INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1 EXPRESSION IN CULTURED HUMAN BONE-CELLS - REGULATION BY INSULIN AND GLUCOCORTICOID

Insulin-like growth factors (IGFs) and their specific regulatory bindi ng proteins (IGFBPs) are postulated to play a key role in bone metabol ism. To date, IGFBP-2 through -6 have been characterized in bone cell systems. In this study we focused on IGFBP-1. Primary cultures of norm al human osteoblasts derived from trabecular bone (hOB cells) expresse d low levels of IGFBP-1 messenger RNA (mRNA), as determined by Norther n analyses. Treatment of hOB cells with 1 mu M cortisol or 100 nM dexa methasone for 20 h stimulated IGFBP-1 mRNA expression 5-fold and incre ased levels of immunoassayable IGFBP-1 in the conditioned medium 3-fol d. Estradiol and progesterone had no effect. IGFBP-1 expression was no t observed in U-2, TE-85, or MG-63 human osteosarcoma cell lines or in normal human fibroblasts. Insulin (1-100 nM) potently inhibited both basal and glucocorticoid-stimulated IGFBP-1 expression in hOB cells. I nsulin had little or no effect on steady state levels of the other IGF BP mRNA. A monoclonal antibody to the insulin receptor blocked insulin binding to insulin receptors and completely prevented insulin-induced suppression of IGFBP-1. In summary, we have documented IGFBP-1 mRNA a nd protein expression in normal nontransformed human osteoblastic cell s. This expression was stimulated by glucocorticoids and inhibited by insulin in a manner similar to IGFBP-1 regulation in hepatocytes. Insu lin acts through insulin receptors on hOB cells. We postulate that IGF BP-1 produced by osteoblasts in vivo can modulate local actions of IGF on bone formation in response to changes in glucocorticoid and insuli n concentrations.