Repression of osteoblast maturation by ERRα accounts for bone loss induced by estrogen deficiency.
ERRα 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 ERRα 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 ERRα 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 ERRαKO mice were completely resistant to bone loss induced by ovariectomy. We conclude that the late (maturation), but not early (commitment), negative effects of ERRα on the osteoblast lineage contribute to the reduced bone mineral density observed upon estrogen deficiency.
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Centre national de la recherche scientifique UMR5242, Ecole Normale Supérieure de Lyon, Lyon, France.
Marlène
M
Gallet
Soraya
S
Saïdi
Eric
E
Haÿ
Johann
J
Photsavang
Caroline
C
Marty
Juliette
J
Sailland
Julie
J
Carnesecchi
Violaine
V
Tribollet
Bruno
B
Barenton
Christelle
C
Forcet
Marie-Christine
MC
Birling
Tania
T
Sorg
Olivier
O
Chassande
Martine
M
Cohen-Solal
Jean-Marc
JM
Vanacker
D000818:Animals; D019070:Cell Lineage; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000502:physiology*; D004967:Estrogens / Q000172:deficiency*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology*; D010024:Osteoporosis / Q000473:pathology / Q000503:physiopathology*; D011817:Rabbits
D047628:Estrogen Receptor alpha; D004967:Estrogens