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意义，获得以下结果. RA患者滑液中凝血酶和肥大细胞类胰蛋白酶（MCT）活性显著高于骨关节炎（OA）和健康受试者。在滑膜组织中，MCT活性在RA和OA中相似。除PAR-2 mRNA转录表达外，RA和OA之间的滑膜PAR表达无显著差异3。凝血酶和MCT可促进滑膜成纤维样细胞的增殖和IL-8的释放.此外，PAR-2激活肽刺激滑膜成纤维细胞样细胞释放IL-8，表明滑液中的肥大细胞类胰蛋白酶刺激滑膜成纤维细胞样细胞的增殖，并通过激活PAR-2.5从这些细胞释放IL-8。这项研究表明，相对于OA，RA的滑液中肥大细胞类胰蛋白酶的非糖基化形式以更高的浓度积累，并且与OA相比，RA中滑膜PAR-2 mRNA转录物的表达更高。相对于OA，RA中肥大细胞类胰蛋白酶和凝血酶向滑液中的分泌更高，刺激了RA中滑膜的更高增殖和促炎细胞因子的产生。RA与OA的SFC比较。

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.