Absence of ERRalpha in female mice confers resistance to bone loss induced by age or estrogen-deficiency.
BACKGROUND
ERRalpha is an orphan member of the nuclear hormone receptor superfamily, which acts as a transcription factor and is involved in various metabolic processes. ERRalpha is also highly expressed in ossification zones during mouse development as well as in human bones and cell lines. Previous data have shown that this receptor up-modulates the expression of osteopontin, which acts as an inhibitor of bone mineralization and whose absence results in resistance to ovariectomy-induced bone loss. Altogether this suggests that ERRalpha may negatively regulate bone mass and could impact on bone fragility that occurs in the absence of estrogens.


RESULTS
In this report, we have determined the in vivo effect of ERRalpha on bone, using knock-out mice. Relative to wild type animals, female ERRalphaKO bones do not age and are resistant to bone loss induced by estrogen-withdrawal. Strikingly male ERRalphaKO mice are indistinguishable from their wild type counterparts, both at the unchallenged or gonadectomized state. Using primary cell cultures originating from ERRalphaKO bone marrow, we also show that ERRalpha acts as an inhibitor of osteoblast differentiation.


CONCLUSIONS
Down-regulating ERRalpha could thus be beneficial against osteoporosis.
Teyssier
Catherine
C
Institut de Génomique Fonctionnelle de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Ecole Normale Supérieure de Lyon, Lyon, France.
Gallet
Marlène
M
Rabier
Bénédicte
B
Monfoulet
Laurent
L
Dine
Julien
J
Macari
Claire
C
Espallergues
Julie
J
Horard
Béatrice
B
Giguère
Vincent
V
Cohen-Solal
Martine
M
Chassande
Olivier
O
Vanacker
Jean-Marc
JM
D000375:Aging; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053495:Osteopontin / Q000378:metabolism*; D014057:Tomography, X-Ray Computed / Q000379:methods
D047628:Estrogen Receptor alpha; D004967:Estrogens; D053495:Osteopontin