Estrogen Inhibits Bone Resorption by Directly Inducing Apoptosis of the Bone-resorbing Osteoclasts |
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| Authors: | Takashi Kameda Hiroshi Mano Tatsuhisa Yuasa Yoshihisa Mori Koshi Miyazawa Miho Shiokawa Yukiya Nakamaru Emi Hiroi Kenji Hiura Akira Kameda Na N. Yang Yoshiyuki Hakeda Masayoshi Kumegawa |
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| Affiliation: | From the *Department of Orthodontics, Nippon Dental University School of Dentistry at Niigata, Niigata 951, Japan; ‡Department of Oral Anatomy, Meikai University School of Dentistry, Sakado, Saitama 350-02, Japan; and §Endocrine Research, Eli Lilly & Co., Indianapolis, Indiana 46285 |
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| 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. |
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