Arthritis Research & Therapy最新文献

{"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}

{"title":"Akt2 inhibition alleviates temporomandibular joint osteoarthritis by preventing subchondral bone loss","authors":"Shi-Yang Feng, Meng-Nan Cao, Chen-Chen Gao, Yi-Xin Li, Jie Lei, Kai-Yuan Fu","doi":"10.1186/s13075-025-03506-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03506-x","url":null,"abstract":"This study aimed to investigate the role and mechanism of the Akt2 pathway in different stages of anterior disc displacement (ADD)-induced temporomandibular joint osteoarthritis (TMJOA). A rat model for TMJOA that simulates anterior disc displacement was established. For inhibit Akt2 expression in subchondral bone, rats were intravenously injected with adeno-associated virus carrying Akt2 shRNA at a titer of 1 × 1012 transducing units/mL 10 days before the ADD or sham operations. The rats were euthanized and evaluated 1 or 8 weeks after surgery, as these time points represented the early or advanced stage of ADD. Immunostaining was performed to examine the expression and location of phosphorylated Akt2 in different stages of ADD. Microcomputed tomography, hematoxylin and eosin staining, toluidine blue staining, Western blotting, immunohistochemical and immunofluorescence staining were used to elucidate the pathological changes and potential mechanisms underlying ADD-induced TMJOA. In the rat model of ADD-induced TMJOA, rapid condylar bone loss occurred with increased phosphorylation of Akt2 in subchondral bone macrophages within 1 week post-surgery. At 8 weeks after surgery, abnormal remodeling of subchondral bone and degenerative changes in cartilage were observed. Inhibiting Akt2 reduced condylar bone resorption following ADD surgery while improving condylar bone morphology at 8 weeks post-surgery. Additionally, inhibition of Akt2 alleviated cartilage degeneration characterized by a decreased number of apoptotic chondrocytes, reduced expression of matrix metalloproteinases, and increased collagen type II expression in cartilage tissue. The Akt2 pathway is activated mainly in subchondral bone macrophages during the early stage of ADD and plays an important role in regulating subchondral bone remodeling. Inhibition of Akt2 could serve as a prophylactic treatment to slow the progression of ADD-induced TMJOA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"4 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507224","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":"Longitudinal assessment of structural and locomotor deficits as a prediction of severity in the collagenase-induced mouse model of osteoarthritis","authors":"Anne-Laure Mausset-Bonnefont, Karine Toupet, Christian Jorgensen, Danièle Noël","doi":"10.1186/s13075-025-03507-w","DOIUrl":"https://doi.org/10.1186/s13075-025-03507-w","url":null,"abstract":"The aim of this study was to provide an in-depth longitudinal locomotor and structural characterisation of the collagenase-induced osteoarthritis (CIOA) mouse model, using the most relevant and up-to-date non-invasive locomotor phenotyping and imaging methods. The ultimate goal of this study was to predict histological scores, the gold standard parameter in osteoarthritis (OA), based on locomotor or structural deficits. The CIOA model was induced in C57BL/6 male mice, which were then maintained in their home cage with or without a running wheel for 6 weeks. Both global and fine locomotor effects were measured using the open field and Catwalk™ tests. Imaging of bone and cartilage was performed using either µCT, contrast-enhanced µCT or confocal laser scanning microscopy (CLSM) at different time points. Correlations between functional or structural changes and histological scores were sought in order to provide tools for predicting histological degradation. Locomotor deficits were observed at early time points (days 3 to 9) but did not persist to the end of the experiment. Signs of inflammation appeared as early as day 9. They worsened on day 28 as the disease progressed and meniscal calcifications were observed by µCT. The early functional and structural changes correlated with the histological scores measured post mortem and some specific locomotor or structural parameters were identified as predictors of histological changes. Free exercise (voluntary running wheel activity) did not seem to influence the severity of the observed changes. Open-field quantification of kinetic parameters is a simple and timely relevant test to detect early locomotor changes and predict histological changes. Meniscal calcifications and osteophyte formation, which can be observed by µCT at early time points, are also highly predictive of OA severity. These two non-invasive techniques are very useful for longitudinal monitoring of mice and OA score prediction.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"32 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495203","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":"Blood gene expression of Toll-like receptors in SLE patients with lupus nephritis or neuropsychiatric systemic lupus erythematosus","authors":"Marketa Dudkova, Anna Petrackova, Martin Radvansky, Martina Skacelova, Jakub Videman, Jirina Manakova, Veronika Smotkova Kraiczova, Milos Kudelka, Andrea Smrzova, Katerina Langova, Frantisek Mrazek, Eva Kriegova, Pavel Horak","doi":"10.1186/s13075-025-03512-z","DOIUrl":"https://doi.org/10.1186/s13075-025-03512-z","url":null,"abstract":"To determine differences in the blood innate gene expression signatures of systemic lupus erythematosus (SLE) patients across various organ manifestations and disease activity, with a focus on lupus nephritis (LN) and central nervous system (CNS) involvement. Toll-like receptor family (TLR 1–10) mRNA expression was investigated in peripheral blood mononuclear cells from patients with SLE (n = 74) and healthy controls (n = 34). We compared patients with histologically confirmed active LN or neuropsychiatric systemic lupus erythematosus (NPSLE) with patients without these symptoms. The expression of TLR mRNA was determined by RT‒qPCR using a high-throughput SmartChip Real-Time-qPCR system (WaferGen). Multivariate analysis and nonparametric statistics were used for data analysis to assess the associations between TLRs and disease activity and severity. TLR4 (0.044 vs. 0.081, p = 0.012) was upregulated and TLR10 (0.009 vs. 0.006, p = 0.0007) was downregulated in the whole cohort of SLE patients compared to healthy controls. A comparison of the active LN group with participants without kidney involvement revealed increased expression of TLR2 (0.078 vs. 0.03, p = 0.009), and TLR5 (0.035 vs. 0.017, p = 0.03). Moreover, a significant difference was observed in TLR9 expression between inactive LN and the control group (0.014 vs. 0.009, p = 0.01), together with borderline correlation in TLR2 expression (0.04 vs. 0.03, p = 0.06). Receiver operating characteristic (ROC) curve analysis revealed that TLR1 and TLR2 expression were the best potential diagnostic markers for active LN. The NPSLE group showed upregulation of TLR1 (0.088 vs. 0.048, p = 0.01), TLR4 (0.173 vs. 0.066, p = 0.0003) and TLR6 (0.087 vs. 0.036, 0.007). Our correlation analysis supported the close relationships among the expression of individual TLRs in the whole lupus cohort and its subgroups. Our study revealed differences in TLR expression between a lupus cohort and healthy controls. Additionally, our analysis provides insight into specific TLR expression in cases with severe organ manifestations, such as LN and NPSLE. The multiple mutual relationships of TLRs demonstrate the activation of innate immunity in SLE and suggest promising targets for future therapies or diagnostics.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"32 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495204","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}