Several types specific insulin-like growth factor binding proteins (IGFBPs) are produced by peripheral tissue-derived cells and they modulate the functions of insulin-like growth factors. In this study, both the secretion of IGFBP-3 from a human osteosarcoma cell line MG63 and effects of 1, 25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) on the production of IGFBP-3 were investigated. The β subunit of IGFBP-3 was detected immunocytochemically in the perinuclear cytoplasm of MG63 cells. Immunoblotting and SDS-PAGE analysis revealed that both 140-150KD MW entire molecules and 40-60KD MW β subinit molecules of IGFBP-3 were present in cell-conditionel media. 1,25-(OH)(2)D(3) stimulated the production of the IGFBP-3 molecule by MG63 cells. The concentration of IGFBP-3 conditioned media began to rise at 24 hours after the addtiton of 10(-9)M of 1,25-(OH)(2)D(3) and reached the peak level at 48 hours. Dose-dependent effects of 1,25-(OH)(2)D(3) were demonstrated. These findings show that MG63 produces IGFBP-3 and that 1,25-(OH)(2)D(3) stimulates the production of this protein. These findings suggest that the synergistic effects of 1,25-(OH)(2)D(3) on the action of IGF-I on osteoblastic cells may be modulated by locally produced IGFBP-3.
insulin-like growth factor binding protein 3
human osteosarcoma cell line MG63