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

新生鼠颅骨来源的MC3T3-G2/PA6细胞是脂肪细胞前基质细胞，在糖皮质激素刺激下分化为脂肪细胞。我们观察了α，25-二羟基维生素D_3[α，25(OH)_2D_3]对PA6细胞成脂的影响。当PA6细胞与地塞米松共培养时，脂肪细胞在第7天(融合后第3天)出现含油红色O阳性小滴，在第12天达到最大中性脂合成高峰。同时，加入10^~(-9)M的α，25(OH)_2D_3可完全阻断地塞米松诱导的中性脂合成。维生素D_3衍生物的量效关系研究表明，α，25(OH)_2D_3对PA6和24，25-二羟基维生素D_3中性脂合成的抑制作用依次最强。地塞米松可显著促进PA6细胞中[^&lt；14&gt；C]-乙酸甘油三酯的掺入。加入10^-lt；-9&gt；Mα，25(OH)_2D_3可显著抑制[^&lt；-9&gt；Mα，25(OH)_2D_3的掺入。无论是否加入地塞米松，α，25(OH)_2D_3均能显著增加[^&lt；14&gt；C]-乙酸对磷脂酰胆碱和磷脂酰乙醇胺的掺入。这些结果提示，1α，25(OH)2D3对骨髓基质细胞脂代谢的调节是通过受体介导的。

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.