The role of estrogen receptor alpha in growth plate cartilage for longitudinal bone growth.
Fiche publication
Date publication
décembre 2010
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
Tous les auteurs :
Borjesson AE, Lagerquist MK, Liu C, Shao R, Windahl SH, Karlsson C, Sjogren K, Moverare-Skrtic S, Antal MC, Krust A, Mohan S, Chambon P, Savendahl L, Ohlsson C
Lien Pubmed
Résumé
Estrogens enhance skeletal growth during early sexual maturation, whereas high estradiol levels during late puberty result in growth plate fusion in humans. Although the growth plates do not fuse directly after sexual maturation in rodents, a reduction in growth plate height is seen by treatment with a high dose of estradiol. It is unknown whether the effects of estrogens on skeletal growth are mediated directly via estrogen receptors (ERs) in growth plate cartilage and/or indirectly via other mechanisms such as the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis. To determine the role of ERalpha in growth plate cartilage for skeletal growth, we developed a mouse model with cartilage-specific inactivation of ERalpha. Although mice with total ERalpha inactivation displayed affected longitudinal bone growth associated with alterations in the GH/IGF-1 axis, the skeletal growth was normal during sexual maturation in mice with cartilage-specific ERalpha inactivation. High-dose estradiol treatment of adult mice reduced the growth plate height as a consequence of attenuated proliferation of growth plate chondrocytes in control mice but not in cartilage-specific ERalpha(-/-) mice. Adult cartilage-specific ERalpha(-/-) mice continued to grow after 4 months of age, whereas growth was limited in control mice, resulting in increased femur length in 1-year-old cartilage-specific ERalpha(-/-) mice compared with control mice. We conclude that during early sexual maturation, ERalpha in growth plate cartilage is not important for skeletal growth. In contrast, it is essential for high-dose estradiol to reduce the growth plate height in adult mice and for reduction of longitudinal bone growth in elderly mice.
Référence
J Bone Miner Res. 2010 Dec;25(12):2414-24