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

一般认为，钙蛋白酶只在细胞质中起作用。然而，最近在关节炎关节组织的细胞外间隙中检测到m-calain。为探讨m-钙蛋白在人软骨细胞系中的表达和分泌，用肿瘤坏死因子-α刺激人软骨细胞株HCS2/8，用肿瘤坏死因子-α刺激细胞，用Western blotting分析m-钙蛋白在细胞和培养上清液中的表达。NSAIDs、阿司匹林、双氯芬酸钠、洛索洛芬-SRS和NS398均能明显抑制肿瘤坏死因子-α诱导的细胞内和细胞内m-calain的表达，并呈剂量和时间依赖关系，细胞内m-calain的表达在24 h后逐渐升高，至48 h后逐渐下降，而非甾体抗炎药、阿司匹林、双氯芬酸钠、洛索洛芬-SRS和NS398均能明显抑制由TNF-α诱导的细胞内m-calain的增加。前列腺素E_2刺激低浓度肿瘤坏死因子-α对m-calain表达的影响。相反，前列腺素受体拮抗剂可抑制肿瘤坏死因子-α的作用。培养液中m-钙蛋白酶的增加表明，这种钙依赖的蛋白酶可能在促进关节炎时软骨细胞外基质的降解中发挥作用。非类固醇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来实现的。

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.