Actions of calcipotriol (MC 903), a novel vitamin D3 analog, on human bone-derived cells: comparison with 1,25-dihydroxyvitamin D3.
The actions of a novel vitamin D3 analog calcipotriol (MC 903), on human bone-derived cells were compared to those of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Both calcipotriol and 1,25-(OH)2D3 inhibited the proliferation of human osteoblast-like cells in a dose-dependent manner (10(-10)-10(-6) M), an effect observed at different cell densities. Lower concentrations of either agent exerted no marked effect on the growth of the cells compared to untreated cultures. Calcipotriol and 1,25-(OH)2D3 were equipotent in stimulating the activity of alkaline phosphatase and the synthesis of osteocalcin in human osteoblast-like cells. The stimulation of alkaline phosphatase activity and osteocalcin synthesis by both compounds was evident by 24 h and was increased progressively up to 96 h in a dose-dependent manner over the concentration range of 10(-10)-10(-6) M. The increment in both proteins was dependent on cell density and was attenuated at higher cell densities. In contrast to these actions, neither calcipotriol nor 1,25-(OH)2D3 (10(-14)-10(-6) M) affected the synthesis of prostaglandin E2. These studies indicate that calcipotriol and 1,25-(OH)2D3 exhibit a similar spectrum of activity on human osteoblast-like cells in vitro.
Evans
D B
DB
Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, England.
Thavarajah
M
M
Binderup
L
L
Kanis
J A
JA
D000469:Alkaline Phosphatase / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism
D015675:Osteocalcin; C055085:calcipotriene; D000469:Alkaline Phosphatase; D002117:Calcitriol; D015232:Dinoprostone; D013936:Thymidine