1α,25‐Dihydroxyvitamin D 3 modulation in lipid metabolism in established bone marrow‐derived stromal cells, MC3T3‐G2/PA6

MC3T3‐G2/PA6 (PA6) cells established from newborn mouse calvaria are preadipocytic stromal cells, which differentiate into adipocytes in response to glucocorticoids. We examined the effects of 1α,25‐dihydroxyvitamin D 3 [1α,25(OH) 2 D 3 ] on adipogenesis in PA6 cells were cultured with 10 −8 M dexamethasone, adipocytes containing 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. Simultaneous addition of 1α,25(OH) 2 D 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 1α,25(OH) 2 D 3 was the most potent in inhibiting neutral lipid synthesis in PA6 cells, followed by 1α‐hydroxyvitamin D 3 , 25‐hydroxyvitamin D 3 and 24R,25‐dihydroxyvitamin D 3 , in that order. Dexamethasone greatly enhanced incorporation of [ 14 C]‐acetic acid into triacylglycerol in PA6 cells. The incorporation was markedly inhibited by the addition of 10 −9 M 1α,25(OH) 2 D 3 Instead, 1α,25(QH) 2 D 3 greatly increased incorporation of [ 14 C]‐acetic acid into phospholipids, such as phosphatidylcholine and phosphatidylethanolamine, irrespective of the presence or absence of dexamethasone. These results suggest that 1α,25(OH) 2 D 3 modulation of lipid metabolism in bone marrow stromal cells is receptor mediated.