Fiche publication
Date publication
décembre 2001
Journal
Endocrinology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
,
Dr KREZEL Wojciech
Tous les auteurs :
Yagishita N, Yamamoto Y, Yoshizawa T, Sekine K, Uematsu Y, Murayama H, Nagai Y, Krezel W, Chambon P, Matsumoto T, Kato S
Lien Pubmed
Résumé
VDR forms heterodimers with one of three RXRs, RXR alpha, RXR beta, and RXR gamma, and it is thought that RXR ligands can also modulate the trans-activation function of VDR/RXR heterodimers. In the present study we generated VDR/RXR gamma double null mutant mice to examine the convergent actions of vitamin D and vitamin A signaling and to explore the possibility of a functionally redundant VDR. Although RXR gamma(-/-) mice exhibited no overt abnormalities, VDR(-/-)/RXR gamma(-/-) mice appeared similar to VDR(-/-) mice, showing features typical of vitamin D-dependent rickets type II, including growth retardation, impaired bone formation, hypocalcemia, and alopecia. However, compared to VDR(-/-) mice, growth plate development in VDR(-/-)/RXR gamma(-/-) mutant mice was more severely impaired. Normalizing mineral ion homeostasis through dietary supplementation with high calcium and phosphorous effectively prevented rachitic abnormalities, except for disarranged growth plates in VDR(-/-)/RXR gamma(-/-) mutant mice, and alopecia in both VDR(-/-) and VDR(-/-)/RXR gamma(-/-) mutant mice. Histological analysis of VDR(-/-)/RXR gamma(-/-) growth plates revealed that development of the hypertrophic chondrocytes was selectively impaired. Thus, our findings indicated that the combined actions of VDR- and RXR gamma-mediated signals are essential for the normal development of growth plate chondrocytes, and raised the possibility that a functionally redundant VDR is present on chondrocytes as a heterodimer with RXR gamma.
Mots clés
Animals, Apoptosis, physiology, Bone and Bones, pathology, Chondrocytes, pathology, Diet, Growth Plate, growth & development, Homeostasis, Hypertrophy, Mice, Mice, Knockout, genetics, Minerals, administration & dosage, Osteoclasts, physiology, Phenotype, Receptors, Calcitriol, deficiency, Receptors, Retinoic Acid, deficiency, Retinoid X Receptors, Transcription Factors, deficiency
Référence
Endocrinology. 2001 Dec;142(12):5332-41
