Dehydroepiandrosterone (DHEA) and DHEA-S interact with 1,25-dihydroxyvitamin D 3 (1,25(OH) 2D 3) to stimulate human osteoblastic cell differentiation

Abstract

DHEA, an adrenocortical steroid, and its sulfate derivative (DHEA-S), have been implicated in many biological functions, including the regulation of bone mass. In this study, we examined whether DHEA/DHEA-S are capable of directly affecting bone cell proliferation and differentiation, and compared this with the effects of, and interaction with, the established bone cell modulating steroid, 1,25-dihydroxyvitamin D 3 (1,25(OH) 2D 3). Two in vitro models of human osteoblastic cells were used, viz. MG63 osteosarcoma cell line and normal primary osteoblast-like cells (HOB). Our results show that DHEA and DHEA-S failed on their own to exert direct, independent significant effects on the growth and differentiation of human osteoblastic cells, but treating the cells in conjunction with 1,25(OH) 2D 3 resulted in enhancement of specific AIP activity. Moreover, 1,25(OH) 2D 3-induced osteocalcin production was potentiated by the adrenal steroids in both cell models. DHEA-S proved in general to be more potent than DHEA. In conclusion, this study shows that the effects of DHEA/DHEA-S on osteoblastic cell growth and differentiation are likely to be mediated via an effect on 1,25(OH) 2D 3-induced changes in bone cells, suggesting a distinctive role for these steroids in the regulation of bone metabolism.