The expression of m-calpain in human synovial fibroblasts and chondrocytes.

m-钙蛋白酶在人滑膜成纤维细胞和软骨细胞中的表达。

• 批准号: 14571368
• 负责人: ITOH Yoshiki
• 金额: $ 1.86万
• 依托单位: Gifu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571368/
• 关键词: calpain; chondrocyte; NSAIDs; TNF-α; arthritis

Calpain is generally believed to function only in the cytoplasm. However, m-calpain has recently been detected in the extracellular spaces of arthritic joint tissues. We attempted to examine the expression and secretion of m-calpain in a human chondrocytic cell line, HCS2/8 stimulated by TNF-α Cells were stimulated by TNF-α, and the expression of m-calpian in the cells and culture medium was analyzed by Western blotting. The effects of NSAIDs on the expression of m-calpain were also examined.TNF-α increased the level of m-calpain in the culture medium in a dose-and time-dependent manner.Intracellular m-calpain increased at 24 h and thereafter gradually to decreased to 48 h. NSAIDs, aspirin, diclofenac sodium, loxoprofen-SRS and NS398 significantly inhibited TNF-α-induced increase of m-calpain in the medium and cells. Prostaglandin E_2 stimulated the effect of low concentrations of TNF-α on m-calpain expression. In contrast, prostanoid-receptor antagonists inhibited the effects of TNF-α.Increase of m-calpain in the culture medium suggests that this Ca^<2+>-dependent protease may play a role in the promotion of degradation of cartilage extra-cellular matrix during arthritis. NSAIDs have protective effects, at least in part, through the inhibition of the expression and secretion of m-calpain.

一般认为钙蛋白酶仅在细胞质中起作用。然而，最近在关节炎关节组织的细胞外间隙中检测到m-calpain。我们试图检测m-calpain在TNF-α刺激的人软骨细胞HCS2/8中的表达和分泌，TNF-α刺激细胞，用Western blotting分析m-calpain在细胞和培养基中的表达。我们还检测了非甾体抗炎药对m-calpain表达的影响。TNF-α以剂量和时间依赖性的方式增加培养基中m-calpain的水平。nsaid、阿司匹林、双氯芬酸钠、loxoprofen-SRS和NS398均能显著抑制TNF-α-诱导的细胞内m-calpain升高。前列腺素E_2刺激低浓度TNF-α对m-calpain表达的影响。相反，前列腺素受体拮抗剂抑制TNF-α的作用。培养基中m-calpain的增加表明这种Ca^<2+>依赖性蛋白酶可能在关节炎期间促进软骨细胞外基质的降解中起作用。非甾体抗炎药具有保护作用，至少部分是通过抑制m-钙蛋白酶的表达和分泌。