Opposite Function of ER alpha and ER beta in Controlling 17 beta-Estradiol-mediated Osteogenesis in Osteoblasts

摘要

Estrogen receptor plays critical roles in osteogenesis but the underlying mechanism remains unclear. In order to determine the effect of ER alpha and ER beta on several critical factors in regulating osteogenesis in human osteoblasts. Cell based assy, RT-PCR and immunoblot analyses were used in the research. Both RT-PCR and immunoblot showed that gene expression of OPG, MBP2, TGF-beta, RUNX2, IGF-1 was significantly reduced while expression of RANKL was drastically increased after shRNA-based depletion of ER alpha in MG-63 osteoblasts. Surprisingly, 17 beta-estradiol (E2) treatment led to remarkably reduced RANKL compared with that in E2 untreated cells. In contrast, ER beta plays an opposite role in regulating gene expression of OPG, MBP2, TGF-beta, RUNX2, IGF-1 and RANKL. However, double depletion of ER alpha and ER beta could not rescue the gene expression of these factors in vitro. Our results provide a novel mechanism of estrogen receptor in controlling osteogenesis in human cells as well as a potential clinic therapeutic target in human osteoporosis. (C) 2016 IMSS. Published by Elsevier Inc.