Stimulatory effects of insulin-like growth factor-I on growth plate chondrogenesis are mediated by nuclear factor-kappaB p65

J Biol Chem. 2008 Dec 5;283(49):34037-44. doi: 10.1074/jbc.M803754200. Epub 2008 Oct 15.

Abstract

Insulin-like growth factor-I (IGF-I) is an important regulator of endochondral ossification. However, little is known about the signaling pathways activated by IGF-I in growth plate chondrocytes. We have previously shown that NF-kappaB-p65 facilitates growth plate chondrogenesis. In this study, we first cultured rat metatarsal bones with IGF-I and/or pyrrolidine dithiocarbamate (PDTC), a known NF-kappaB inhibitor. The IGF-I-mediated stimulation of metatarsal growth and growth plate chondrogenesis was neutralized by PDTC. In rat growth plate chondrocytes, IGF-I induced NF-kappaB-p65 nuclear translocation. The inhibition of NF-kappaB-p65 expression and activity (by p65 short interfering RNA and PDTC, respectively) in chondrocytes reversed the IGF-I-mediated induction of cell proliferation and differentiation and the IGF-I-mediated prevention of cell apoptosis. Moreover, the inhibition of the phosphatidylinositol 3-kinase and Akt abolished the effects of IGF-I on NF-kappaB activation. In conclusion, our findings indicate that IGF-I stimulates growth plate chondrogenesis by activating NF-kappaB-p65 in chondrocytes.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Chondrocytes / metabolism
  • Chondrogenesis / drug effects*
  • Collagen Type X / chemistry
  • Growth Plate / growth & development*
  • Insulin-Like Growth Factor I / metabolism*
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Transcription Factor RelA / chemistry
  • Transcription Factor RelA / physiology*

Substances

  • Collagen Type X
  • NF-kappa B
  • Transcription Factor RelA
  • Insulin-Like Growth Factor I
  • Phosphatidylinositol 3-Kinases