雌二醇对正常成人成骨细胞基质金属蛋白酶及其抑制因子的影响

Effects of 17β-Estradiol(E2) on the expression of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases in normal human osteoblasts cultures

目的探讨雌二醇(17β-estradiol,E2)对正常人成骨细胞(hOB)基质金属蛋白酶(MMP)及其抑制因子(TIMP)的影响和绝经后骨质疏松的发病机制。方法hOB予雌激素干预后,MMP和TIMP用ELISA检测,MMP活性用明胶酶谱法和ELISA检测。结果观察到发现E2抑制hOBMMP-1蛋白质表达(P<0.001)。E2对hOBMMP-2分泌及蛋白质激活无影响(P>0.05)。E2对hOBTIMP-1蛋白质表达亦无影响(P>0.05)。结论雌激素不足可通过减弱其对成骨细胞MMP-1的抑制作用,促进骨吸收,此可能为绝经后骨质疏松的发病机制之一。

Objective To characterize the effects of E2 on the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMPs) in normal human osteoblast (hOB) in order to understand the mechanism of postmenopausal osteoporosis . Methods ELISA were used to show the actions of E2 on secretion of MMPs and TIMPs by hOB. Gelatin zymogram and ELISA was done to examine the effects of E2 on activity of MMPs.Results E2 inhibited the secretion of MMP-1 in hOB culture. E2 seemed to have no influence on the expression of MMP-2 and TIMP-1 protein in hOB culture, it also have no effect on the activation of latent MMP-2. Conclusion Deficiency of estrogen as seen in postmenopausal women may decrease inhibiting effect on MMP-1 in human osteoblasts, which could lead to the increasing degradation of bone matrix and bone resorption followed by acceleration of bone loss. It probably is one of the key pathogenesis of postmenopausal osteoporosis.