IGF-I and not IGF-II expression is regulated by glucocorticoids in human fetal epiphyseal chondrocytes

Objective: TO elucidate the involvement of IGF axis components and the potential effects Of glucocorticoids (GCs) in human fetal growth regulation. Design: We studied the regulation by dexamethasone (Dx) and IGF-I of proliferation and IGF axis components and matrix protein gene expression in human fetal epiphyseal chondrocytes. Results: High Dx concentration (10(-7)-10(-6) M) inhibited H-3-thymidine incorporation, mifepristone (MF) 10(-6) M limited inhibition by Dx, and IGF-I (100 ng/ml) significantly stimulated proliferation and completely opposed inhibition by Dx. Dx close-dependently (10(-9)-10(-6) M) inhibited IGF-I, IGFBP3 and SOX9 gene expression and expression of GHR, COL2A1 and aggrecan from 10(-7) M to 10(-6) M whereas it stimulated IGF-IR expression. By contrast, Dx had no significant effect on IGF-II expression. IGF-I stimulated IGF-I, IGFBP3, SOX9, COL2A1 and aggrecan expression whereas it inhibited IGF-IR expression. IGF-I could oppose COL2A1 and aggrecan gene expression inhibition by Dx. Conclusions: We demonstrated for the first time by real-time quantitative PCR that human fetal epiphyseal chondrocytes expressed IGF axis components, Such as IGF-I, IGF-II, IGFBP3, IGF-IR and GHR and SOX9, COL2AI and aggrecan, and that their expression was regulated by Dx and IGF-I. Among IGR, IGF-I and not IGF-II expression was demonstrated to be down-regulated by GCs whereas IGF-I expression was up-regulated by itself. (C) 2008 Elsevier Ltd. All rights reserved.