Effects of 17beta-estradiol on the expression of matrix metalloproteinase-1, -2 and tissue inhibitor of metalloproteinase-1 in human osteoblast-like cell cultures.

Estrogen can effectively prevent estrogen deficiency-induced bone loss in animals and humans. However, its mechanism remains unknown. Osteoblast-derived Matrix metalloproteinse-1 (MMP-1), MMP-2, and tissue inhibitor of metalloproteinase-1 (TIMP-1) recently were implicated as playing important roles in initiating bone resorption. Therefore, we tested the effects of 17beta-estradiol (E2) on MMP-1, MMP-2, and TIMP-1 production in cultures of human osteoblastic MG-63 cells and normal human osteoblasts (hOB). MMP-1, MMP-2 and TIMP-1 concentrations in the culture medium were determined by ELISA, and activity of MMP-2 was assessed by ELISA. After 12-48 h of treatment, E2 at 10(-8)M decreased MMP-1 level in cultures of MG-63 cells or hOB. Treatment with increasing, dose of E2 in MG-63 cells or hOB caused a dose-dependent decrease in MMP-1 synthesis. E2 had no influence on MMP-2 and TIMP-1 production in MG-63 cells or hOB cultures, as well as activation of latent MMP-2. In conclusion, E2 represses MMP-1 synthesis, and this effect may contribute to its action on the inhibition of bone resorption, followed by prevention of bone loss. Increasing MMP-1 production followed by estrogen deficiency may contribute to the mechanisms involved in postmenopausal osteoporosis.