Action of 1,25-dihydroxyvitamin D3 on phospholipid metabolism of human bone cells in culture

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Abstract
It has recently been proposed that the action of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on bone metabolism may be mediated by changes in phospholipid metabolism. The effects of vitamin D metabolites on the incorporation of radiolabelled precursors into corresponding phospholipid classes were investigated using cells arising from cultured explants of normal human bone with osteoblast-like characteristics. Treatment with 1,25-(OH)2D3 increased the incorporation of serine, measured as the ratio of [3H]serine in phosphatidylserine (PS) to [14C]ethanolamine in phosphatidylethanolamine (PE), in a time- and dose-dependent manner. The maximum effect on PS/PE of 141·6 ± 5·9% over control (P = 0·022) was observed at a dose of 0·1 nmol 1,25-(OH)2D3/l, maintained for 24 h. Incubations with 25-hydroxyvitamin D3 (0·1 μmol/l) and 24,25-dihydroxyvitamin D3 (10 nmol/l) had no effect. Supraphysiological doses (0·1 μmol/l) of 1,24,25- and 1,25,26-trihydroxyvitamin D3 showed similar effects to those of 1,25-(OH)2D3, emphasizing the importance of 1α-hydroxylation. Incorporation of [14C]choline into phosphatidylcholine, calculated as a ratio to PE, was not affected by treatment with vitamin D metabolites. However, [3H]inositol uptake into phosphatidylinositol was almost doubled when compared with control uptake within 2 h of treatment with 1,25-(OH)2D3 (0·1 μmol/l). This may be of relevance, considering the importance of phosphoinositide metabolism in influencing the intracellular calcium concentration. These results support a role for 1,25-(OH)2D3 in the modulation of phospholipid metabolism in human bone cells, which in turn may be involved in the action of 1,25-(OH)2D3 in bone mineralization. J. Endocr. (1988) 116,435–441