Runx2 Protein Stabilizes Hypoxia-inducible Factor-1α through Competition with von Hippel-Lindau Protein (pVHL) and Stimulates Angiogenesis in Growth Plate Hypertrophic Chondrocytes

Feb 22, 2012The Journal of biological chemistry

Runx2 protein helps stabilize low-oxygen response factor by competing with its regulator and promotes new blood vessel growth in bone growth cartilage cells

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Abstract

Runx2 caused the accumulation of HIF-1α protein in chondrocytes under normoxic conditions.

  • Runx2 increased the nuclear translocation of HIF-1α in cells coexpressing both proteins.
  • Runx2 interacted with HIF-1α at the oxygen-dependent degradation domain, inhibiting its ubiquitination.
  • Overexpression of Runx2 enhanced vascular endothelial growth factor (VEGF) promoter activity and protein secretion.
  • Runx2 significantly increased angiogenic activity in human umbilical vein endothelial cells in vitro.
  • In wild-type mice, HIF-1α and Runx2 were colocalized in hypertrophic chondrocytes expressing CD31 at embryonic day 15.5.
  • The expression of HIF-1α was reduced in areas of CD31 expression in Runx2(-/-) mice.

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