Glucocorticoid regulation of insulin-like growth factor-binding protein expression in normal human osteoblast-like...

Glucocorticoid (GC) modulates insulin-like growth factor (IGF) action in bone through mechanisms that are complex and not well understood. Because the family of IGF-binding proteins (IGFBP-1 through -6) is important in the regulation of IGF availability and bioactivity, we examined the effect of GC on IGFBP expression in normal human osteoblast-like (hOB) cells. As assessed by Western ligand blot, hOB cells release IGFBP-3, IGFBP-4, and a 31-kilodalton IGFBP, which appeared to be IGFBP-5. Northern analysis revealed that hOB cells express abundant IGFBP-3, IGFBP-4, IGFBP-5, and IGFBP-6 mRNA, with barely detectable IGFBP-1 mRNA. GC treatment resulted in time- and dose-dependent decreases in IGFBP-3, IGFBP-4, and 31-kilodalton IGFBP levels in culture medium, with corresponding decreases in IGFBP-3, IGFBP-4, and IGFBP-5 mRNA levels. In addition, GC treatment increased steady state levels of IGFBP-1 mRNA and did not alter IGFBP-6 mRNA levels. Although hOB cells secrete an acid-activated IGFBP-3 protease and an IGF-dependent IGFBP-4 protease, GC had little effect on these protease activities and did not alter degradation of the secreted IGFBPs. Our results indicate that GC has dramatic effects on IGFBP gene expression and suggest that differential regulation of IGFBPs by GC may modulate hOB cell responsiveness to IGFs.