Arthritis Research & Therapy最新文献

{"title":"KLF11 alleviates rheumatoid arthritis by regulating M1 macrophage polarization via downregulation of YAP1 expression","authors":"Xiaodan Liu, Fang Fang, Hongmei Duan, Chunling Wu, Haina Liu, Shuang Ding","doi":"10.1186/s13075-025-03634-4","DOIUrl":"https://doi.org/10.1186/s13075-025-03634-4","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic autoimmune disease, primarily impacting joints and bones. The Gene Expression Omnibus (GEO) datasets (GSE55235 and GSE10500) revealed that KLF11 expression was lower in the patients with RA, which was confirmed by the collected RA samples. However, KLF11's function and molecular mechanism in RA remain to be elucidated. In our study, we investigated this issue using in vivo and in vitro models. Our findings consistently demonstrated the downregulation of KLF11 in mice with collagen-induced arthritis (CIA). Overexpression of KLF11 reduced the arthritis severity and the extent of bone destruction in mice with CIA, whereas KLF11 knockdown exerted the opposite effect. Additionally, it was noted to inhibit M1 macrophage polarization and the ERK pathway both in vivo and in vitro. The JASPAR database indicated the potential for KLF11 to bind to the YAP1 promoter region. ChIP and dual-luciferase reporter assays confirmed the binding of KLF11 to the promoter of YAP1. Further experiments demonstrated that KLF11 negatively regulated YAP1 expression in THP-1 cells. YAP1 overexpression partially reversed the KLF11's inhibitory effect on the ERK signaling pathway and M1 macrophage polarization in vitro. KLF11 may be a promising therapeutic target for RA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"82 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of exercise-induced pulmonary hypertension with nailfold capillary density in systemic sclerosis: a single-center retrospective observational study","authors":"Katsuhide Kusaka, Satoshi Kubo, Shingo Nakayamada, Ippei Miyagawa, Yusuke Miyazaki, Yurie Kanda, Yasuyuki Todoroki, Masanobu Ueno, Ryuichiro Kanda, Koshi Setoyama, Masaharu Kataoka, Yoshiya Tanaka","doi":"10.1186/s13075-025-03633-5","DOIUrl":"https://doi.org/10.1186/s13075-025-03633-5","url":null,"abstract":"Exercise-induced pulmonary hypertension (exercise PH) is instrumental in the early detection of pulmonary arterial hypertension. However, the prevalence and specific characteristics of exercise PH in systemic sclerosis (SSc), as well as factors that might facilitate its identification, remain inadequately understood. We investigated the clinical profiles of SSc patients diagnosed as PH, exercise PH, or non-PH. This study included 50 patients with SSc and exercise intolerance. We compared the physical examination findings, biochemistry tests, echocardiography, respiratory function tests, and resting and exercise right heart catheterization outcomes of the PH, exercise PH, or non-PH groups. In a cohort of 50 patients with SSc and exercise intolerance, 30.0% were diagnosed with PH, and 44.0% exhibited exercise PH. Symptoms such as exertional dyspnea and palpitations were more prevalent in the exercise PH group compared to the non-PH group. Furthermore, a lower nailfold capillary density was observed in the exericse PH group. However, there was no difference between the two groups in terms of NT-proBNP level, serum uric acid, inflammatory findings, %DLco%, FVC/%DLco ratio, six-minute walking distance, or peak tricuspid regurgitant velocity. exercise PH was detected in 87.5% of patients presented all with exertional dyspnoea, exertional palpitations, and capillary density ≤ 7/mm. In many patients within the exercise PH group, the pulmonary artery wedge pressure/cardiac output slope exceeded 2 mmHg/L/min, indicating latent heart failure with preserved ejection fraction (HFpEF). In our study, 44.0% of patients with SSc and exercise intolerance exhibited exercise PH, with many potentially having HFpEF. Decreased nailfold capillary density, exertional dyspnea, and palpitations were indicative markers useful for exercise PH screening. exercise PH was present in 44.0% of patients with SSc and exercise intolerance. Most of SSc patients with exercise PH may have had HFpEF. exercise PH was found in 87.5% of SSc patients with dyspnoea, palpitations, and capillary density ≤ 7.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"15 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899594","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":"Mitochondrial calcium uniporter promotes MSU crystal-induced inflammation through inducing mitochondrial Ca2+ overload and ubiquitination of SIRT5 protein","authors":"Qingqing Yu, Renjie Li, Guizhao Yang, Yan Xiao, Xingyu Liu, Yaxin Deng, Xiongyan Luo, Qian Dai, Mei Zeng","doi":"10.1186/s13075-025-03627-3","DOIUrl":"https://doi.org/10.1186/s13075-025-03627-3","url":null,"abstract":"The mitochondrial calcium uniporter (MCU) is the key channel regulating mitochondrial calcium (Ca²⁺) uptake. Growing evidence indicates that mitochondrial Ca²⁺ homeostasis plays a pivotal role in regulating immune cell function. However, how MCU contributes to MSU crystal-driven inflammation and its molecular mechanisms are unclear. Using bone marrow-derived macrophages (BMDMs), wild-type (WT, MCU⁺/⁺), and MCU knockout (MCU⁻/⁻) mice, we investigated the role of MCU in MSU crystal-induced inflammation. Co-immunoprecipitation assays were employed to examine interactions among MCU, SIRT5, and TRIM21. MSU crystals stimulation up-regulated MCU expression and triggered mitochondrial Ca²⁺ overload in macrophages. MCU deficiency reduced mitochondrial Ca²⁺ accumulation, ameliorated mitochondrial dysfunction, and suppressed NLRP3 inflammasome activation in BMDMs treated with MSU crystals. Mechanistically, MCU promoted TRIM21 expression, leading to SIRT5 ubiquitination and degradation. Furthermore, MCU facilitated the interaction between TRIM21 and SIRT5, with MSU crystals enhancing this tripartite association. TRIM21 and SIRT5 were identified as key downstream effectors of MCU, mediating MSU crystal-induced inflammatory responses and oxidative stress. In vivo, MCU deficient mice exhibited diminished immune cell infiltration and IL-1β production in MSU crystal-induced peritonitis and arthritis models. Our findings demonstrate that MCU drives mitochondrial Ca²⁺ overload in MSU crystal-induced inflammation and promotes SIRT5 degradation via the TRIM21-SIRT5 signaling axis. These insights highlight MCU as a potential therapeutic target in gouty inflammation.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899551","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":"Brevilin A, a novel LRRC15 inhibitor, exerts potent anti-rheumatoid arthritis effects by inhibiting the LRRC15/STAT3 signaling pathway","authors":"Zhiping Qiao, Qiqi Meng, Bixia Xiao, Yulei Long, Qi Liang, Tao Su","doi":"10.1186/s13075-025-03629-1","DOIUrl":"https://doi.org/10.1186/s13075-025-03629-1","url":null,"abstract":"Leucine-rich repeat-containing 15 (LRRC15) is a transmembrane protein that is highly expressed in the synovium of patients with rheumatoid arthritis (RA). Brevilin A (BrA), an active compound isolated from Centipeda minima, exerts potent anti-inflammatory effects. However, the anti-RA effect of BrA and its underlying mechanism of action of BrA have not been fully elucidated. Transcriptome analysis was performed to explore biomarkers of RA. An lipopolysaccharide (LPS)-induced RAW264.7 macrophage model, a TNF-α-stimulated RA fibroblast-like synoviocytes (RA-FLSs) model, as well as a collagen-induced arthritis (CIA) rat model were used to explore the anti-RA effects of BrA. Moreover, inhibition or overexpression of LRRC15 was performed to explore the role of LRRC15 signaling in the anti-RA effects of BrA. Transcriptome analysis of patients with RA revealed that LRRC15 expression was significantly upregulated in the synovial tissue of RA patients. BrA significantly downregulated the expression of inflammation-related markers in cell models, and inhibited their proliferation and migration; Moreover, it significantly reduced joint swelling and cartilage damage in CIA rats. Further mechanistic studies suggest that inhibition of LRRC15 inhibits cell proliferation and migration; and overexpression of LRRC15 increases the protein levels of STAT3’s downstream metastasis-related markers. Our findings suggest that BrA, a novel LRRC15 inhibitor, has promising anti-RA activity and potently inhibits LRRC15/STAT3 signaling pathway both in vivo and in vitro. This study not only supports the development of BrA as a novel therapeutic agent for RA treatment, but also paves the way for the development of other LRRC15-targeting therapeutic strategies.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"13 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901872","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":"Investigating potential biomarkers associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis using Mendelian randomization and transcriptomic analysis","authors":"Yujia Wang, Zhimin Chen, Kaiqi Huang, Keng Ye, Shiwei He, Yanfang Xu, Hong Chen","doi":"10.1186/s13075-025-03630-8","DOIUrl":"https://doi.org/10.1186/s13075-025-03630-8","url":null,"abstract":"Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disorder characterized by multi-organ involvement. Early identification and accurate diagnosis of AAV is crucial for improving prognosis. However, research on biomarkers associated with AAV is limited. This study aimed to explore novel biomarkers for AAV through transcriptomic data analysis and Mendelian randomization (MR). AAV-related datasets (GSE104948 and GSE108109) were analyzed. Differentially expressed genes (DEGs) between AAV and normal groups were identified in the GSE104948 dataset. MR analysis was then used to investigate the causal relationship between DEGs and AAV. Genes with a significant causal relationship were selected as candidate genes for further analysis. Machine learning algorithms, ROC curve analysis, and expression evaluation were employed to screen for biomarkers. Additionally, artificial neural networks (ANNs) were constructed, enrichment analysis and immune infiltration were performed, a molecular regulatory network was established, and potential drugs were predicted. Finally, immunofluorescence assays validated the significance of these genes in renal biopsies from patients with ANCA-associated glomerulonephritis. PDK4, PSMB10 (IVW, OR > 1, P < 0.05), PPARGC1A, and FN1 (IVW, OR < 1, P < 0.05) were identified as biomarkers. Specifically, PDK4 and PPARGC1A exhibited significant down-regulation in the AAV group compared to the normal group, while FN1 and PSMB10 showed an opposite pattern. The ANN created based on biomarkers exhibited a robust predictive capacity for assessing the risk of AAV. Furthermore, co-enrichment of PDK4 and PPARGC1A was observed in ‘butanoate metabolism’, and ‘fatty acid metabolism’. Meanwhile, there was a strong positive correlation observed between naive B cells and PDK4, while a substantial negative correlation was found with PSMB10. Molecular regulatory network results demonstrated that XIST exerted regulatory effects on PDK4, FN1, and PPARGC1A through hsa-miR-103a-3p, hsa-miR-1271-5p, and hsa-miR-23a-3p simultaneously. Besides, this study revealed that 19 drugs exhibited potential targeting capabilities towards 4 biomarkers, such as dacarbazine, dichloroacetate, and bortezomib. Validation in renal biopsies from patients with ANCA-associated glomerulonephritis confirmed decreased glomerular expression of PDK4 and PPARGC1A, and increased expression of FN1 and PSMB10 compared to controls. PDK4, PPARGC1A, FN1, and PSMB10 were identified as biomarkers causally related to AAV, offering potential for both precise diagnosis and targeted treatment strategies. ","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"28 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901873","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":"Analysis of epigenetic biomarkers for diagnosis and assessment of severity in rheumatoid arthritis: a cross-sectional study","authors":"Arkaitz Mucientes, Gracia María Martín Núñez, Natalia Mena-Vázquez, Jose Manuel Lisbona-Montañez, Sara Manrique-Arija, Andrés González-Jiménez, Patricia Ruiz-Limón, Aimara Garcia-Studer, Fernando Ortiz-Márquez, Laura Cano-García, Antonio Fernández-Nebro","doi":"10.1186/s13075-025-03628-2","DOIUrl":"https://doi.org/10.1186/s13075-025-03628-2","url":null,"abstract":"Rheumatoid arthritis (RA) is an autoimmune disease influenced by genetic, environmental, and epigenetic factors. Epigenetic modifications, particularly DNA methylation, in immune-related genes may impact inflammation and immune responses. This study aims to analyze methylation patterns in RA patients and controls to identify diagnostic and prognostic epigenetic biomarkers. A cross-sectional study of a prospective cohort comprising 32 patients (16 with severe RA, 16 with nonsevere RA) and 32 healthy controls (discovery cohort) was performed. Severity was defined as a cumulative 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) ≥ 3.2, positive rheumatoid factor (RF) and anti–citrullinated peptide antibody (ACPA) values, and a high Collinsella aerofaciens count (OTU ≥ 0.15). Whole genome methylation analysis was performed using the Infinium Methylation EPIC BeadChip kit. Subsequently, validation by pyrosequencing (PyroMark Q48) was performed for the differentially methylated positions (DMPs) selected both in the discovery cohort and in the remainder of the inception cohort (78 patients and 78 controls). More than half of the participants were women (≥ 75%), and the mean age was 56 years. At whole genome level, an epigenetic signature was associated with both RA and severity of RA. Pyrosequencing confirmed that methylation levels at CpG sites in TBC1D22A, PRHOXNB, ALLC, and PRG2 genes were associated with RA or severity of RA. The novel association between hypermethylation in TBC1D22A and RA was subsequently confirmed in an independent cohort. Our results indicate that the level of DNA methylation in validated DMPs is associated with RA. Thus, these methylation levels are potential biomarkers for the diagnosis, prognosis and severity of RA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797076","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":"Trim21 deficiency alleviates osteoporosis by inhibiting osteoclast differentiation through regulating Txnip","authors":"Ya-Chen Peng, Yong-Sheng Ye, Qin-Xiao Hu, Zhi-Quan Hao, Zhen-Yan Li, Luo-Yong Jiang, Hao-Ran Peng, Ri-Xu Liu, Zhen-Gang Zha, Huan-Tian Zhang","doi":"10.1186/s13075-025-03624-6","DOIUrl":"https://doi.org/10.1186/s13075-025-03624-6","url":null,"abstract":"The tripartite motif containing 21 (Trim21), an E3 ubiquitin ligase, plays a crucial role in the progression of various skeletal diseases, particularly in osteoporosis. In our previous study, Trim21 deficiency was shown to exert dual effects by suppressing bone resorption and enhancing osteogenesis. However, the specific mechanism by which Trim21 inhibits osteoclast (OC) differentiation remains unclear. In this study, we utilized a myeloid cell–specific conditional knockout model of Trim21 to investigate the underlying regulatory mechanisms. OC-specific Trim21 knockout mice were generated and subjected to ovariectomy (OVX) to establish a model of postmenopausal osteoporosis. Bone mass and OC activity were then evaluated using micro-computed tomography (micro-CT) and tartrate-resistant acid phosphatase (TRAP) staining. Bone marrow-derived macrophages (BMMs) were induced to differentiate into OCs, and gene expression levels were detected by qRT-PCR. Additionally, proteomic analysis was performed to identify downstream regulatory proteins influenced by Trim21. OC-specific Trim21 deletion alleviated OVX-induced bone loss by inhibiting bone resorption and preserving bone mass. Myeloid-specific Trim21 deletion impaired OC differentiation and suppressed the expression of key OC markers. Thioredoxin-interacting protein (Txnip), was identified as a downstream effector regulated by Trim21. Trim21 deletion attenuates osteoporosis-induced bone loss, likely by suppressing osteoclast differentiation through modulation of Txnip, thereby presenting a potential novel therapeutic target for osteoporosis treatment.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"15 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756440","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 utility of lung ultrasound in the assessment of interstitial lung disease associated with rheumatoid arthritis","authors":"Shaoyu Zheng, Zexuan Zhou, Guangzhou Du, Qingzi Chen, Shaoqi Chen, Jianqun Lin, Shijian Hu, Weijin Zhang, Kedi Zheng, Jinghua Zhuang, Meigan Huang, Barbara Ruaro, Cosimo Bruni, Anna-Maria Hoffmann-Vold, Marco Matucci-Cerinic, Daniel E. Furst, Yukai Wang","doi":"10.1186/s13075-025-03626-4","DOIUrl":"https://doi.org/10.1186/s13075-025-03626-4","url":null,"abstract":"To investigate the diagnostic accuracy of lung ultrasound (LUS) for interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). This retrospective study included patients over 18 years with RA evaluated at the Department of Rheumatology and Immunology of Shantou Central Hospital. All patients underwent chest high-resolution computed tomography (HRCT) and LUS within one month. The LUS was performed in a total of 50 scanning sites (ScS), and the number of B-lines present in each ScS was counted and summed up as B-lines score. A positive judgement was given on LUS when the B-lines score exceeded 10. The presence and patterns of ILD were defined by HRCT findings. ROC curve analysis was used to calculate the accuracy of LUS to detect ILD. A total of 120 RA patients (86 women, with a median age of 56.0 [50.0–64.0] years) were enrolled. Based on the HRCT, 76 patients were found to have radiographic ILD, with 63 exhibiting nonspecific interstitial pneumonia (NSIP) and 13 showing usual interstitial pneumonia (UIP). Sonographic ILD was detected in 76 patients who underwent LUS examination. The concordance rate between two modalities was 83.33% (Kappa value = 0.64, 95% CI 0.50–0.78). The diagnostic sensitivity and specificity of LUS were 86.84% and 77.27%, respectively. The positive predictive value, negative predictive value, a positive likelihood ratio and a negative likelihood ratio were 86.84%, 77.27%, 3.82, and 0.17, respectively. The number of B-lines in RA with ILD and without ILD on HRCT showed a significant difference (34.0 [15.0–96.5] vs. 6.5 [2.5–10.0], P < 0.001). The presence of 12 B-lines on 50 ScS was the optimal cutoff value for detecting RA-ILD (AUC = 0.89, 95% CI 0.82–0.94, sensitivity of 85.53%, specificity of 81.82%, P < 0.001). Lung ultrasound is a valuable diagnostic tool for RA-ILD and can be used as a screening method to identify patients who require further evaluation with chest HRCT.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"28 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737510","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":"Prevalence, characteristics, and outcomes of patients with low baseline C-reactive protein in giant cell arteritis","authors":"Samuel Pichon, Vincent Koether, Amélie Leurs, Aurelien Chepy, Benoît Gachet, Vincent Sobanski, David Launay, Marc Lambert, Eric Hachulla","doi":"10.1186/s13075-025-03594-9","DOIUrl":"https://doi.org/10.1186/s13075-025-03594-9","url":null,"abstract":"Elevated inflammatory markers play a crucial role in the diagnosis and follow-up of patients with giant cell arteritis (GCA). This study aimed to describe the prevalence, characteristics, and outcomes of patients with low baseline (< 10 mg/L) C-reactive protein (CRP) in GCA. A retrospective observational study was conducted at Lille University Hospital, involving all patients diagnosed with GCA between January 2000 and April 2023. Patients were categorized based on their CRP level at diagnosis. Baseline characteristics, clinical manifestations, laboratory findings, imaging results, and outcomes were compared between patients with baseline CRP < 10 mg/L (“low CRP”) and those with CRP ≥ 10 mg/L (“high CRP”). Of the 380 patients, 7.6% (n = 29) had baseline CRP < 10 mg/L at diagnosis. When compared to the high CRP group, the low CRP group exhibited a lower incidence of fever, and had a higher incidence of ocular involvement, particularly anterior ischemic optic neuropathy (28% vs. 13%, p = 0.04), and limb claudication (24% vs. 8%, p < 0.01). Plasma fibrinogen levels were elevated (> 4 g/L) in 77% of patients with low CRP. Despite differences in clinical presentation, relapse rates were equilibrated between the two groups. GCA patients with low CRP are not rare and present with more ocular and peripheral vascular involvement and less constitutional symptoms in our study. Elevated fibrinogen in these patients suggests active inflammation despite low CRP. Clinicians should consider GCA even with a CRP < 10 mg/L, as these patients may present with severe complications.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"25 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737749","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":"Exploration of bioactive variants of the BMP7-derived p[63–82] peptide for ameliorating the OA-associated chondrocyte phenotype","authors":"Jessica S. J. Steijns, Tim J. M. Welting, Andy Cremers, Guus G. H. van den Akker, Pieter J. Emans, Lodewijk W. van Rhijn, Marjolein M. J. Caron","doi":"10.1186/s13075-025-03599-4","DOIUrl":"https://doi.org/10.1186/s13075-025-03599-4","url":null,"abstract":"Osteoarthritis is a highly prevalent, age-associated joint disease characterized by cartilage degeneration, joint dysfunction, and chronic pain. We previously developed a bone morphogenetic protein 7 derived peptide p[63–82], which may be a novel disease-modifying treatment option for OA. In this study we aimed to optimize the bioactivity and biostability of this peptide in the intra-articular environment to evaluate the therapeutic potential of these peptides to treat osteoarthritis. 33 peptide modifications of p[63–82] were custom-designed and synthesized to optimize the bioactivity. Chondrocytes and synovial fluid were collected from end-stage osteoarthritic patients at total knee arthroplasty surgery. To validate improvements in bioactivity, gene expression analysis, glycosaminoglycan content, matrix metalloproteinase-13 protein levels and alkaline phosphatase activity was measured. Several biochemical approaches were used to explore optimization of the original p[63–82] peptide. One cyclized peptide (C2) was able to significantly increase the expression of collagen type 2 and decrease expression of collagen type 10, matrix metalloproteinase-13 and prostaglandin-endoperoxide synthase 2. The linear p[63–82] peptide and the cyclic peptide variant C2 in the same concentration were effective in suppressing the osteoartritic phenotype in SW1353 cells, despite the presence of interleukin-1β or osteoarthritic-synovial fluid. However, peptide variant C2 had a significantly more favorable bioactivity as compared to p[63–82] in reducing matrix metalloproteinase-13 protein levels in the osteoarthritic-synovial fluid exposed condition. At lower concentrations, the cyclic peptide C2 showed a higher bioactivity as compared to the linear p[63–82] peptide. When the activity of both peptides on primary human articular chondrocytes was evaluated, we found that the linear p[63–82] peptide as well as peptide C2 counteract the hypertrophic and inflammatory state of primary OA chondrocytes. This study demonstrates that among various tested modifications of p[63–82], one cyclic variant (C2) showed similar results in bioactivity as compared to the linear peptide p[63–82], whilst the other modified peptide variants had inactive bioactive properties as compared to the original p[63–82] peptide. This highlights the challenge in enhancing peptide properties without compromising their biological activity and emphasises the need for a cautious approach in peptide modification for therapeutic use. This research underscores that while cyclization and other structural changes may offer benefits, they should be carefully evaluated on a case-by-case basis.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"10 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737729","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}