong>A total of 148 AS cases receiving either a TNF or IL-17 inhibitor as a second- or higher-line biologic were retrospectively analyzed after propensity score matching. Patient characteristics at the time of cycling or switching and drug retention were compared between the two groups. Subgroup analyses were conducted based on the reasons for drug discontinuation. Cox regression analyses were used to identify the factors associated with drug discontinuation.</p><p><strong>Results: </strong>The median follow-up period was 31.4 months, and drug survival tended to be lower for IL-17 inhibitors than for TNF inhibitors in the Kaplan-Meier analysis (P = 0.134). The lower retention of IL-17 inhibitors was more pronounced when discontinuations unrelated to treatment failure were censored (P = 0.034) or when used for reasons other than psoriasis aggravation (P = 0.028). However, in multivariable Cox regression, the number of previous biologics (HR: 1.62, 95% CI: 1.17-2.23, P = 0.003) and BASDAI (HR: 1.3, 95% CI: 1.03-1.65, P = 0.030) were significantly associated with drug discontinuation, whereas the class of biologics did not reach statistical significance (HR: 2.11, 95% CI: 0.96-4.63, P = 0.064).</p><p><strong>Conclusion: </strong>In patients with AS who had prior experience with biologics, the drug retention of TNF inhibitors tended to be higher compared to IL-17 inhibitors in real-world clinical practice. However, the factors significantly associated with higher drug survival were a lower number of previously exposed biologics and a lower BASDAI.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"27 1","pages":"135"},"PeriodicalIF":4.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFNγ production during cell interactions distinguishes localized from diffuse pigmented villonodular synovitis and rheumatoid arthritis.","authors":"Mélissa Noack, Pierre Miossec","doi":"10.1186/s13075-025-03590-z","DOIUrl":"10.1186/s13075-025-03590-z","url":null,"abstract":"<p><strong>Background: </strong>Pigmented villonodular synovitis (PVNS) is a rare articular disease characterized by aggressive synovial proliferation, with localized or diffuse forms. PVNS shares features of an inflammatory disease such as rheumatoid arthritis (RA), including immune cell infiltrate. Thus, we aimed to evaluate PVNS synoviocyte response to inflammatory stimulation or cell interactions to better understand their role in pathophysiology. Results were compared with those in RA.</p><p><strong>Methods: </strong>Synoviocytes were treated with pro-inflammatory cytokines, IL-17 and/or TNF. IL-6 and IL-8 production was evaluated by ELISA in culture supernatants after 48 h. Migratory capacity was evaluated by a cell scraping assay. Peripheral blood mononuclear cells (PBMC) from healthy donors were co-cultured with PVNS or RA synoviocytes during 48 h, in the presence or not of phytohemagglutinin (PHA). Cytokine production (IL-17, IL-6, IFN-γ, IL-10, IL-1β and TNF) was measured by ELISA.</p><p><strong>Results: </strong>The addition of IL-17 and TNF stimulated IL-6 and IL-8 secretion by both PVNS and RA synoviocytes, with similar responses between PVNS and RA synoviocytes. The highest production of IL-6 and IL-8 was obtained with the combination of IL-17 + TNF. Diffuse PVNS synoviocytes were less potent to cover a scratch area than localized PVNS or RA synoviocytes (p < 0.05). Finally, responses to cell interactions were assessed using co-cultures between synoviocytes and activated immune cells. IL-17, IL-6, IFNγ, IL-10, IL-1β and TNF production was measured after 48 h. Cell interactions induced massive cytokine production, mainly in PHA activated condition. The source of stromal cells affected the secretion resulting from these interactions. Localized and diffuse PVNS synoviocytes induced more IL-17 than RA synoviocytes (p ≤ 0.01). Localized PVNS induced more IFNγ than both diffuse PVNS and RA synoviocytes (p ≤ 0.05). IL-10 production was negatively correlated with IFNγ secretion.</p><p><strong>Conclusion: </strong>In conclusion, results show differences in synoviocyte profiles or in response to cell interactions depending on synoviocyte source, with changes in IFNγ / IL-10 balance associated with localized PVNS. These differences could be used to adapt the therapeutic strategy to each form of PVNS.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"27 1","pages":"134"},"PeriodicalIF":4.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-interferon-α antibodies associate with disease activity and prognosis in anti-MDA5-positive dermatomyositis","authors":"Chao Sun, Hongxia Yang, Yingfang Zhang, Shiyu Wu, Xinxin Zhang, Wei Jiang, Qinglin Peng, Guochun Wang, Xin Lu","doi":"10.1186/s13075-025-03600-0","DOIUrl":"https://doi.org/10.1186/s13075-025-03600-0","url":null,"abstract":"Interferons (IFN) are implicated in the pathogenesis of anti-MDA5 dermatomyositis (anti-MDA5-DM), but the presence of anti-IFN antibodies remains unclear. This study aims to assess serum levels of anti-IFN-α antibodies in anti-MDA5-DM patients and explore their clinical associations. Serum samples from 176 anti-MDA5-DM patients and 55 healthy controls were analyzed for anti-IFN-α antibody levels using an in-house ELISA assay, with immunoblot validation in a subset. Associations between anti-IFN-α antibodies and disease activity or prognosis were assessed. The prevalence of anti-IFN-α antibodies in anti-MDA5-DM patients was 17.6% (31/176), with higher rates in those aged over 60 years. Anti-IFN-α antibody-positive patients exhibited significantly higher incidences of RP-ILD (67.7% vs. 41.4%, p = 0.008) and pulmonary infections (74.2% vs. 46.2%, p = 0.005), with fungi, particularly Aspergillus, being the predominant pathogens. Serum anti-IFN-α antibody levels positively correlated with IgG (r = 0.48, p < 0.0001), ESR (r = 0.28, p = 0.003), ferritin (r = 0.16, p = 0.03), lung VAS (r = 0.24, p = 0.01), and PhGA VAS (r = 0.28, p = 0.002). Longitudinal analysis showed that changes in anti-IFN-α antibody levels paralleled changes in skin VAS, lung VAS, and PhGA VAS (p = 0.015, 0.005, and 0.004, respectively). Notably, treatment-aggravated cases had increased anti-IFN-α antibody levels from baseline (p = 0.017), while remission cases showed decreased levels (p = 0.004). Mortality was significantly higher in anti-IFN-α positive patients (Log-rank p = 0.006). A subset of anti-MDA5-DM patients demonstrated positive serum anti-IFN-α antibodies. The significant association of these antibodies with disease activity and prognosis suggests their potential as a clinical biomarker. Monitoring anti-IFN-α antibody levels may provide an effective means to assess treatment response and predict outcomes in anti-MDA5-DM.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"41 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533882","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":"Risk factors affecting the vital prognosis in patients with rheumatoid arthritis after primary cervical spine surgery: a retrospective study","authors":"Takafumi Kuramoto, Koji Sakuraba, Kazuhiro Kai, Kazumasa Terada, Nobuo Kobara, Hirofumi Bekki, Jun-ichi Fukushi","doi":"10.1186/s13075-025-03593-w","DOIUrl":"https://doi.org/10.1186/s13075-025-03593-w","url":null,"abstract":"The effect of biologics on cervical spine lesions (CSLs) and vital prognosis in patients with rheumatoid arthritis (RA) remains unclear. This study investigated the risk factors for a poor vital prognosis in patients with RA requiring primary cervical spine surgery for CSLs. We retrospectively investigated 139 patients with RA who underwent primary cervical spine surgery between January 2001 and December 2020. The vital prognosis was calculated using the Kaplan–Meier method. Patient data were collected from medical records to analyse the risk factors for vital prognosis using univariate and multivariate Cox regression analyses. The vital prognosis was 62.7% at 10 years according to the Kaplan–Meier method. In univariate analysis, advanced age, lower serum albumin levels, high-dose prednisolone administration, non-use of methotrexate, and subaxial subluxation (SAS) comorbidity were significantly associated with a high risk of mortality. In multivariate analysis, advanced age, lower serum albumin levels, high-dose prednisolone administration, and SAS comorbidity were identified as risk factors for a poor vital prognosis. SAS comorbidity, high-dose prednisolone administration, lower serum albumin levels, and advanced age exacerbate the vital prognosis in patients with RA requiring primary cervical spine surgery. Strict disease control aimed at preventing CSL progression to SAS by maintaining the nutritional status and without using steroids is necessary to improve the vital prognosis of patients with RA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"19 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521201","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":"Semaphorin4B is elevated in rheumatoid arthritis and enhances the inflammatory phenotype of macrophages and fibroblast-like synoviocytes","authors":"Sara Martínez-Ramos, Carlos Rafael-Vidal, Jaime Marty, Beatriz Malvar-Fernández, Coral Mouriño, Nair Pérez, Irene Altabás, Francisco J. Maceiras Pan, David Fernández-Fernández, Carmen Conde, Megan M. Hanlon, Conor M. Smith, Paul Peter Tak, Douglas J. Veale, Ursula Fearon, Jose María Pego-Reigosa, Samuel García","doi":"10.1186/s13075-025-03592-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03592-x","url":null,"abstract":"Several members of the class 4 semaphorins are involved in the pathogenesis of rheumatoid arthritis (RA), regulating proinflammatory functions, but the role of (Sema)phorin4B remains unexplored. Therefore, the aim of this study was to determine the expression and function of Sema4B in RA. Peripheral blood monocytes from healthy controls (HC) and patients with RA were differentiated into M1 macrophages and stimulated with Sema4B and LPS alone and in combination. Fibroblast-like synoviocytes (FLS) from patients with osteoarthritis (OA) and RA and 3D synovium micromasses, formed by RA FLS and RA monocytes, were stimulated with Sema4B and TNF-α alone and in combination. PlexinB2 expression was knocked down using siRNA. Synovial mRNA expression was obtained from gene expression array in GEO-NCBI and determined by (q)uantitative PCR. Protein expression was determined by immunohistochemistry, immunoblotting and ELISA. FLS viability, invasion and migration were determined using calcein, invasion and wound repair scratch assays, respectively. The expression of Sema4B was higher in the synovial tissue of patients with RA, as well as in RA FLS compared to OA FLS. Importantly, the stimulation of RA FLS and RA MØ with inflammatory mediators induced the expression of Sema4B. Functionally, Sema4B alone induced FLS migration and invasion, and enhanced the TNF-α or LPS-induced production of inflammatory mediators (Interleukin (IL)-6, IL-8, TNF-α, CCL-2) and matrix metalloproteases (MMP-1 and MMP-3) in RA FLS, RA MØ and the 3D synovium model. In RA FLS, this effect was mediated by the receptor PlexinB2. In an inflammatory context, Sema4B induces an aggressive FLS phenotype and the production of pro-inflammatory mediators by FLS and MØ. These results suggest that Sema4B is involved in the pathogenic processes observed within the RA synovium.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"653 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521045","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":"Targeting neutrophil-driven inflammation in adult-onset still’s disease: molecular insights from gene expression profiles","authors":"In-Woon Baek, Hyoun-Ah Kim, Kyung-Su Park, Ki-Jo Kim","doi":"10.1186/s13075-025-03598-5","DOIUrl":"https://doi.org/10.1186/s13075-025-03598-5","url":null,"abstract":"The rarity and heterogeneity of adult-onset Still’s disease (AOSD) pose significant challenges in understanding its precise pathogenic mechanisms, developing effective treatment options, and establishing therapeutic strategies. A comprehensive analysis of gene expression profiles could help to bridge the knowledge gaps in those areas. A blood transcriptomic dataset comprising 31 patients with AOSD and 22 healthy controls was fetched. Cellular and molecular features were identified by analyzing differentially expressed genes (DEGs) and functional enrichment. Optimal molecular targets for neutrophil activation were identified using kernel-based diffusion scoring techniques. Blood molecular signatures indicate that neutrophil degranulation is the most enriched pathological process in AOSD. Neutrophil degranulation correlated significantly with the expression of Fcγ receptors, IL-1 receptors, and chemokine receptors and their signaling activities. IL-1 inhibitors and IL-6 inhibitors did not exhibit a diffusion score favorable for directly deactivating neutrophil degranulation, but agents targeting CXCR1/CXCR2, C5AR1, neutrophil elastase, SRC, and SYK demonstrated significant diffusion scores for neutrophil degranulation. In particular, CXCR1, CXCR2, and C5AR1 were the DEGs predominantly expressed in neutrophils and closely associated with neutrophil degranulation in a context-specific functional analysis. Neutrophil activation is a key pathological module in AOSD. Therapeutic approaches aimed at neutrophils could offer a promising opportunity to regulate the inflammatory response in AOSD.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"19 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521043","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":"Decoding the impact of exercise and αCGRP signaling on murine post-traumatic osteoarthritis progression","authors":"Patrick Pann, Paul Kalke, Verena Maier, Nicole Schäfer, Hauke Clausen-Schaumann, Arndt F. Schilling, Susanne Grässel","doi":"10.1186/s13075-025-03589-6","DOIUrl":"https://doi.org/10.1186/s13075-025-03589-6","url":null,"abstract":"Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage breakdown, subchondral bone remodeling, and inflammation. Mechanical stress, such as exercise, can influence OA progression, acting as either a therapeutic intervention or a risk factor depending on intensity. The sensory neuropeptide αCGRP plays a role in modulating cartilage, bone, and inflammatory responses, making it a potential mediator of exercise effects on OA. This study investigated the impact of αCGRP deficiency and exercise intensity on OA progression in a post-traumatic murine model. OA was induced in male αCGRP knockout (KO) and wild type (C57Bl/6J) mice via destabilization of the medial meniscus (DMM). Mice underwent moderate or intense treadmill exercise for up to 6 weeks (8 weeks post-surgery). Histological analyses were performed to assess cartilage degradation. Subchondral and metaphyseal bone morphology as well as cartilage stiffness were evaluated by nanoCT and atomic force microscopy (AFM), respectively. Serum inflammatory markers were analyzed using multiplex immunoassays. Serum levels of proinflammatory markers were elevated in αCGRP-deficient mice, particularly after intense exercise, independent of OA progression. DMM surgery induced significant cartilage degradation. Gross cartilage morphology was not influenced by exercise intensity or αCGRP deficiency, but αCGRP deficiency prevented articular cartilage extracellular matrix stiffening after DMM and intense exercise. Subchondral bone sclerosis was induced by αCGRP deficiency and DMM but mitigated by intense exercise. In metaphyseal bone, intense exercise induced trabecular loss in αCGRP-deficient mice. This study highlights αCGRP as an intrinsic regulator of joint and bone responses to mechanical loading during OA. While cartilage degradation after DMM and treadmill exercise was unaffected by lack of αCGRP, its deficiency altered ECM stiffness, bone remodeling, and inflammatory responses. These findings position αCGRP as a critical regulator of joint homeostasis, particularly for bone health during running exercise and OA progression.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335020","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":"Global burden and trends of musculoskeletal disorders in postmenopausal elderly women: a 1990–2021 analysis with projections to 2045","authors":"Jianye Tan, Zhenglin Zhu, Xingkuan Wang, Bingsheng Yang, Senrui Liu, Meiling Shi, Yujia Luo, Chengcheng Du, Yinsong Sun, Junyi Liao, Yiting Lei, Wei Huang","doi":"10.1186/s13075-025-03587-8","DOIUrl":"https://doi.org/10.1186/s13075-025-03587-8","url":null,"abstract":"The global burden and trend of musculoskeletal disorders (MSDs) in postmenopausal women (PMW) remain unclear. Using the Global Burden of Disease (GBD) 2021 data, this study assessed the prevalence and disability-adjusted life years (DALYs) for rheumatoid arthritis (RA), osteoarthritis (OA), low back pain (LBP), neck pain (NP), gout, and other musculoskeletal conditions (OMSKDs) from 1990 to 2021. Bayesian Age-Period-Cohort (BAPC) models projected trends to 2045. Health inequalities were analyzed using the Slope Index of Inequality (SII) and the Concentration Index, with decomposition methods identifying the drivers of burden changes. From 1990 to 2021, the age-standardized prevalence and DALYs rates have significantly increased among PMW, with OA and LBP being the primary contributors to this burden. These increases were primarily driven by population growth. Specifically, RA, OA, and gout accounted for more than 50% of the total burden in women across all age groups, with RA burden being 1.2 times higher than that in premenopausal women, OA 3.1 times higher, and gout 2.9 times higher. Notably, in PMW, the burden of gout was 74%. The burden of gout is strongly correlated with the Socio-Demographic Index (SDI), particularly in high-income regions, such as North America, where the United States exhibits the highest DALYs rates. Furthermore, projections indicate that by 2045, the global burden of MSDs could double, with OA potentially affecting nearly 50% of the PMW. From 1990 to 2021, the global burden of MSDs among PMW has risen significantly, with notable regional disparities underscoring the critical need for tailored preventive strategies to alleviate the worldwide impact of these conditions.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"240 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320203","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":"RTA 408 attenuates TBHP-Induced apoptosis in nucleus pulposus cells via Nrf2/ARE and NF-κB signaling pathways: in vitro and in vivo evidence for mitigating rats’ intervertebral disc degeneration","authors":"Weibin Chen, Defang Li, Lihan Chen, Jichang Fei, Mengxuan Bian, Qingmin Zeng, Zengxin Jiang, Jingping Wu","doi":"10.1186/s13075-025-03588-7","DOIUrl":"https://doi.org/10.1186/s13075-025-03588-7","url":null,"abstract":"Intervertebral disc degeneration (IDD) is a leading cause of spinal disorders, driven by oxidative stress-induced nucleus pulposus cell (NPC) apoptosis and extracellular matrix (ECM) degradation. Nuclear factor erythroid 2-related factor 2 (Nrf2) activators hold therapeutic promise due to their antioxidative properties. This study investigates the efficacy of RTA 408, a synthetic Nrf2-activating terpenoid, in mitigating oxidative damage and IDD progression. In vitro, tert-butyl hydroperoxide (TBHP)-treated rat NPCs were pretreated with RTA 408 (10–100 nM) to assess antioxidative and antiapoptotic effects via CCK-8, ROS/DCFH-DA, MDA/SOD assays, Annexin V-FITC/PI staining, and mitochondrial membrane potential (JC-1) analysis. Western blotting evaluated Nrf2/ARE, NF-κB pathways, and ECM regulators (MMPs, ADAMTS5, collagen II, aggrecan). In vivo, a rat IDD model was established via coccygeal disc puncture, with RTA 408 (200/500 µg/kg, intraperitoneal) administered weekly. MRI, histopathology (H&E, Safranin O), and immunohistochemistry (aggrecan, MMP13, Nrf2) assessed disc degeneration over 4–8 weeks. In vitro, RTA 408 restored NPC viability, reduced ROS and MDA levels, and elevated SOD activity after TBHP exposure. It inhibited apoptosis (lower cleaved caspase-3 and BAX expression; higher BCL-2 levels) and mitochondrial depolarization. RTA 408 activated the Keap1/Nrf2/ARE pathway (promoted Nrf2 nuclear translocation and upregulated HO-1/NQO1) while suppressing NF-κB signaling (reduced phosphorylation of P65 and IκBα). ECM degradation was reversed (downregulated MMP3/9/13 and ADAMTS5; upregulated collagen II and aggrecan). In vivo, RTA 408 preserved disc structure, decreased Pfirrmann scores, and improved MRI indices (enhanced T2 signal intensity). Histopathological analysis confirmed reduced ECM loss and annulus fibrosus disruption, correlating with elevated Nrf2 expression and diminished MMP13 levels in nucleus pulposus. High-dose RTA 408 showed stronger therapeutic effects than low-dose treatment. RTA 408 mitigates oxidative stress-induced NPC apoptosis and ECM degradation via dual modulation of Nrf2/ARE activation and NF-κB suppression. Systemic administration of RTA 408 delays IDD progression in vivo, highlighting its therapeutic potential for degenerative spinal disorders. These findings support further clinical exploration of RTA 408 as a novel Nrf2-targeted therapy for IDD.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"44 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319989","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}