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

M. Fernandez-Cancio, C. Esteban, A. Carrascosa, N. Toran, P. Andaluz, L. Audi

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16 Citations (Scopus)

Abstract

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 3H-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 dose-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, COL2A1 and aggrecan, and that their expression was regulated by Dx and IGF-I. Among IGFs, IGF-I and not IGF-II expression was demonstrated to be down-regulated by GCs whereas IGF-I expression was up-regulated by itself. © 2008 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)497-505
JournalGrowth Hormone and IGF Research
Volume18
Issue number6
DOIs
Publication statusPublished - 1 Dec 2008

Keywords

  • Dexamethasone
  • Gene expression
  • Human growth plate chondrocytes
  • IGF-I
  • Mifepristone

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