Activation of the human osteocalcin gene by 24R,25-dihydroxyvitamin D3 occurs through the vitamin D receptor and the vitamin D-responsive element.
1 alpha-25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], together with vitamin D receptor (VDR), directly activates human osteocalcin (hOC) gene expression through a vitamin D-responsive element (VDRE) located in the promoter of the hOC gene. We investigated the effect of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] on the regulation of the hOC gene promoter and compared it with that of 1 alpha,25(OH)2D3. 24R,25(OH)2D3 did not activate the natural promoter in VDR-negative CV-1 cells. 24R,25(OH)2D3, however, induced the activation of this promoter following cotransfection with an hVDR expression vector. In VDR-positive MC3T3-E1 cells, 24R,25(OH)2D3 activated not only the natural hOC promoter but also a chimeric promoter composed of a synthetic hOC VDRE sequence linked to the thymidine kinase promoter. In combination with 1 alpha-25(OH)2D3, 24R,25(OH)2D3 did not exhibit any antagonist activity on the hOC promoter. These results suggest that under conditions of high 24R,25(OH)2D3 levels in vivo, this metabolite of vitamin D3 may activate hOC gene expression through receptor mechanisms identical to that for 1 alpha,25(OH)2D3.
Uchida
M
M
Department of Pediatrics and Cell Biology, Baylor College of Medicine, Houston, Texas.
Ozono
K
K
Pike
J W
JW
D000818:Animals; D001483:Base Sequence; D002117:Calcitriol / Q000494:pharmacology; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D015675:Osteocalcin / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000187:drug effects / Q000235:genetics*; D014162:Transfection
D018167:Receptors, Calcitriol; D015675:Osteocalcin; D002762:Cholecalciferol; D002117:Calcitriol