Role of vitamin D_3 on differentiation of bone marrow-derived stromal cells.

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MC3T3-G2/PA6 cells established from newborn mouse calvaria are preadipocytic stromal cells, which differentiate into adipocytes in response to glucocorticoids. We examined the effects of lalpha, 25-dihydroxyvitamin D_3 [lalpha, 25(OH) _2D_3] on adipgenesis in PA6 cells. When PA6 cells were cultured with 10^<-8> M dexamethasone, adipocytes contatining oil red O-positive droplets first appeared on day 7 (3 days after confluence was attained) and the maximal synthesis of neutral lipids occurred on day 12.Simultanieous addition of lalpha, 25(OH) _2D_3 at 10^<-9> M completely blocked this dexamethasone-induced neutral lipid synthesis throughout the 14-day culture period. Dose-response studies of vitamin D_3 derivatives showed that lalpha, 25(OH) _2D_3 was the most potent in inhibiting neutral lipid synthesis in PA6 and 24, 25-dihydroxyvitamin D_3, in that order. Dexamethasone greatly enhanced incorporation of [^<14>C]-acetic acid into triglycerol in PA6 cells. The incorporation was markedly inhibited by the addition of 10^<-9> M lalpha, 25(OH)_2D_3. Instead, lalpha, 25(OH) _2D_3 greatly increased incorporation of [^<14>C]-acetic acid into phospholipids, such as phosphatidylcholine and phosphatidylthanolamine, irrespective of the presence or absence of dexamethasone. These results suggest that 1alpha, 25(OH) _2D_3 modulation of lipid metabolism in bone marrow stromal cells is receptor mediated.