Estrogen receptor-alpha expression in neuronal cells affects bone mass.
Fiche publication
Date publication
janvier 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
Tous les auteurs :
Ohlsson C, Engdahl C, Borjesson AE, Windahl SH, Studer E, Westberg L, Eriksson E, Koskela A, Tuukkanen J, Krust A, Chambon P, Carlsten H, Lagerquist MK
Lien Pubmed
Résumé
It has generally been assumed that bone mass is controlled by endocrine mechanisms and the local bone environment. Recent findings demonstrate that central pathways are involved in the regulation of bone mass. Estrogen is involved in the regulation of bone homeostasis and the CNS is also a target for estrogen actions. The aim of this study was to investigate in vivo the role of central estrogen receptor-alpha (ERalpha) expression for bone mass. Nestin-Cre mice were crossed with ERalpha(flox) mice to generate mice lacking ERalpha expression specifically in nervous tissue (nestin-ERalpha(-/-)). Bone mineral density was increased in both the trabecular and cortical bone compartments in nestin-ERalpha(-/-) mice compared with controls. Femoral bone strength was increased in nestin-ERalpha(-/-) mice, as demonstrated by increased stiffness and maximal load of failure. The high bone mass phenotype in nestin-ERalpha(-/-) mice was mainly caused by increased bone formation. Serum leptin levels were elevated as a result of increased leptin expression in white adipose tissue (WAT) and slightly increased amount of WAT in nestin-ERalpha(-/-) mice. Leptin receptor mRNA levels were reduced in the hypothalamus but not in bone. In conclusion, inactivation of central ERalpha signaling results in increased bone mass, demonstrating that the balance between peripheral stimulatory and central inhibitory ERalpha actions is important for the regulation of bone mass. We propose that the increased bone mass in nestin-ERalpha(-/-) mice is mediated via decreased central leptin sensitivity and thereby increased secretion of leptin from WAT, which, in turn, results in increased peripheral leptin-induced bone formation.
Référence
Proc Natl Acad Sci U S A. 2012 Jan 17;109(3):983-8