Enhanced expression of vascular endothelial growth factor in human SaOS-2 osteoblast-like cells and murine osteoblasts induced by insulin-like growth factor I

Endocrinology. 1996 Jun;137(6):2262-8. doi: 10.1210/endo.137.6.8641174.


Formation of new capillaries, a critical component of tissue growth and repair, is a recognized process in the development, formation, and remodeling of bone. Vascular endothelial growth factor (VEGF), a potent angiogenic factor with specific mitogenic actions on endothelial cells, is produced in a regulated manner by many cell types, including osteoblasts. The aim of the present investigation was to test the hypothesis that insulin-like growth factor I (IGF-I), a known osteogenic factor, modulates VEGF expression in osteoblasts. In human SaOS-2 osteoblast-like cells, 10 nM IGF-I increased the abundance of VEGF messenger RNA (mRNA) by 4-fold above the control value at 2h, and the elevated levels of mRNA returned to near basal by 8 h. IGF-I stimulated VEGF mRNA levels at IGF-I concentrations as low as 1-2 nM. The stability of VEGF mRNA was not increased after IGF-I treatment, and actinomycin D abrogated the enhanced expression of VEGF mRNA by IGF-I, indicating that the action of IGF-I was probably mediated by a transcriptional mechanism. The induction of VEGF mRNA by IGF-I in SaOS-2 cells was associated with an increase in immunoreactive VEGF protein, as detected by immunoblot analysis. IGF-I also increased the expression of VEGF mRNA in primary murine osteoblasts, which confirmed that the actions of IGF-I were not unique to SaOS-2 cells. We conclude that IGF-I enhances osteoblast synthesis of VEGF, which may then act locally on endothelium to stimulate angiogenesis, an essential component of bone growth and remodeling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • Cell Line
  • Dactinomycin / pharmacology
  • Drug Stability
  • Endothelial Growth Factors / genetics*
  • Gene Expression / drug effects*
  • Humans
  • Insulin-Like Growth Factor I / pharmacology*
  • Lymphokines / genetics*
  • Mice
  • Osteoblasts / metabolism*
  • Protein Synthesis Inhibitors / pharmacology
  • RNA, Messenger / biosynthesis
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Lymphokines
  • Protein Synthesis Inhibitors
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Dactinomycin
  • Insulin-Like Growth Factor I