Affinity of MC 903 for 1,25-dihydroxyvitamin D receptor and its effects on the synthesis of osteocalcin in human osteosarcoma cells.
MC 903 is a new structural analog of the naturally occurring, biologically active 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. MC 903 and 1,25(OH)2D3 have shown similar receptor binding properties and comparable effects on leukemic cell differentiation. However, MC 903 is at least 100 times less potent in influencing calcium metabolism than 1,25(OH)2D3. We have therefore studied, how MC 903 competes for the binding sites of 1,25(OH)2D3, influences the 1,25(OH)2D3 induced synthesis of the most abundant bone non-collagenous protein, osteocalcin, and induces the activity of alkaline phosphatase in MG-63 human osteosarcoma cells. We found that the new compound binds to 1,25(OH)2D3 receptors and regulates receptor mRNA levels essentially like the natural ligand. Our results also indicate that MC 903 induces the synthesis of osteocalcin and the activity of alkaline phosphatase in MG-63 cells through a receptor-mediated process almost identically with 1,25(OH)2D3. Growth of the MG-63 cells was inhibited slightly more with MC 903 than with 1,25(OH)2D3.
Valaja
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Department of Biochemistry and Biotechnology, University of Kuopio, Finland.
Mahonen
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Pirskanen
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Mäenpää
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PH
D000469:Alkaline Phosphatase / Q000378:metabolism; D001667:Binding, Competitive; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D015675:Osteocalcin / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D015675:Osteocalcin; C055085:calcipotriene; D000469:Alkaline Phosphatase; D002117:Calcitriol