Modulating Effect of Estrogen on the Fluoride-stimulated Osteoblastic Activities

다국어 초록 (Multilingual Abstract)

Combination therapy of fluoride (F) and estrogen in osteoporosis patients has been shown to induce greater increase in axial bone mass and decrease in vertebral fracture rate than fluoride or estrogen alone. Therefore, there is a possibility that when estrogen is combined with F for osteoporosis therapy, estrogen may have modulating effects on osteogenic action of F in addition to its bone resorption inhibitory effect. To test this hypothesis, the present study aimed to investigate whether estrogen enhance the effect of F on cell proliferation, differentiation, and mineralized nodule formation in fetal rat calvarial osteoblastic cells in vitro. In this study, estrogen (10^-10, 10^-8M) alone did not significantly affect osteoblastic cell proliferation, differentiation, and mineralized nodule formation, though it slightly increased alkaline phosphatase activity. F enhanced mineralized nodule formation in dose-dependent manner and augmented the expression of osteoblast differentiation marker genes such as type I collagen, alkaline phosphatase, osteopontin and osteocalcin. In addition, F also enhanced cell proliferation. Although F alone increased osteogenic activity, those effects were more conspicuous at higher concentration of F which is higher than therapeutically active serum concentration. While estrogen alone did not significantly affect osteoblast activity, simultaneous addition with F further enhanced all the osteogenic parameters examined and those enhancing effects were more remarkable in the presence of lower concentration of F (1, 10μM). Therefore these findings suggest that estrogen have modulating effects so that F is more osteogenic in vitro in the presence of estrogen.