1 alpha,25-dihydroxyvitamin D3 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 1 alpha,25-dihydroxyvitamin D3[1 alpha,25(OH)2D3] on adipogenesis in PA6 cells. When 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 1 alpha,25(OH)2D3 at 10(-9)M completely blocked this dexamethasone-induced neutral lipid synthesis throughout the 14-day culture period. Dose-response studies of vitamin D3 derivatives showed that 1 alpha,25(OH)2D3 was the most potent in inhibiting neutral lipid synthesis in PA6 cells, followed by 1 alpha-hydroxyvitamin D3, 25-hydroxyvitamin D3, and 24R,25-dihydroxyvitamin D3, in that order. Dexamethasone greatly enhanced incorporation of [14C]-acetic acid into triacylglycerol in PA6 cells. The incorporation was markedly inhibited by the addition of 10(-9) M 1 alpha,25(OH)2D3. Instead, 1 alpha,25(OH)2D3 greatly increased incorporation of [14C]-acetic acid into phospholipids, such as phosphatidylcholine and phosphatidylethanolamine, irrespective of the presence or absence of dexamethasone. These results suggest that 1 alpha,25(OH)2D3 modulation of lipid metabolism in bone marrow stromal cells is receptor mediated.
Shionome
M
M
Department of Periodontics, School of Dentistry, Showa University, Tokyo, Japan.
Shinki
T
T
Takahashi
N
N
Hasegawa
K
K
Suda
T
T
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010743:Phospholipids / Q000032:analysis; D014280:Triglycerides / Q000032:analysis
D010743:Phospholipids; D014280:Triglycerides; D003907:Dexamethasone; D002117:Calcitriol