Ca. Conover et al., INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1 EXPRESSION IN CULTURED HUMAN BONE-CELLS - REGULATION BY INSULIN AND GLUCOCORTICOID, Endocrinology, 137(8), 1996, pp. 3295-3301
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.