Study on direct action of estrogen on mature osteoclasts

点击翻译按钮获取中文摘要

Estrogen deficiency, cause by either menopause ovariectomy, results in pathological bone loss, which can be prevented by estrogen replacement therapy. Although it is believed that estrogen's main action in preventing bone loss is through inhibition of osteoclastic bone resorption, the precise mechanism of such effect is not clear, largely due to technical difficulties in obtaining purified functional osteoclasts. Throughout this study, we used two unique isolation methods of highly purified mammalian osteoclasts, which were recently developed by us : one is the purification on plastic dished to get a large number of osteoclasts for molecular biological analyzes, and the other is the isolation of osteoclasts in cell suspension for estimation of osteoclastic bone-resorbing activity. In a range of physiological concentrations of estrogen (10^<-12>-10^<-10>M), estrogen inhibited osteoclastic bone resorbing activity. In the same concentration range, estrogen also reduced mRNA levels of cathepsin K,which is abundantly and specifically expressed in osteoclasts, and of carbonic anhydrase II,that is involved in proton production in osteoclasts. Furthermore, estrogen induced osteoclast apoptosis in a dose-and time-dependent manner. ICI1164,384 and tamoxifen, as pure and partial antagonists, respectively, completely and partially blocked the effect of estrogen on both inhibition of osteoclastic bone resorption and induction of osteoclast apoptosis. Finally, we detected the mRNA expression of estrogen reccptor (ERA), but not BRb. Thses data suggest that the protective effects of estrogen against postmenopausal osteoporosis are mediated in part by the direct reduction of key enzymes for osteoclastic bone resorption and the direct induction of osteoclast apoptosis via estrogen receptor-mediated mechanisms.