Inhibitory effects of 9-cis and all-trans retinoic acid on 1,25(OH)2 vitamin D3 induced bone resorption

• 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.

Nyckelord

Bone resorption

9-Cis retinoic acid

All-Trans retinoic acid

1

25(OH)2 Vitamin D3

MEDICINE

MEDICIN

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ref (ämneskategori)

art (ämneskategori)