INHIBITORY EFFECTS OF 9-CIS AND ALL-TRANS-RETINOIC ACID ON 1,25(OH)(2) VITAMIN D-3-INDUCED BONE-RESORPTION

The effects of retinoic acid (RA), and calcitriol are mediated by spec ific nuclear receptors (RARs and VDR, respectively). Induction of RAR and VDR responsive elements in target genes requires a cofactor, the r etinoid-X-receptor (RXR), with its ligand 9-cis RA. We have previously demonstrated the expression of RARs and RXRs in osteoblasts, and here in investigated the effects of the retinoids all-trans RA and 9-cis RA alone and combined with calcitriol on bone resorption in vitro, measu red by Ca-45-release from prelabeled neonatal mouse calvarial bones. A ll-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 calcitri ol (1 pM). The findings are compatible with a physiological role for r etinoids in bone metabolism.