Activation of the hypoxia-inducible factor-1α pathway accelerates bone regeneration

Jan 11, 2008Proceedings of the National Academy of Sciences of the United States of America

Turning on the low-oxygen response speeds up bone healing

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Abstract

Mice lacking pVHL in osteoblasts showed increased vascularity and produced more bone during distraction osteogenesis.

  • The HIF-1alpha pathway is activated during bone repair and is crucial for normal skeletal development.
  • Mice without HIF-1alpha in osteoblasts experienced impaired blood vessel formation and bone healing.
  • Increased bone regeneration in pVHL mutants was dependent on vascular endothelial growth factor (VEGF).
  • Administration of small-molecule inhibitors that stabilize HIF/VEGF enhanced blood vessel formation in cell cultures.
  • One small molecule, DFO, significantly improved blood vessel formation and bone regeneration when applied in vivo.

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