Repression of osteoblast maturation by ERRalpha accounts for bone loss induced by estrogen deficiency.
Fiche publication
Date publication
janvier 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SORG Tania
Tous les auteurs :
Gallet M, Saidi S, Hay E, Photsavang J, Marty C, Sailland J, Carnesecchi J, Tribollet V, Barenton B, Forcet C, Birling MC, Sorg T, Chassande O, Cohen-Solal M, Vanacker JM
Lien Pubmed
Résumé
ERRalpha is an orphan member of the nuclear receptor family, the complete inactivation of which confers resistance to bone loss induced by ageing and estrogen withdrawal to female mice in correlation with increased bone formation in vivo. Furthermore ERRalpha negatively regulates the commitment of mesenchymal cells to the osteoblast lineage ex vivo as well as later steps of osteoblast maturation. We searched to determine whether the activities of ERRalpha on osteoblast maturation are responsible for one or both types of in vivo induced bone loss. To this end we have generated conditional knock out mice in which the receptor is normally present during early osteoblast differentiation but inactivated upon osteoblast maturation. Bone ageing in these animals was similar to that observed for control animals. In contrast conditional ERRalphaKO mice were completely resistant to bone loss induced by ovariectomy. We conclude that the late (maturation), but not early (commitment), negative effects of ERRalpha on the osteoblast lineage contribute to the reduced bone mineral density observed upon estrogen deficiency.
Référence
PLoS One. 2013;8(1):e54837