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植物分子朝藿定C减轻大鼠软骨细胞外基质降解和骨关节炎进展

Phytomolecule Epimedin C Mitigates Cartilage Extracellular Matrix Degradation and Osteoarthritis Progression in Rats.

作者信息

Yang Wenyao, Meng Xiangbo, Li Jiming, Cao Huijuan, Li Ling, Huang Cuishan, Wang Yingchao, Chang Wakam, Grad Sibylle, Li Zhen, Qin Ling, Wang Xinluan

机构信息

Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

Faculty of Health Sciences, University of Macau, Macau, 999078, China.

出版信息

Adv Biol (Weinh). 2025 Aug;9(8):e2400685. doi: 10.1002/adbi.202400685. Epub 2025 Apr 8.

DOI:10.1002/adbi.202400685
PMID:40197728
Abstract

Osteoarthritis (OA) is a common degenerative joint disease associated with chronic inflammation. Epimedin C (EpiC), flavonoid from Epimedin, enhances the extracellular matrix (ECM) expression in human chondrocytes in vitro. This study aims to investigate the effects of EpiC on osteoarthritis progress in vivo. OA is induced in Lewis rats by medial meniscus transection and treatment with intra-articular injections of EpiC. EpiC treatment reduces joint swelling and improves hindlimb weight distribution in MMT-induced OA rats. Pathological changes in cartilage are observed and evaluated by the osteoarthritis research society international (OARSI) score and both EpiC groups have lower OARSI scores than the OA group. The EpiC groups also exhibit higher positive expressions of collagen II and aggrecan, and lower MMP13 and ADAMTS5 in the cartilage. RNA-seq suggest that EpiC may attenuate MMT-induced ECM degradation by inhibiting the JAK-STAT pathway. EpiC promotes the gene expressions of Col2a1 and Acan, while inhibiting Mmp13 and Col10a1 in cartilage. EpiC reduces the phosphorylated STAT3 in human chondrocyte pellets stimulated with inflammatory cytokines. In conclusion, EpiC demonstrates potential as an OA therapeutic by reducing pain and ECM degradation through p-STAT3 inhibition.

摘要

骨关节炎(OA)是一种与慢性炎症相关的常见退行性关节疾病。淫羊藿苷C(EpiC)是从淫羊藿中提取的黄酮类化合物,可在体外增强人软骨细胞中细胞外基质(ECM)的表达。本研究旨在探讨EpiC在体内对骨关节炎进展的影响。通过内侧半月板横断术并关节内注射EpiC诱导Lewis大鼠患骨关节炎。EpiC治疗可减轻MMT诱导的OA大鼠的关节肿胀并改善后肢重量分布。通过国际骨关节炎研究协会(OARSI)评分观察和评估软骨的病理变化,两个EpiC组的OARSI评分均低于OA组。EpiC组软骨中Ⅱ型胶原蛋白和聚集蛋白聚糖的阳性表达也更高,而MMP13和ADAMTS5更低。RNA测序表明,EpiC可能通过抑制JAK-STAT途径减轻MMT诱导的ECM降解。EpiC促进软骨中Col2a1和Acan的基因表达,同时抑制Mmp13和Col10a1。EpiC可降低炎性细胞因子刺激的人软骨细胞团块中磷酸化的STAT3水平。总之,EpiC通过抑制p-STAT3减轻疼痛和ECM降解,显示出作为OA治疗药物的潜力。

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