title: Absence of ERRalpha in female mice confers resistance to bone loss induced by age or estrogen-deficiency.
abstract: 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.
authors: 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.
authors: Catherine
authors: C
authors: Teyssier
authors: Marlène
authors: M
authors: Gallet
authors: Bénédicte
authors: B
authors: Rabier
authors: Laurent
authors: L
authors: Monfoulet
authors: Julien
authors: J
authors: Dine
authors: Claire
authors: C
authors: Macari
authors: Julie
authors: J
authors: Espallergues
authors: Béatrice
authors: B
authors: Horard
authors: Vincent
authors: V
authors: Giguère
authors: Martine
authors: M
authors: Cohen-Solal
authors: Olivier
authors: O
authors: Chassande
authors: Jean-Marc
authors: JM
authors: Vanacker
mesh_terms: 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
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D053495:Osteopontin