Fiche publication
Date publication
septembre 2007
Journal
Cell
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
,
Dr METZGER Daniel
Tous les auteurs :
Nakamura T, Imai Y, Matsumoto T, Sato S, Takeuchi K, Igarashi K, Harada Y, Azuma Y, Krust A, Yamamoto Y, Nishina H, Takeda S, Takayanagi H, Metzger D, Kanno J, Takaoka K, Martin TJ, Chambon P, Kato S
Lien Pubmed
Résumé
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 alpha (ERalpha) in mediating estrogen-dependent bone maintenance in female mice. We selectively ablated ERalpha in differentiated osteoclasts (ERalpha(DeltaOc/DeltaOc)) and found that ERalpha(DeltaOc/DeltaOc) 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 ERalpha(DeltaOc/DeltaOc) mice. The expression of ERalpha 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.
Mots clés
Animals, Antigens, CD95, metabolism, Apoptosis, Bone Density, Bone Diseases, Metabolic, metabolism, Bone Remodeling, drug effects, Cathepsin K, Cathepsins, genetics, Cell Differentiation, Cells, Cultured, Estradiol, metabolism, Estrogen Receptor alpha, deficiency, Fas Ligand Protein, genetics, Female, Integrases, genetics, Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Mice, Transgenic, Osteoclasts, drug effects, Ovariectomy, Phenotype, Selective Estrogen Receptor Modulators, pharmacology, Signal Transduction, Tamoxifen, pharmacology
Référence
Cell. 2007 Sep;130(5):811-23
