title: Inhibitory effects of 9-cis and all-trans retinoic acid on 1,25(OH)2 vitamin D3-induced bone resorption.
abstract: The effects of retinoic acid (RA), and calcitriol are mediated by specific nuclear receptors (RARs and VDR, respectively). Induction of RAR and VDR responsive elements in target genes requires a cofactor, the retinoid-X-receptor (RXR), with its ligand 9-cis RA. We have previously demonstrated the expression of RARs and RXRs in osteoblasts, and herein investigated the effects of the retinoids all-trans RA and 9-cis RA alone and combined with calcitriol on bone resorption in vitro, measured by 45Ca-release from prelabeled neonatal mouse calvarial bones. All-trans RA and 9-cis RA were powerful stimulators of bone resorption and essentially equipotent. At threshold concentrations (1 nM) both 9-cis RA and at-RA markedly inhibited the resorption induced by calcitriol (1 pM). The findings are compatible with a physiological role for retinoids in bone metabolism.
authors.affiliation: Department of Internal Medicine, University Hospital, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Kindmark
authors.forename: H
authors.initials: H
authors.lastname: Melhus
authors.forename: S
authors.initials: S
authors.lastname: Ljunghall
authors.forename: O
authors.initials: O
authors.lastname: Ljunggren
mesh_terms: D000818:Animals; D001862:Bone Resorption; D001842:Bone and Bones / Q000187:drug effects*; D002117:Calcitriol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D014212:Tretinoin; D002117:Calcitriol