DEHYDROEPIANDROSTERONE (DHEA) AND DHEA-S INTERACT WITH 1,25-DIHYDROXYVITAMIN D-3 (1,25(OH)(2)D-3) 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 regul ation of bone mass. In this study, we examined whether DHEA/DHEA-S are capable of directly affecting bone cell proliferation and differentia tion, and compared this with the effects of, and interaction with, the established bone cell modulating steroid, 1,25-dihydroxyvitamin D-3 ( 1,25(OH)(2)D-3). Two in vitro models of human osteoblastic cells were used, viz. MG63 osteosarcoma cell line and normal primary osteoblastli ke 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 i n conjunction with 1,25(OH)(2)D-3 resulted in enhancement of specific ALP activity. Moreover, 1,25(OH)(2)D-3-induced osteocalcin production was potentiated by the adrenal steroids in both cell models, DHEA-S pr oved 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)(2 )D-3-induced changes in bone cells, suggesting a distinctive role for these steroids in the regulation of bone metabolism.