Thrombin and mast cell tryptase are trigger proteases in arthritis.

本研究旨在探讨凝血酶和肥大细胞类胰蛋白酶在类风湿关节炎(RA)和骨关节炎(OA)患者关节病变中的病理生理学意义。RA组关节液中凝血酶和肥大细胞类胰蛋白酶(MCT)活性明显高于骨关节炎(OA)组和正常对照组。在滑膜组织中，MCT活性在RA和OA中相似。RA和OA患者滑膜中PAR的表达除PAR-2mRNA表达外，其余均无显著差异。凝血酶和MCT可促进滑膜成纤维细胞样细胞的增殖和IL-8的释放。此外，PAR-2激活肽可刺激滑膜成纤维细胞样细胞释放IL-8，提示滑液中的肥大细胞类胰蛋白酶通过激活PAR-2.5刺激滑膜成纤维细胞样细胞的增殖和IL-8的释放。本研究表明，类风湿关节炎患者滑液中非糖基化的肥大细胞类胰蛋白酶的浓度高于骨性关节炎患者，且类风湿关节炎患者滑膜组织中PAR-2mRNA的表达高于骨性关节炎患者。综上所述，类风湿关节炎患者关节滑液中肥大细胞类胰蛋白酶和凝血酶的分泌水平高于骨性关节炎患者，从而刺激滑膜细胞的增殖和促炎细胞因子的产生。

The purpose of this study is to clarify the pathophysiological significance of thrombin and mast cell tryptase in articular lesions of patients with rheumatoid arthritis (RA) and osteoarthritis (OA).We obtained the following results.1. Thrombin and mast cell tryptase (MCT) activity in synovial fluid were significantly higher in RA than in osteoarthritis (OA) and healthy subjects. In synovial tissue, MCT activity was similar in RA and OA.2. There was no significant difference in synovial PAR expression between RA and OA, except for expression of PAR-2 mRNA transcripts3. Thrombin and MCT enhanced the proliferation of synovial fibroblast-like cells and the release of IL-8 from these cells.4. Furthermore, PAR-2 activating peptide stimulated the release of IL-8 from synovial fibroblast-like cells, suggesting that mast cell tryptase in synovial fluid stimulates the proliferation of synovial fibroblast-like cells and the release of IL-8 from these cells via activation of PAR-2.5. This study showed that an unglycosylated form of mast cell tryptase accumulated in higher concentration in synovial fluid from RA relative to OA, and that there was higher expression of synovial PAR-2 mRNA transcripts in RA compared with that in OA.In summary, higher secretion of mast cell tryptase and thrombin into synovial fluids in RA relative to OA stimulates higher proliferation of the synovium and production of proinflammatory cytokine in SFCs in RA compared with OA.