Arthritis Research & Therapy最新文献

{"title":"Quercetagetin alleviates inflammatory osteoclastogenesis and collagen antibody-induced arthritis via Nrf2 signaling and Pten/AKT/Nfatc1 axis","authors":"Haojue Wang, Tao Yuan, Jingpeng Wang, Dengju Li, Wayne Yuk-wai Lee, Ziqing Li, Shui Sun","doi":"10.1186/s13075-025-03522-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03522-x","url":null,"abstract":"Quercetagetin, a flavonoid derived from the natural herb Flos eriocauli, is used in traditional Chinese medicine for its fire-purging (anti-inflammation) and wind-expelling (pain-alleviating) properties. However, its potential effects concerning rheumatoid arthritis (RA) remain underexplored. This study was designed to elucidate the potential associations between Quercetagetin and RA, establishing the therapeutic potential of Quercetagetin and related mechanisms in RA treatment. Network pharmacology was conducted to decipher related targets and signaling pathways between Quercetagetin and RA. In vitro assays were then conducted to explore the effects of Quercetagetin on osteoclast cell behaviors and corresponding signaling pathways. In vivo study further validated the therapeutic effect of Quercetagetin in collagen antibody-induced arthritis (CAIA) mice. The network pharmacological analysis indicated an intimate correlation of Quercetagetin with RA-related inflammatory osteolysis treatment. Pertaining to biological validations, 2 µM of Quercetagetin successfully inhibited LPS-driven osteoclast differentiation and function. qPCR assay and Western blot analyses denoted parallel changes in osteoclastic marker genes and proteins. Further mechanism study uncovered the effect of Quercetagetin in stimulating the Nrf2/Keap1 signaling pathway and moderating the Pten/AKT/Nfatc1 axis in osteoclasts. In vivo study revealed 40 mg/kg Quercetagetin every day could significantly relief joint destruction in CAIA mice. Our study presents Quercetagetin ‘s therapeutic potential in treating RA, outlining its effects and potential mechanisms in suppressing LPS-induced osteoclast activity, and alleviating inflammatory bone destruction in CAIA model, thereby laying the groundwork for further translational research on Quercetagetin and Flos eriocauli in RA treatment. Quercetagetin extracted from Flos eriocauli displayed brilliant anti-osteoclast and anti-inflammation potential during rheumatoid arthritis. Quercetagetin significantly repressed lipopolysaccharide-stimulated osteoclast behavior from phenotypical and molecular level. Quercetagetin mitigated inflammatory bone destruction in collagen antibody-induced arthritis.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"20 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575093","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":"Comparative effectiveness of subcutaneous sarilumab 200 mg biweekly, subcutaneous Tocilizumab 162 mg biweekly, and intravenous Tocilizumab 8 mg/kg every 4 weeks in patients with rheumatoid arthritis: a prospective cohort study","authors":"Akira Onishi, Masao Tanaka, Takayuki Fujii, Koichi Murata, Kosaku Murakami, Motomu Hashimoto, Ryu Watanabe, Yuji Nozaki, Chisato Ashida, Wataru Yamamoto, Hirotaka Yamada, Sho Sendo, Kosuke Ebina, Hidehiko Makino, Yonsu Son, Yumiko Wada, Kenichiro Hata, Shuichi Matsuda, Akio Morinobu","doi":"10.1186/s13075-025-03514-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03514-x","url":null,"abstract":"While targeting the interleukin-6 receptor (IL-6R) through the use of sarilumab (SAR) or tocilizumab (TCZ) has become a major therapeutic approach for rheumatoid arthritis (RA), direct comparisons between IL-6R inhibitors (IL-6Ris) for treating RA have not been conducted. We aimed to compare the effectiveness of subcutaneous sarilumab (SAR-SC), subcutaneous tocilizumab (TCZ-SC), and intravenous TCZ (TCZ-IV) against RA in a multicenter cohort study. Within the target trial emulation framework, an incident new-user and active-comparator cohort design was used. The source population was the entire cohort of a multicenter prospective study (the ANSWER cohort study) in Japan from 2009 to 2023. We consecutively included patients with IL-6Ri-naïve RA who initiated treatment with SAR-SC 200 mg biweekly, TCZ-SC 162 mg biweekly, or TCZ-IV 8 mg/kg every 4 weeks as the approved starting dose and dosing interval at baseline. The primary outcome of interest was the change in the clinical disease activity index (CDAI) at 24 weeks. In total, 1001 IL-6Ri-naïve patients were included (SAR-SC 200 mg biweekly, 201 patients; TCZ-SC 162 mg biweekly, 546; TCZ-IV 8 mg/kg every 4 week, 254). The improvement in CDAI at 24 weeks (primary outcome) was statistically significantly greater in the SAR-SC group than in the TCZ-SC group (-2.53, 95% confidence interval (CI): -4.38 to -0.69, p = 0.007), but that in TCZ-IV was not significantly different from that in TCZ-SC (1.00, 95% CI: -0.68 to 2.69, p = 0.243). Similar results were noted regarding the changes in CDAI at weeks 4, 12, and 48. The retention rates at 48 weeks in SAR-SC and TCZ-IV did not significantly differ from that in TCZ-SC. SAR-SC 200 mg biweekly initiation was associated with a statistically significantly greater decrease in disease activity than TCZ-SC 162 mg biweekly in IL-6Ri-naïve patients with RA. In contrast, no statistically significant differences were identified between TCZ-IV 8 mg/kg every 4 week and TCZ-SC 162 mg biweekly. However, the effect size of our findings should necessitate careful consideration of the cost difference between TCZ-SC 162 mg biweekly including its biosimilars and SAR-SC 200 mg biweekly.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569535","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":"SDF-1 alleviates osteoarthritis by resolving mitochondrial dysfunction through the activation of the Sirt3/PGC-1α signalling pathway","authors":"Yanping Zhao, Dan Lin, Xiaoying Zhu, Jingyao Yan, Yan Liang, Yanli Wang, Tianqi Dai, Zhiyi Zhang, Shuya Wang","doi":"10.1186/s13075-025-03509-8","DOIUrl":"https://doi.org/10.1186/s13075-025-03509-8","url":null,"abstract":"Osteoarthritis (OA) is the most common form of joint disease. Currently, OA treatment is limited to controlling symptoms. Our previous study showed that stromal cell-derived factor 1 (SDF-1) delayed the progression of OA to a certain extent. The aim of this study was to explore the specific mechanism of SDF-1 in OA. OA chondrocytes and a collagen-induced osteoarthritis (CIOA) mouse model were used as in vitro and in vivo models, respectively. SDF-1 was used to treat OA in vitro and in vivo. To explore the mechanism of SDF-1 in OA treatment, we pretreated chondrocytes with a Sirt 3 inhibitor and assessed mitochondrial function and then analysed related indicators of cartilage anabolic and cartilage metabolism. SOD2 and PGC-1α levels were significantly lower in OA chondrocytes and the cartilage of CIOA model mice than in normal chondrocytes, and mitochondrial dysfunction occurred in OA. After treating OA chondrocytes and CIOA model mice with exogenous SDF-1, mitochondrial dysfunction and abnormal biomarkers of OA normalized. The pretreatment of OA chondrocytes with a Sirt 3 inhibitor or mitochondrial function inhibitor before SDF-1 exposure reversed these changes. SDF-1 can alleviate OA by resolving mitochondrial dysfunction through the activation of the Sirt3/PGC-1α signalling pathway, and therefore, SDF-1 may be a good candidate as a new treatment for OA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"85 4 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569532","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":"Enhanced systemic oxidative stress response in patients with idiopathic inflammatory myopathies","authors":"Anna Mikołajczyk-Korona, Radosław Dziedzic, Krzysztof Wójcik, Magdalena Olchawa, Tadeusz Sarna, Jakub Pięta, Bogdan Jakiela, Lech Zaręba, Jan G. Bazan, Daniel P. Potaczek, Joanna Kosałka-Węgiel, Mateusz Socha, Piotr Kuszmiersz, Agnieszka Padjas, Stanisława Bazan-Socha","doi":"10.1186/s13075-025-03511-0","DOIUrl":"https://doi.org/10.1186/s13075-025-03511-0","url":null,"abstract":"Idiopathic inflammatory myopathies (IIM) are characterized by chronic inflammation, endothelial dysfunction, and muscle tissue mitochondrial defect, leading to the local oxidative stress response. However, data on its systemic intensity and correlation with IIM clinical and laboratory characteristics remains scarce. In clinically stable dermatomyositis (n = 18) and myositis (n = 38) patients and matched controls (n = 50), we measured global oxidative stress response in peripheral blood using a novel coumarin boronic acid (CBA) assay enabling real-time detection of protein hydroperoxides (HP) formed in serum. We documented 36% faster kinetics (p < 0.001) and a 68% increase in the cumulative (p = 0.003) fluorescent product generation in the IIM group compared to the control, which indicates higher HP formation associated with systemic oxidative stress. The dynamics of fluorescent product growth were similar in the dermatomyositis and myositis groups. Interestingly, myositis patients with a marked increase in HP formation were characterized by lower serum myoglobin levels (p = 0.038). There was also an inverse correlation between serum myoglobin and the kinetics of HP formation (e.g., for cumulative in-time generation r = –0.35, p = 0.03). The systemic oxidative stress response measures were not related to clinical characteristics of the disease and treatment, internal medicine comorbidities, smoking status, or autoantibody profile. IIM are characterized by a global pro-oxidant imbalance reflected by enhanced HP generation in serum. Furthermore, muscle weakening without active signs of muscle damage may be related to the increased local and systemic oxidative stress response, suggesting non-inflammatory pathomechanism of the disease that our technically undemanding assay may evaluate.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"37 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569541","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 C4d with disease activity in anti-neutrophil cytoplasmic antibody-associated vasculitis: evidence for classical/lectin complement pathway activation","authors":"Anna Juto, Myriam Martin, Albin Björk, Leonid Padyukov, Caroline Grönwall, Aleksandra Antovic, Annette Bruchfeld, Iva Gunnarsson, Anna M. Blom","doi":"10.1186/s13075-025-03503-0","DOIUrl":"https://doi.org/10.1186/s13075-025-03503-0","url":null,"abstract":"We aimed to investigate the involvement of the classical/lectin complement pathway in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) by exploring the complement activation fragment C4d in association to AAV activity. Forty patients with active AAV and twenty population-based controls were included. The study included 27 (67.5%) patients with a diagnosis of GPA and 13 (32.5%) with MPA. Twenty-four patients (60%) were anti-proteinase 3 (PR3)-ANCA positive and 16 (40%) anti-myeloperoxidase (MPO)-ANCA positive. Thirty-three (82.5%) patients had kidney involvement. A follow-up sample obtained after induction therapy (median 6 months) was available for 24 of the patients, of whom 20 were in remission. Plasma C4d was analysed by ELISA detecting an epitope that arises upon complement-mediated cleavage. Plasma complement factor 4 (C4) and the soluble terminal complement complex (sTCC) were analysed by ELISA. The C4d/C4 ratio was calculated. HLA-DRB1-typing and immunohistochemistry for C4d in kidney biopsies were performed. Patients with active AAV had higher C4d, sTCC levels and C4d/C4 ratio than controls (p < 0.001, p = 0.004, p < 0.001). C4d, sTCC levels and C4d/C4 ratio all decreased from active disease to remission (p = 0.010, p = 0.009, p = 0.011). C4d levels in AAV patients in remission remained higher than population-based controls (p = 0.026). Active anti-PR3-ANCA patients had higher C4d levels and C4d/C4 ratio than anti-MPO-ANCA patients (p = 0.001, p = 0.007). Patients with active AAV and kidney involvement had lower C4d levels than patients without (p = 0.04). C4d levels and C4d/C4 ratio correlated positively with the percentage of normal glomeruli in kidney biopsies. The immunohistochemistry was negative for C4d in kidney biopsies. The specific C4d assay revealed activity in the classical/lectin complement pathway in AAV, which reflected general disease activity, but was not associated specifically with kidney involvement. C4d levels differed depending on anti-PR3/MPO-ANCA subtypes suggesting differences in complement activation and underlying pathogenetic mechanisms. The findings imply that the classical/lectin complement pathway may play a more significant role in AAV pathogenesis than previously reported and that plasma C4d levels and C4d/C4 ratio may be biomarker candidates for disease activity and treatment outcome monitoring.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"13 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546632","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":"Correction: Intensity-dependent effect of treadmill running on lubricin metabolism of rat articular cartilage","authors":"Guo-Xin Ni, Lei Lei, Yue-Zhu Zhou","doi":"10.1186/s13075-025-03521-y","DOIUrl":"https://doi.org/10.1186/s13075-025-03521-y","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction&lt;/b&gt;&lt;b&gt;: &lt;/b&gt;&lt;b&gt;Arthritis Res Ther 14, R256 (2012)&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;https://doi.org/10.1186/ar4101&lt;/b&gt;&lt;/p&gt;&lt;br/&gt;&lt;p&gt;Following publication of the original article [1], the authors reported an error in Figure 4. In Fig. 4, the representative photographs at transitional, and non-contact areas in the LIR group were partially overlapped. We have corrected the error and the correct figure is as follows. The authors are sorry for not checking this figure carefully before publication.&lt;/p&gt;&lt;p&gt;Incorrect figure 4&lt;/p&gt;&lt;figure&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13075-025-03521-y/MediaObjects/13075_2025_3521_Figa_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure a\" aria-describedby=\"Figa\" height=\"1021\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13075-025-03521-y/MediaObjects/13075_2025_3521_Figa_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;/figure&gt;&lt;p&gt;Correct figure 4&lt;/p&gt;&lt;figure&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13075-025-03521-y/MediaObjects/13075_2025_3521_Figb_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure b\" aria-describedby=\"Figb\" height=\"1021\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13075-025-03521-y/MediaObjects/13075_2025_3521_Figb_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;/figure&gt;&lt;ol data-track-component=\"outbound reference\" data-track-context=\"references section\"&gt;&lt;li data-counter=\"1.\"&gt;&lt;p&gt;Ni GX, Lei L, Zhou YZ. Intensity-dependent effect of treadmill running on lubricin metabolism of rat articular cartilage. Arthritis Res Ther. 2012;14:R256. https://doi.org/10.1186/ar4101.&lt;/p&gt;&lt;p&gt;Article PubMed PubMed Central Google Scholar &lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;p&gt;Download references&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/p&gt;&lt;h3&gt;Authors and Affiliations&lt;/h3&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue (N), Guangzhou, 510515, China&lt;/p&gt;&lt;p&gt;Guo-Xin Ni&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Rehabilitation Medicine, Longyan People’s Hospital, 31 Denggao Road (W), Longyan, 364000, China&lt;/p&gt;&lt;p&gt;Lei Lei&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Rehabilitation, 1st Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, China&lt;/p&gt;&lt;p&gt;Yue-Zhu Zhou&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;span&gt;Authors&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;Guo-Xin Ni&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Lei Lei&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Yue-Zhu Zhou&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;h3&gt;Corresponding author&lt;/","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"81 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538453","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":"Vitamin D and its receptor in skeletal muscle are associated with muscle disease manifestation, lipid metabolism and physical fitness of patients with myositis","authors":"Lucia Vernerová, Martina Vokurková, Nikoleta Alchus Laiferová, Michal Nemec, Maja Špiritović, Oksana Mytiai, Sabína Oreská, Martin Klein, Kateřina Kubínová, Veronika Horváthová, Tereza Kropáčková, László Wenchich, Michal Tomčík, Jozef Ukropec, Barbara Ukropcová, Jiří Vencovský","doi":"10.1186/s13075-025-03516-9","DOIUrl":"https://doi.org/10.1186/s13075-025-03516-9","url":null,"abstract":"Low levels of vitamin D have been associated with several autoimmune diseases. A growing body of evidence supports the association of vitamin D with skeletal muscle damage, regeneration, and energy and lipid metabolism. The aim was to analyse vitamin D and its receptor (VDR) in the muscle tissue of patients with idiopathic inflammatory myopathies (IIM) and to relate them to clinical parameters and muscle lipid and energy metabolism. Forty-six patients with IIM and 67 healthy controls (HC) were included in the study. 27 IIM patients participated in a 24-week exercise intervention. Muscle biopsies were obtained from 7 IIM patients before/after training, 13 non-exercising IIM controls, and 21 HC. Circulating concentrations of 25(OH)D and 1,25(OH)D were measured. Gene expression of VDR and CYP27B1, the enzyme converting 25(OH)D to hormonally active 1,25(OH)D, was determined by qPCR in muscle tissue and primary muscle cells. Lipid oxidative metabolism was assessed in muscle tissue (mRNA, qPCR) and primary muscle cells (radioactive assays). Lower levels of active 1,25(OH)D were observed in IIM patients compared with HC (mean ± SD: 125.0 ± 45.4 vs. 164.7 ± 49.2 pmol/L; p < 0.0001). 25(OH)D was associated with CRP (r = -0.316, p = 0.037), MITAX (r = -0.311, p = 0.040) and HAQ (r = -0.390, p = 0.009) in IIM. After 24 weeks of training, active 1,25(OH)D was associated with MMT8 (r = 0.866, p < 0.0001), FI-2 (r = 0.608, p = 0.013) and HAQ (r = -0.537, p = 0.032). Gene expression of both VDR and CYP27B1 in primary muscle cells decreased after training (p = 0.031 and p = 0.078, respectively). Associations of VDR mRNA in muscle tissue with MMT-8 (IIM: r = -0.559, p = 0.013), serum CK (HC: r = 0.484, p = 0.031), myoglobin (IIM: r = 0.510, p = 0.026) and myostatin (IIM: r = -0.519, p = 0.023) were observed. The expression of VDR in differentiated muscle cells correlated negatively with the complete oxidation of palmitic acid (r = -0.532, p = 0.028). Muscle mRNA of carnitine palmitoyl transferase 1 (CPT1) (downregulated in IIM, p = 0.001) correlated positively with serum 1,25(OH) vitamin D (r = 0.410, p = 0.042). Reduced biologically active vitamin D in circulation suggests its impaired metabolism in IIM. Serum vitamin D levels and gene expression of its receptor and activating enzyme in muscle tissue were modified by regular exercise and associated with disease manifestations, physical fitness, and muscle lipid metabolism of IIM patients.\u0000","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"29 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538556","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":"Does extracorporeal shockwave therapy treat leg length discrepancy? an experimental animal study","authors":"Shun-Wun Jhan, Kuan-Ting Wu, Wen-Yi Chou, Jeng-Wei Chen, Ka-Kit Siu, Wen-Chiung Huang, Ching-Jen Wang, Jai-Hong Cheng","doi":"10.1186/s13075-025-03519-6","DOIUrl":"https://doi.org/10.1186/s13075-025-03519-6","url":null,"abstract":"Extracorporeal shockwave therapy (ESWT) is widely used to treat musculoskeletal diseases, but its impact on adolescents with unhealed epiphyseal plates is concerning. It remains unclear whether ESWT applied to growth plates promotes or inhibits bone growth. Low energy ESWT does not cause damage of articular cartilage and promotes the growth of articular cartilage. Therefore, the application of ESWT to treat the leg length discrepancy is a possibleoption. Here, the 96 adolescent rats were used to demonstrate that different levels of ESWT developed different effects on the epiphyseal plate and bone growth. The effects and safety of ESWT on the epiphyseal plate were measured at different energy levels of 0.1, 0.25, and 0.5 mJ/mm² with 800 impulses, 4 Hz at the 7, 13, and 25 weeks. Additionally, the treatments promoted the growth and length of the tibia bone as the ESWT application by compared with Sham group. Notably, ESWT stimulated the expression of IL-1β at the 7 week, which then decreased by the 25 week. However, no apoptosis signals and cell death were detected, and there was no tissue damage to the epiphyseal plate. The expression of SOX9, BMP2, and BMP4 was observed in the epiphyseal plate following ESWT, suggesting a role in promoting bone growth. Our results suggest that ESWT is a safe therapeutic modality for stimulating bone growth at the epiphyseal plate in adolescents, leading to increased bone length. This approach holds potential for future treatment of patients with leg length discrepancies.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"34 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538405","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":"Burden and determinants of multi-b/tsDMARD failure in psoriatic arthritis","authors":"Rebecca H. Haberman, Kyra Chen, Catherine Howe, Seungha Um, Adamary Felipe, Brianna Fu, Stephanie Eichman, Margaret Coyle, Eileen Lydon, Andrea L. Neimann, Soumya M. Reddy, Samrachana Adhikari, Jose U. Scher","doi":"10.1186/s13075-025-03518-7","DOIUrl":"https://doi.org/10.1186/s13075-025-03518-7","url":null,"abstract":"Despite significant therapeutic advances in psoriatic arthritis (PsA), many patients do not achieve remission and cycle through multiple biologic (b)- or targeted synthetic (ts)- DMARDs. Identifying the underlying reasons for repetitive therapeutic failure remains a knowledge gap. Here we describe prescribing patterns and characteristics of PsA patients with multi-b/tsDMARD failure at the NYU Psoriatic Arthritis Center. Nine hundred sixty PsA patients were enrolled in an observational, longitudinal registry. Demographics, medical history, medication use, and psoriatic disease phenotype were collected. Multi-b/tsDMARD failure was defined as requiring ≥ 4 b/tsDMARDs. Seven hundred twenty-five patients (75%) used ≥ 1 b/tsDMARD during their disease course. The initial b/tsDMARDs prescribed were predominately anti-TNF agents. 166 (17%) patients had multi-b/tsDMARD failure. Compared to those requiring 1 b/tsDMARD, female sex (OR 2.3; 95%CI 1.4–3.8), axial disease (OR 2.1; 95% CI 1.2–3.6), depression (OR 2.0; 95%CI 1.1–3.7), and obesity (OR 1.7; 95%CI 1.0–2.8) were risk factors for multi-b/tsDMARD failure disease after adjustment for age, disease duration, sex, depression, smoking, obesity, and skin severity. Patients with multi-b/tsDMARD failure PsA also had increased disease activity at their clinical visit (i.e., swollen joint count, p = 0.005). In this cohort, 17% patients with PsA experienced multi-b/tsDMARD failure. These patients were more likely to be female, obese, and have higher rates of axial involvement and depression, along with higher active disease activity. This highlights the inflammatory and non-inflammatory drivers of multiple therapeutic failures, underscoring the need for precision medicine strategies and potential non-pharmacologic adjuvant therapies for patients with PsA to improve outcomes and quality of life.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"52 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538450","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":"Unraveling the role of lncRNAs and their associated nearby coding genes in the pathogenesis of systemic lupus erythematosus","authors":"Tao Liu, Mingyue Yang, Xiunan Feng, Xiaojuan Zou, Ying Xia, Lu Chen, Zixin Gao, Ling Zhao, Xiaosong Wang","doi":"10.1186/s13075-025-03510-1","DOIUrl":"https://doi.org/10.1186/s13075-025-03510-1","url":null,"abstract":"The role of long non-coding RNAs (lncRNAs) and their nearby messenger RNAs (mRNAs) in systemic lupus erythematosus (SLE) pathogenesis is not well understood. High-throughput sequencing was utilized to analyze PBMCs obtained from SLE patients. Subsequently, we conducted differential analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and verification through quantitative real-time PCR (qRT-PCR). Additionally, qRT-PCR was used to analyze the levels of lncRNAs or mRNAs in transfected Raji cells. We identified 419 differentially expressed (DE) lncRNAs and their 337 nearby DE mRNAs in SLE patients. More than 67% of the DE lncRNAs were lincRNAs and intronic_lncRNAs. The most significantly regulated nearby mRNAs in SLE patients were LTF and CIRBP, potentially involved in recurrent infection and photosensitivity. GO analysis revealed upregulation of the immune effector process term, with genes such as C1qA, C1qC, C1qB, NLRP3, and CXCL6 participating in this term and the upregulated pertussis signaling pathway. Analysis of the nearby coding genes of 88 lincRNAs indicated that XLOC_185773 had the highest number of nearby encoding genes and was negatively correlated with peripheral blood lymphocyte counts, potentially regulating HARS. Furthermore, LNC_005556, an antisense DE lncRNA, was negatively correlated with lupus nephritis occurrence and may regulate the upregulated IGLL5 in patients. The current study provides insights into the dysregulation of lncRNAs and nearby mRNAs in SLE, highlighting potential key players in the pathogenesis of the disease.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"36 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526270","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}