Retinoic acid stimulates 1,25-dihydroxyvitamin D3 binding in rat osteosarcoma cells.
Since several aspects of the effects of vitamin A and 1 alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on bone metabolism are quite similar, we examined the possibility that vitamin A effects on bone were mediated through the regulation of cytosolic 1,25-(OH)2D3 receptors. A clonal osteoblast-like cell line derived from rat osteosarcoma (ROS 17/2) was used as a model system. Vitamin A acid (retinoic acid) in concentrations ranging from 10(-8) to 10(-5) M was found to elicit a dose-dependent increase in 1,25-(OH)2D3 binding in these cells. This effect was maximal after 24 h, was independent of cell density, and was inhibited by actinomycin D (0.05-0.5 microgram/ml). The 1,25-(OH)2D3 binding macromolecule in cytosol preparations from both vehicle- and retinoic acid-treated cells had a sedimentation coefficient of 3.2 S and binding specificities for vitamin D3 metabolites in the order: 1,25-(OH)2D3 greater than 25-(OH)-D3 greater than 24,25-(OH)2D3. Sucrose density gradient analysis, vitamin D3 metabolite displacement studies, and saturation and Scatchard analyses all indicated that the specific increase in 1,25-(OH)2[3H]D3 binding in these cells was the result of a selective increase in the number of specific 1,25-(OH)2D3 receptors.
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D007700:Kinetics; D012516:Osteosarcoma / Q000378:metabolism*; D051381:Rats; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D014801:Vitamin A; D014212:Tretinoin; D002117:Calcitriol