Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
Eur Rev Med Pharmacol Sci. 2017 May;21(10):2329-2337.
Rheumatoid arthritis (RA) is one systemic auto-immune disorder featured as chronic synovitis and can destruct joint cartilage. Fibroblast-like synoviocyte (FLS) secretes various factors affecting chondrocyte matrix and degradation. This study thus investigated the effect of interleukin-17A (IL-17A) on FLS and osteoclast.
Type II collagen-induced arthritis (CIA) rats were assigned to CIA model, CIA + IgG1 isotype, and CIA + Anti-Rat IL-17A groups. Tissue volume and arthritis index (AI) evaluated arthritis condition. ELISA and flow cytometry measured IL-17A content and Th17 cell percentage in joint cavity fluid. Matrix metallopeptidase 13 (MMP-13) and collagen type II alpha 1 (COL2A1) expression in synovial tissues were compared. FLS-osteoclast co-culture system was treated with IL-17A + IgG1 Isotype or CIA + Anti-Rat IL-17A. MMP-13 and COL2A1 expression were compared.
CIA model rats had significantly higher IL-17A and Th17 cell ratio in joint cavity fluid. Injection of Anti-Rat IL-17A decreased AI and tissue volume in model rats, decreased MMP-13 while increased COL2A1 expression in synovial or cartilage tissues. IL-17A treatment remarkably up-regulated MMP-13 mRNA or protein expression in chondrocytes. Anti-IL-17A weakened effects of IL-17A on FLS or chondrocytes.
IL-17A inhibits COL2A1 mRNA and protein expression of chondrocyte in the co-culture system via inducing MMP-13 expression in FLS, thus enhancing collagen degradation and playing a role in RA-related cartilage injury.
类风湿关节炎（RA）是一种以慢性滑膜炎为特征的系统性自身免疫性疾病，可破坏关节软骨。成纤维样滑膜细胞（FLS）分泌各种影响软骨细胞基质和降解的因子。本研究因此探讨了白细胞介素 17A（IL-17A）对 FLS 和破骨细胞的影响。
采用 II 型胶原诱导性关节炎（CIA）大鼠，分为 CIA 模型、CIA+IgG1 同型对照、CIA+抗大鼠 IL-17A 组。组织体积和关节炎指数（AI）评估关节炎情况。酶联免疫吸附试验和流式细胞术检测关节腔液中 IL-17A 含量和 Th17 细胞百分比。比较滑膜组织中基质金属蛋白酶 13（MMP-13）和胶原 II 型 α1 链（COL2A1）的表达。用 IL-17A+IgG1 同型对照或 CIA+抗大鼠 IL-17A 处理 FLS-破骨细胞共培养系统。比较 MMP-13 和 COL2A1 的表达。
CIA 模型大鼠关节腔液中 IL-17A 和 Th17 细胞比例明显升高。注射抗大鼠 IL-17A 可降低模型大鼠的 AI 和组织体积，降低滑膜或软骨组织中 MMP-13 而增加 COL2A1 的表达。IL-17A 处理可显著上调软骨细胞中 MMP-13 mRNA 或蛋白表达。抗 IL-17A 减弱了 IL-17A 对 FLS 或软骨细胞的作用。
IL-17A 通过诱导 FLS 中 MMP-13 的表达，抑制共培养体系中软骨细胞 COL2A1 mRNA 和蛋白的表达，从而增强胶原降解，在 RA 相关的软骨损伤中发挥作用。
