1,25-Dihydroxyvitamin D3 and human bone-derived cells in vitro: effects on alkaline phosphatase, type I collagen and proliferation

• Published in: Endocrinology (Philadelphia) Vol. 119; no. 4; p. 1776
• Main Authors: Beresford, J N, Gallagher, J A, Russell, R G
• Format: Journal Article
• Language: English
• Published: United States 01-10-1986
• Subjects: 24,25-Dihydroxyvitamin D 3; Alkaline Phosphatase - metabolism; Bone and Bones - cytology; Bone and Bones - drug effects; Bone and Bones - metabolism; Calcitriol - pharmacology; Cell Division - drug effects; Cells, Cultured; Collagen - biosynthesis; Dihydroxycholecalciferols - pharmacology; Dose-Response Relationship, Drug; Humans
• ISSN: 0013-7227
• DOI: 10.1210/endo-119-4-1776

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.