基质金属蛋白酶-13在骨性关节炎发病中的活性调控研究

目的 研究一氧化氮(NO)是否通过膜型基质金属蛋白酶-1(MT1-MMP)间接激活基质金属蛋白酶-13酶原(pro-MMP-13).方法 购买并传代人软骨肉瘤细胞(SW1353),用NO供体S-亚硝基-N-乙酰基青霉胺(SNAP),SNAP+NO清除荆氧合血红蛋白(OxyHb)和SNAP+组织金属蛋白酶抑制物-2(TI...

Activation of matrix metalloproteinase-13 in the osteoarthritis

Objective To investigate the activation mechanism of matrix metalloproteinase-13 zymogen (pro-MMP-13) induced by nitric oxide (NO). Methods Human chondrosarcoma cells (SW1353) were grouped and treated with the NO donor S-nitroso-N-acetyl-penicillamine (SNAP), SNAP + NO scavenger oxyhemoglobin (OxyHb), and SNAP + tissue inhibitor of metalloproteinase material -2 (TIMP-2) respectively. After stimulation, matrix metalloproteinase -13 ( a-MMP-13 ) expression level was detected. Besides, the expression levels of MT1- MMP were detected after SW1353 cells stimulated with SNAP and SNAP + OxyHb, respectively. At last, the activities of the recombinant MMP-13 (r-MMP-13) were detected after r-MMP-13 stimulated with SNAP, recombinant MT1-MMP (r-MT1-MMP) and r-MT1-MMP + TIMP-2,respectively. Results SNAP increased human chondrocytes a-MMP-13 expression, OxyHb and TIMP-2 inhibited a- MMP- 13 expression. SNAP also increased the expression of MT1- MMP levels, OxyHb inhibited the expression of MT1-MMP. r-MT1-MMP activated the r-MMP-13, but SNAP did not, TIMP-2 inhibited the activity of r-MMP-13 induced by r-MT1-MMP. Conclusions NO can not directly activate pro-MMP13 by the role of S-nitroso-(S nitrosylation). MT1-MMP mediates the activiation of pro-MMP-13 induced by NO.