Author/Authors :
Takashi Nakamura، نويسنده , , Yuuki Imai، نويسنده , , Takahiro Matsumoto، نويسنده , , Shingo Sato، نويسنده , , Kazusane Takeuchi، نويسنده , , Katsuhide Igarashi، نويسنده , , Yoshifumi Harada، نويسنده , , Yoshiaki Azuma، نويسنده , , Andree Krust، نويسنده , , Yoko Yamamoto، نويسنده , , Hiroshi Nishina، نويسنده , , Shu Takeda، نويسنده , , Hiroshi Takayanagi، نويسنده , , Daniel Metzger، نويسنده , , Jun Kanno، نويسنده , , Kunio Takaoka، نويسنده , , T. John Martin، نويسنده , , Pierre Chambon، نويسنده , , Shigeaki Kato، نويسنده ,
Abstract :
Estrogen prevents osteoporotic bone loss by attenuating bone resorption; however, the molecular basis for this is unknown. Here, we report a critical role for the osteoclastic estrogen receptor α (ERα) in mediating estrogen-dependent bone maintenance in female mice. We selectively ablated ERα in differentiated osteoclasts (ERαΔOc/ΔOc) and found that ERαΔOc/ΔOc females, but not males, exhibited trabecular bone loss, similar to the osteoporotic bone phenotype in postmenopausal women. Further, we show that estrogen induced apoptosis and upregulation of Fas ligand (FasL) expression in osteoclasts of the trabecular bones of WT but not ERαΔOc/ΔOc mice. The expression of ERα was also required for the induction of apoptosis by tamoxifen and estrogen in cultured osteoclasts. Our results support a model in which estrogen regulates the life span of mature osteoclasts via the induction of the Fas/FasL system, thereby providing an explanation for the osteoprotective function of estrogen as well as SERMs.
