Estrogen Inhibits Bone Resorption by Directly Inducing Apoptosis of the Bone-resorbing Osteoclasts

Abstract

Estrogen deficiency causes bone loss, which can be prevented by estrogen replacement therapy. Using a recently developed technique for isolation of highly purified mammalian osteoclasts, we showed that 17 β-estradiol (E2) was able to directly inhibit osteoclastic bone resorption. At concentrations effective for inhibiting bone resorption, E2 also directly induced osteoclast apoptosis in a dose- and time-dependent manner. ICI164,384 and tamoxifen, as pure and partial antagonists, respectively, completely or partially blocked the effect of E2 on both inhibition of osteoclastic bone resorption and induction of osteoclast apoptosis. These data suggest that the protective effects of estrogen against postmenopausal osteoporosis are mediated in part by the direct induction of apoptosis of the bone-resorbing osteoclasts by an estrogen receptor– mediated mechanism.

Oligogalacturonic acid inhibit bone resorption and collagen degradation through its interaction with type I collagen

“…Evaluation of apoptosis was carried out as previously described (9). After a 48 hour treatment, cells were fixed in 3.7 % formaldehyde solution for 5 min and stained with 0.2 mM Hoechst 33258 (SIGMA, France) for 10 min.…”

“…Most of them have shown the capacity to reduce bone resorption e.g. estrogens (9), bisphosphonates (10), calcitonin (11), selective oestrogen receptor modulators (12). However, to date, none of these agents has been able to completely abolish the development of new bone fractures.…”

Unraveling estrogen action in osteoporosis

“…28 This groundbreaking observation led the way for the exploration of the mechanism of how estrogen caused apoptosis. Kousteni, et al, suggested that apoptosis in osteoclasts was induced via a non-genomic pathway 3 .…”

Estradiol Abrogates Apoptosis in Breast Cancer Cells through Inactivation of BAD: Ras-dependent Nongenomic Pathways Requiring Signaling through ERK and Akt

“…Estrogens, in particular 17-␤ estradiol (E 2 ), are well-characterized mitogens for mammary tissues and epithelial cells of the female reproductive tract. Whereas estrogens exert antiapoptotic influence in neurons (Zhang et al, 2001), epithelial cells of the female reproductive tract (Leung and Wang, 1999;Choi et al, 2001), immune system, blood cells, and endothelial cells (Bynoe et al, 2000;Haynes et al, 2000), they also have significant apoptotic effects on certain classes of bone-derived cells (Hughes et al, 1996;Kameda et al, 1997) and some immune system cells (Zajchowski and Hoffman-Goetz, 2000;Okasha et al, 2001).…”