Arthritis Research & Therapy最新文献

{"title":"Mortality in polymyalgia rheumatica: a 38-year prospective population-based cohort study from Southern Norway","authors":"Stig Tengesdal, Øyvind Molberg, Øyvind Holme, Jan Tore Gran, Geirmund Myklebust","doi":"10.1186/s13075-025-03613-9","DOIUrl":"https://doi.org/10.1186/s13075-025-03613-9","url":null,"abstract":"Robust long-term mortality data on patients with polymyalgia rheumatica (PMR) are lacking. The aim of this study was to determine all-cause mortality in isolated PMR using a large, population-based, inception cohort followed prospectively over a 38-year period. Between 1987 and 1997, 337 incident cases of PMR and biopsy-proven GCA were included in a prospective, population-based inception cohort in Aust-Agder County, Norway. Diagnosis was ascertained clinically by a rheumatologist, with PMR cases meeting Bird`s criteria. Patients were followed until death or end of study on December 31st, 2024. Each case was matched by gender, age at inclusion, and residency with 15 population comparators drawn from the population registry in Norway. We assessed mortality and survival by standard mortality ratios (SMR) and the Kaplan-Meier method. A total of 274 patients with isolated PMR (66.1% female, mean age at diagnosis 71.9 years) and 63 patients with GCA (76.2% female, mean age at diagnosis 71.6 years) were included. By the end of the study, 96.4% of all patients were deceased. Mean follow-up time for all patients was 13.7 years, with a maximum of 35.3 years. For cases with isolated PMR, the overall SMR was 0.97 (95% confidence interval [CI] 0.85, 1.09), for men 0.77 (95% CI 0.62, 0.95), and for women 1.11 (95% CI 0.95, 1.28). For GCA, the overall SMR was 1.10 (95% CI 0.85, 1.40), with no gender difference. In this comprehensive long-term follow-up study with nearly complete data on mortality, isolated PMR was not associated with increased mortality, reinforcing the view that it does not confer a higher mortality risk.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"5 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669632","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":"Meta-analysis identifies the major impact of patient classification on the ACPA association with rheumatoid arthritis-associated interstitial lung disease (RA-ILD)","authors":"Bartosz Kaczmarczyk, Carmen Conde, Antonio Gonzalez","doi":"10.1186/s13075-025-03617-5","DOIUrl":"https://doi.org/10.1186/s13075-025-03617-5","url":null,"abstract":"We need screening for RA patients at high risk of RA-ILD to prevent the associated decrease in life quality and survival. The proposed screenings disagree regarding the anti-citrullinated protein antibodies (ACPA) because of their inconsistent association across recent studies. Therefore, we hypothesized that meta-analysis of the published reports should reveal clues explaining the heterogeneity of results, helping us progress in RA-ILD early detection. We aimed to discover the factors accounting for the variability of the ACPA association in the published reports. We searched the Web of Science and PubMed databases for studies reporting ACPA in RA-ILD and RA-control groups. The identified studies were analyzed using meta-analysis and meta-regression to identify moderators of the ACPA association. We found 513 unique records, containing 31 eligible data sets. The meta-analysis preceding the search for moderators showed a remarkable heterogeneity (pQ = 5.7 × 10–7). Appropriate tests showed that it was largely attributable (58.1%) to an outlier study, which had recruited cases and controls in different place and time contexts. The exclusion of this outlier from subsequent analyses did not completely remove heterogeneity (pQ = 0.004). However, it permitted the identification of the patient classification method as a significant moderator: The 14 studies using chest CT showed stronger ACPA association with RA-ILD (OR = 3.05 [95%CI: 2.12–4.38]) than the 16 employing multifactorial criteria (1.55 [95%CI: 1.18–2.03]; p = 0.0047 for the contrast). This moderator accounted for the significant heterogeneity (pQ = 0.079), was robust in sensitivity analyses, and was the only one found. Our results validate the ACPA association with RA-ILD, reinforce the importance of study design, and suggest the need to consider if studies relying on chest CT for classification could be more fruitful in the search for RA-ILD biomarkers.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"24 1","pages":"151"},"PeriodicalIF":4.9,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664425","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":"Early-onset difficult-to-treat rheumatoid arthritis: proposal of data-driven predictors and temporal threshold","authors":"Pablo Rodriguez-Merlos, Jose Luis Cabrera-Alarcón, Virginia Ruiz-Esquide, Chafik Alejandro Chacur, Raimon Sanmartí, Eugenio De Miguel-Mendieta, Jose María Álvaro-Gracia, Alejandro Balsa, Chamaida Plasencia-Rodríguez, Marta Novella-Navarro","doi":"10.1186/s13075-025-03621-9","DOIUrl":"https://doi.org/10.1186/s13075-025-03621-9","url":null,"abstract":"While risk factors for difficult-to-treat rheumatoid arthritis (D2TRA) have been studied in recent years, no studies have determined if there are differences between early and late developers of D2TRA. This study investigates whether patients can be classified by time to D2TRA development and examines risk factors for earlier onset. Observational study involving D2TRA patients whose reason for switching b/tsDMARD therapy was inefficacy (D2TRA-Inneficacy). Demographic data, comorbidities and disease characteristics, acute phase reactants and Disease Activity Score-28 [DAS28-ESR]) at baseline and 6 months after initiation of the first b/tsDMARD, and duration of each treatment were recorded. Using LASSO (Least Absolute Shrinkage and Selection Operator) Cox-regression feature-selection strategy, we identified those factors influencing the time to D2TRA-Inneficacy. DBSCAN clustering was conducted to identify subgroups based on time to D2TRA. Finally, we used ROC and Precision-Recall curves in tandem with the Youden index to establish a cutoff point for differentiating early and late-D2TRA. Of the 131 patients with D2TRA, 96 (72.7%) were classified as D2TRA-inefficacy. The variables presence of anxiety-depressive syndrome (ADS) at first b/tsDMARD, CRP at 6 months after starting the first b/tsDMARD and age at disease diagnosis were selected based on their contracted scores from the LASSO Cox-regression model, following the criterion of minimizing the cross-validated error. DBSCAN clustering based on selected variables identified three clusters. These clusters, differentiated by time to D2TRA, classified patients into early and late D2TRA groups. Finally, an optimal cut-off point of 44.5 months was determined using the Youden index to distinguish between the two groups. In our cohort, the cut-off time for defining early developers of D2TRA-inefficacy was 44.5 months. The presence of ADS diagnosis, a higher CRP 6 months after the first b/tsDMARD, and being older at diagnosis were predictors of early development of D2TRA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"109 1","pages":"153"},"PeriodicalIF":4.9,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664447","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":"Chondrocyte-specific knockout of Piezo1 and Piezo2 protects against post-traumatic osteoarthritis structural damage and pain in mice","authors":"Erica V. Ely, Kristin L. Lenz, Sophie G. Paradi, Seth Ack, Abraham Behrmann, Sarah Dunivan, Lauryn Braxton, Wolfgang Liedtke, Yong Chen, Kelsey H. Collins, Farshid Guilak","doi":"10.1186/s13075-025-03620-w","DOIUrl":"https://doi.org/10.1186/s13075-025-03620-w","url":null,"abstract":"Osteoarthritis (OA) is a debilitating joint disease characterized by cartilage degeneration, synovial inflammation, and bone remodeling, with limited therapeutic options targeting the underlying pathophysiology. Mechanosensitive ion channels Piezo1 and Piezo2 play crucial roles in chondrocyte responses to mechanical stress, mediating mechanotransduction pathways that influence chondrocyte survival, matrix production, and inflammatory signaling, but their distinct contributions to OA pathogenesis remain unclear. Using inducible, chondrocyte-specific Aggrecan-Cre (Acan) mice, we investigated Piezo1, Piezo2, and combined Piezo1/2 conditional knockouts (cKOs) using the destabilization of the medial meniscus (DMM) model of post-traumatic OA in male and female mice. Pain and behavioral assessments were conducted at four time points to evaluate OA progression, while cartilage damage, bone remodeling, and synovial inflammation were assessed at the final endpoint of 28 weeks. Statistical analyses included one-way and two-way ANOVA with Tukey’s multiple comparison test. Piezo1 cKO delayed pain onset but ultimately exacerbated cartilage degradation and synovitis, emphasizing its dual role in protective and pathogenic mechanotransduction. While the Piezo2 cKO reduced pain and preserved activity, it failed to protect cartilage. Notably, Piezo1/2 cKO provided the greatest protection against cartilage degeneration, synovitis, and pain. Micro-computed tomography analyses revealed that Piezo2 is critical for maintaining trabecular bone integrity, with a Piezo2 cKO leading to decreased bone volume, thickness, and density, independent of injury. Piezo2 cKO also reduced normal meniscal ossification that occurs with age in mice. In contrast, a Piezo1/2 cKO normalized most bone remodeling parameters observed in Piezo2 cKO mice but did not restore medial tibial plateau thickness, highlighting Piezo2’s essential role in bone structure. These findings demonstrate the overlapping and compensatory roles of Piezo1 and Piezo2 in OA pathogenesis. Dual inhibition of Piezo1 and Piezo2 may offer a novel, effective therapeutic strategy targeting both structural and symptomatic aspects of the disease.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"659 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664443","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":"Disease remission and sustained remission after etanercept biosimilar or originator initiation in rheumatoid arthritis: an interim real-world analysis","authors":"Marina G. Birck, Jessica Boivin, Laura Yan, Nathalie Carrier, Cristiano S. Moura, Walter P. Maksymowych, Gilles Boire, Denis Choquette, Luck Lukusa, Michael Mallinson, Linda Wilhelm, Autumn Neville, Sasha Bernatsky","doi":"10.1186/s13075-025-03607-7","DOIUrl":"https://doi.org/10.1186/s13075-025-03607-7","url":null,"abstract":"We compared time to first remission and prevalence of sustained remission in participants with rheumatoid arthritis (RA) initiating etanercept biosimilar (ETA-B) or originator (ETA-O). We studied etanercept-naive participants with RA from four Canadian prospective cohorts who initiated ETA-B or ETA-O (Jan/2015-May/2022). Disease remission was determined using disease activity scales. Sustained remission was defined as at least two consecutive visits in remission within the first 12 months of follow-up. Multivariate Cox regression was used to compare the probability of achieving remission between ETA-B and ETA-O, and multivariate logistic regression was used to assess sustained remission. We studied 150 participants with RA (ETA-B: 65.3%). Among 125 participants not in remission at baseline, the median time to first remission was 8.7 months (95% confidence intervals [CI] 5.2–12.1) in the ETA-B group and 14.5 months (95% CI 4.7–18.6) in the ETA-O group. Time to first remission was similar between the groups (log-rank test: P-value = 0.51). Multivariate Cox regression showed no clear difference in first remission between ETA-B and ETA-O (adjusted hazard ratio 1.52, 95% CI 0.68–3.39). Among 125 participants with at least 12 months of follow-up, the prevalence of sustained remission was 19.5% for ETA-B and 21.0% for ETA-O. In multivariate analysis, we did not detect a significant difference in sustained remission between ETA-B and ETA-O (adjusted odds ratio 1.14, 95% CI 0.29–4.87). We did not detect clear differences in first remission and sustained remission between participants with RA initiating ETA-B or ETA-O. Not applicable.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"153 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652089","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":"Entheseal Doppler signals in ultrasound are associated with vasodilator drugs and age in patients with radiographic axial spondyloarthritis","authors":"Magnus Hallström, Anna Deminger, Caroline Feldthusen, Erik Hulander, Mats Geijer, Eva Klingberg, Helena Forsblad-d’Elia","doi":"10.1186/s13075-025-03614-8","DOIUrl":"https://doi.org/10.1186/s13075-025-03614-8","url":null,"abstract":"The ability of modern ultrasound machines to detect signs of enthesitis has increased, yet there is a lack of studies on patients with long-standing radiographic axial spondyloarthritis (r-axSpA). Hence, we aimed to investigate the prevalence and clinical significance of Doppler signals indicative of inflammation in peripheral entheses of patients with long-standing disease. Patients fulfilling the modified New York criteria for ankylosing spondylitis were included in this cohort study. Peripheral entheses were examined clinically and the presence of focal pain was self-reported on a mannequin. Ultrasound examination of 1692 entheses was performed. Doppler signals were graded from 0 to 3 using color Doppler ultrasound and Smooth Microvascular Imaging. Multivariable linear regression was used to explore factors influencing Doppler signals. One hundred and forty-one patients were included with, age (mean (SD)) 60 (12) years, symptom duration 34 (12) years, males 57%, and HLA-B27 86%. Overall, 21.3% of patients presented with ≥ 1 active ultrasound enthesitis (Doppler signals combined with hypoechoic tissue). In 4.3% of patients these findings were tender on palpation. Isolated Doppler signals were found in 89.4–97.1% of patients, with the highest mean Doppler grades in the triceps entheses (0.88), and the lowest in the Achilles tendons (0.28). In multivariable linear regression analysis, age (B (95% CI)) (0.01 (0.00; 0.01), p = 0.004), daily NSAIDs (0.15 (0.00; 0.30), p = 0.048), vasodilator drugs 0.16 (0.01; 0.32, p = 0.041), but not AS disease activity score, were associated with total Doppler scores. The prevalence of asymptomatic entheseal ultrasound Doppler findings was overall high. The use of vasodilator drugs and higher age increased the Doppler scores. No association between disease activity and Doppler scores was found in patients with long-standing disease.\u0000","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"94 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629893","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":"Killing arthritogenic fibroblast-like synoviocytes: an example using cytotoxic aptamers binding nucleolin","authors":"George D. Kalliolias, Efthimia K. Basdra, Athanasios G. Papavassiliou","doi":"10.1186/s13075-025-03618-4","DOIUrl":"https://doi.org/10.1186/s13075-025-03618-4","url":null,"abstract":"“Pauci-immune” and “fibroblast-rich” synovial pathotypes are predictors of resistance to multi-drug immunosuppression. For these “difficult-to-treat” (D2T) endotypes of rheumatoid arthritis (RA), depletion of arthritogenic fibroblast-like synoviocytes (FLS) has emerged as promising treatment strategy. Profiling at a single-cell level has enabled the molecular characterization of distinct subpopulations of arthritogenic FLS. Advances in molecular engineering have empowered the development of multiple modalities (anti-FLS antibodies, T-cell engagers, cytotoxic cells with chimeric receptors recognizing FLS-specific antigens) to achieve depletion of arthritogenic subpopulations of FLS with unprecedented selectivity. A recently published study highlighted in this article, adds apoptosis-promoting aptamers in the armamentarium of the FLS-killing pipeline.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"199 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622196","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":"Identification of serum exosome proteins in systemic sclerosis with interstitial lung disease by aptamer proteomics","authors":"Sonsoles Piera-Velazquez, Simon T. Dillon, Xuesong Gu, Towia A. Libermann, Sergio A. Jimenez","doi":"10.1186/s13075-025-03595-8","DOIUrl":"https://doi.org/10.1186/s13075-025-03595-8","url":null,"abstract":"A major unmet need for Systemic Sclerosis (SSc) clinical management is the absence of well validated biomarkers for early diagnosis of SSc-associated interstitial lung disease (SSc-ILD). The objective of this study was to identify proteins contained within serum exosomes that may serve as potential biomarkers to differentiate patients with Diffuse SSc without SSc-ILD from patients with Diffuse SSc with SSc-ILD employing aptamer-based proteomics. Serum exosomes were isolated from two cohorts of patients. The first cohort included 15 patients with Diffuse SSc without SSc-ILD and 14 patients with Diffuse SSc with SSc-ILD and the second cohort included 12 patients with Diffuse SSc with SSc-ILD and 12 patients with Diffuse SSc without SSc-ILD. SOMAscan aptamer proteomics was performed with the first cohort and quantified the concentration levels of 1,305 proteins. Significant associations of differentially elevated or reduced proteins (p < 0.05 |FC|>1.2) discriminating between the two SSc clinical subsets were assessed. Validation of the results obtained from the proteomics analysis of the first cohort was performed with the second cohort. The aptamer proteomic analysis identified 29 proteins increased and 9 proteins decreased in SSc with SSc-ILD as compared to SSc without SSc-ILD. Principal component analysis using the 20 most significantly differentially expressed proteins resulted in excellent separation of the two SSc clinical subsets. Most of the differentially increased proteins converged around enhanced inflammatory responses, immune cell activation, cell death, and abnormal vascular functions and several of them displayed a highly significant correlation with the CO Diffusion Capacity Levels. Aptamer proteomic analysis of circulating exosomes from patients with Diffuse SSc with and without SSc-ILD identified several biologically plausible biomarkers that may be of value to differentiate these two SSc clinical subsets.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"21 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594243","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":"nCD64 index as a new early predictive biomarker for macrophage activation syndrome in adult-onset still’s disease","authors":"Tongxin Wu, Liyang Gu, Bisheng Shi, Yiwei Wu, Jinming Yang, Zhengting He, Xi He, Xinyun Zhu, Liangjing Lu, Xiaoxiang Chen, Ruru Guo","doi":"10.1186/s13075-025-03611-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03611-x","url":null,"abstract":"Macrophage activation syndrome (MAS) represents a severe and potentially life-threatening complication of adult-onset Still’s disease (AOSD), necessitating the identification of sensitive and specific biomarkers for early diagnosis. Our study found significantly elevated CD64 mRNA expression in neutrophils of AOSD patients compared to healthy controls (p = 0.029). The neutrophil CD64 index (nCD64 index) positively correlated with key clinical manifestations, including splenomegaly, sore throat, pulmonary infiltrates, and pericarditis. Effective treatments led to a rapid and significant decrease in the nCD64 index (p < 0.001). Logistic regression showed that an elevated nCD64 index is a risk factor for MAS (OR = 1.073, p = 0.003). ROC curve analysis indicated that the nCD64 index reliably distinguished AOSD patients with MAS (AUC = 0.877; cutoff = 32.09; p < 0.001) and combined utilization of nCD64 index, ferritin, and sIL-2R demonstrated a strong predictive value. Correlations with hospitalization length (r = 0.382, p < 0.001) and maximum glucocorticoid dose (r = 0.326, p = 0.003) were also observed. Kaplan-Meier analysis revealed a significantly higher cumulative incidence of MAS in patients with an nCD64 index > 32.09 (p < 0.001). These findings suggest the nCD64 index is a promising biomarker for early identifying AOSD patients at risk of MAS, aiding in timely diagnosis and management.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"21 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of JAK-STAT signaling and granulocyte–macrophage colony-stimulating factor in the development of osteitis and bone microstructure changes in rheumatoid arthritis","authors":"Tsuneyasu Yoshida, Yoshiki Murotani, Koichi Murata, Hirohiko Imai, Takeshi Iwasaki, Yoichi Nakayama, Masao Katsushima, Mirei Shirakashi, Ran Nakashima, Ryu Watanabe, Kosaku Murakami, Hajime Yoshifuji, Akio Morinobu, Motomu Hashimoto","doi":"10.1186/s13075-025-03597-6","DOIUrl":"https://doi.org/10.1186/s13075-025-03597-6","url":null,"abstract":"Osteitis on magnetic resonance imaging (MRI) and bone microstructure changes (BMC) on high-resolution peripheral quantitative computed tomography (CT) are the earliest signs of arthritis, preceding the development of bone erosion on X-ray in rheumatoid arthritis (RA). Recently, a Janus kinase (JAK) inhibitor, baricitinib, reportedly suppresses these early changes. This study aimed to elucidate the underlying molecular mechanism of osteitis and BMC using an animal model of RA and human samples. Osteitis and BMCs were assessed via MRI and micro-CT, respectively, in zymosan-treated SKG mice. Bone marrow (BM) cells were analysed via flow cytometry. JAK‒signal transducer and activator of transcription (STAT) cytokine expression was measured via performing quantitative PCR. Zymosan-treated SKG mice received baricitinib, anti-granulocyte‒macrophage colony-stimulating factor (GM-CSF) antibodies, or recombinant GM-CSF (r-GM-CSF). r-GM-CSF was also used in an in vitro osteoclast differentiation assay. Osteoclast differentiation was also investigated with human monocytes. Osteitis and BMCs occurred prior to arthritis in SKG mice. Granulocyte‒macrophage-lineage cells and osteoclast precursor cells (OCPs) expanded in the inflammatory BM. Receptor activator of nuclear factor kappa-B ligand-positive osteoclasts were observed at BMC sites. The expression of GM-CSF, a JAK‒STAT cytokine, was upregulated in osteitic BM. Both baricitinib and anti-GM-CSF antibodies suppressed osteitis and BMCs, whereas r-GM-CSF exacerbated these changes. In vitro addition of r-GM-CSF to osteoclast differentiation assay markedly increased the number and size of osteoclasts, especially when added in the late phase of osteoclast differentiation both in mice and humans. GM-CSF drives osteitis and BMCs by increasing granulocyte‒macrophage-lineage cells and OCPs and promoting osteoclast differentiation. Targeting GM-CSF is a potential therapeutic strategy to prevent early radiographic changes in RA. ","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"13 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594245","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}