INSULIN-LIKE GROWTH FACTOR-I MODULATES STEROID-HORMONE EFFECTS ON OSTEOCALCIN SYNTHESIS IN HUMAN MG-63 OSTEOSARCOMA CELLS

Citation
A. Pirskanen et al., INSULIN-LIKE GROWTH FACTOR-I MODULATES STEROID-HORMONE EFFECTS ON OSTEOCALCIN SYNTHESIS IN HUMAN MG-63 OSTEOSARCOMA CELLS, European journal of biochemistry, 218(3), 1993, pp. 883-891
Citations number
46
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
ISSN journal
0014-2956
Volume
218
Issue
3
Year of publication
1993
Pages
883 - 891
Database
ISI
SICI code
0014-2956(1993)218:3<883:IGFMSE>2.0.ZU;2-V
Abstract
The 1,25-dihydroxyvitamin-D3-(calcitriol)-induced medium osteocalcin a nd cellular osteocalcin mRNA concentrations are increased in a dose-de pendent and time-dependent manner by prior treatment of the human MG-6 3 osteosarcoma cells with insulin-like growth factor-I (IGF-I). In add ition, IGF-I reverses the inhibitory,effects of dexamethasone and enha nces the effects of retinoic acid on osteocalcin synthesis. The stimul atory effect of IGF-I on osteocalcin synthesis is accompanied by stabi lization of osteocalcin mRNA and a decrease of AP-1 binding to the ost eocalcin 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-stimula ted alkaline phosphatase activities are decreased by IGF-I treatment. Furthermore, IGF-I has mitogenic effects on MG-63 cells. The prolifera tion of the cells and the levels of c-jun mRNA are greatly increased d uring IGF-I treatment. Calcitriol reduces or eliminates both these eff ects. 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.