All-trans retinoic acid inhibits dexamethasone-induced ALP activity and mineralization in human osteoblastic cell line SV HFO

Abstract

We have recently established a human osteoblastic cell line (SV-HFO) in a culture system, in which the cells are mineralized by treatment with dexamethasone (Dex). Using this system, we examined the effects of all trans-retinoic acid (RA) on the mineralization of the cells. RA inhibited the mineralization, coincident with the inhibition of alkaline phosphatase (ALP). On the other hand, RA induced osteocalcin secretion and had no effect on the expression of the other osteoblastic markers such as type I collagen and osteonectin. To further clarify the mechanism of inhibition of mineralization by RA, we used the retinoic acid receptor (RAR)α-selective (Am80), β-selective (CD2019) and γ-selective (CD437) agonists instead of RA. RARα- and RARβ-selective agonists inhibited the mineralization and ALP activity of the cells, while the RARγ-selective agonist had no such effects. On the other hand, the RARγ-selective agonist induced osteocalcin secretion, but RARα- and RARβ-selective agonists had no effect on osteocalcin secretion. These results suggested that the inhibitory effect of RA on the mineralization of human osteoblasts is mediated by the activation of RARα and/or RARβ and that RARγ preferentially regulates the expression of osteocalcin without influence on mineralization.