Dehydroepiandrosterone (DHEA) and DHEA-S interact with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to stimulate human osteoblastic cell differentiation

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 D3 (1,25(OH)2D3). 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)2D3 resulted in enhancement of specific A1P activity. Moreover, 1,25(OH)2D3-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)2D3-induced changes in bone cells, suggesting a distinctive role for these steroids in the regulation of bone metabolism.