REGULATION OF INSULIN-LIKE-GROWTH-FACTOR-I AND INSULIN-LIKE-GROWTH-FACTOR-II AND THEIR BINDING-PROTEINS IN HUMAN BONE-MARROW STROMAL CELLS BY DEXAMETHASONE

Glucocorticoids inhibit the proliferation, but induce the differentiat ion, of bone marrow stromal cells into osteoblast-like cells. The mech anisms, however, are still conjectural. Since insulin-like growth fact ors (IGFs) have profound effects on osteoblast growth and differentiat ion, it is possible that glucocorticoids exert their effects on bone m arrow stromal cells in part via regulation of IGFs. Therefore, we anal yzed the effects of dexamethasone (Dex) on the expression of IGF I and IGF II in cultured preosteoblastic normal human bone marrow stromal c ells (HBMSC). Whereas Dex decreased the concentration of IGF I in the conditioned medium since early in the treatment, the concentration of IGF II was increased progressively as culture period lengthened. As th e activities of IGF I and IGF II are regulated by the IGF binding prot eins (IGFBPs), we analyzed the effects of Dex on the expression of IGF BPs. Dex increased IGFBP-2 in a time-dependent manner. The increase in IGFBP-2, however, was only to the same extent as that of IGF II at mo st, depending on the length of treatment. Therefore, the increase in I GFBP-2 would dampen, but not eliminate, the increased IGF II activitie s. By contrast, Dex decreased IGFBP-3 levels, the latter increasing th e bioavailability of IGF II. Although IGFBP-4 mRNA levels were stimula ted by Dex, IGFBP-4 concentration in the conditioned medium was unchan ged as measured by RIA. IGFBP-5 and IGFBP-6 mRNA levels were decreased by Dex in a time-dependent fashion. IGFBP-5 protein level was also de creased 1-4 days after Dex treatment. IGFBP-1 mRNA was not detectable in HBMSC. These accumulated data indicate that Dex regulates IGF I and IGF II and their binding proteins differentially in normal human bone marrow stromal cells. The progressive increase in IGF II may contribu te to Dex-induced cell differentiation. J. Cell. Biochem. 71 :449-458, 1998. (C) 1998 Wiley-Liss, Inc.