Insulin-like growth factor-1 modulates steroid hormone effects on osteocalcin synthesis in human MG-63 osteosarcoma cells.
The 1,25-dihydroxyvitamin-D3-(calcitriol)-induced medium osteocalcin and cellular osteocalcin mRNA concentrations are increased in a dose-dependent and time-dependent manner by prior treatment of the human MG-63 osteosarcoma cells with insulin-like growth factor-I (IGF-I). In addition, IGF-I reverses the inhibitory effects of dexamethasone and enhances the effects of retinoic acid on osteocalcin synthesis. The stimulatory effect of IGF-I on osteocalcin synthesis is accompanied by stabilization of osteocalcin mRNA and a decrease of AP-1 binding to the osteocalcin promoter. The binding of the vitamin-D receptor (VDR) to its cognate response element is not affected by IGF-I. In contrast to its effects on osteocalcin synthesis, both baseline and calcitriol-stimulated alkaline phosphatase activities are decreased by IGF-I treatment. Furthermore, IGF-I has mitogenic effects on MG-63 cells. The proliferation of the cells and the levels of c-jun mRNA are greatly increased during IGF-I treatment. Calcitriol reduces or eliminates both these effects. The low concentrations of IGF-I used in this study suggest that IGF-I is an important normal regulator of the synthesis of osteocalcin, a bone calcium-binding protein participating in bone mineralization, by modulating the effects of steroid hormones on its synthesis.
Pirskanen
A
A
Department of Biochemistry & Biotechnology, A. I. Virtanen Institute, University of Kuopio, Finland.
Jääskeläinen
T
T
Mäenpää
P H
PH
D000469:Alkaline Phosphatase / Q000378:metabolism; D001345:Autoradiography; D001483:Base Sequence; D002117:Calcitriol / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000096:biosynthesis* / Q000235:genetics; D012516:Osteosarcoma / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D000469:Alkaline Phosphatase; D002117:Calcitriol