1,25-Dihydroxyvitamin D3 and human bone-derived cells in vitro: effects on alkaline phosphatase, type I collagen and proliferation.
1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], but not 24,25-(OH)2D3 stimulates the alkaline phosphatase activity of cultured human bone cell populations. The stimulatory effect of the sterol was dose dependent (10(-10)-10(-7) M), evident by 24 h, and observed over a range of cell densities. Analysis of the radiolabeled collagens synthesised by human bone cell cultures indicated the synthesis of predominantly type I collagen. In the presence of 1,25-(OH)2D3, but not 24,25-(OH)2D3, there was a dose-dependent (10(-11)-10(-9) M) increase in radiolabeled proline incorporation into collagenase-digestible protein and in the amount of collagen synthesized, expressed as a percentage of the total protein synthesis. The effect of 1,25-(OH)2D3 was observed over a range of cell densities and appeared to be specific for the synthesis of type I collagen. The stimulatory effect of 1,25-(OH)2D3 on alkaline phosphatase activity and the increase in proline incorporation into collagenase-digestible protein were accompanied by a dose-dependent (5 X 10(-11) to 5 X 10(-8) M) inhibition of bone cell proliferation. These findings suggest that 1,25-(OH)2D3 is an important modulator of the growth and differentiation of human bone cells in vitro. They are also consistent with the possibility that 1,25-(OH)2D3 has direct effects on bone formation in vivo.
D015650:24,25-Dihydroxyvitamin D 3; D000469:Alkaline Phosphatase / Q000378:metabolism*; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D004100:Dihydroxycholecalciferols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans
D004100:Dihydroxycholecalciferols; D015650:24,25-Dihydroxyvitamin D 3; D003094:Collagen; D000469:Alkaline Phosphatase; D002117:Calcitriol