Role of HIF-1α in skeletal development

Chao Wan, Jin Shao, Shawn R. Gilbert, Ryan C. Riddle, Fanxin Long, Randall S. Johnson, Ernestina Schipani, Thomas L. Clemens

Research output: Chapter in Book/Report/Conference proceedingConference contribution

102 Scopus citations


Angiogenesis and osteogenesis are tightly coupled during bone development and regeneration. Mesenchymal cells in the developing stroma elicit angiogenic signals to recruit new blood vessels into bone. Reciprocal signals, likely emanating from the incoming vascular endothelium, stimulate mesenchymal cell specification through additional interactions with cells within the vascular stem cell niche. The hypoxia-inducible factor-1 alpha (HIF-1) pathway has been identified as a key component in this process. We demonstrated that overexpression of HIF-1 in mature osteoblasts through disruption of the von Hippel-Lindau protein profoundly increases angiogenesis and osteogenesis; these processes appear to be coupled by cell nonautonomous mechanisms involving the action of vascular endothelial growth factor (VEGF) on the endothelial cells. The same occurred in the model of injury-mediated bone regeneration (distraction osteogenesis). Surprisingly, manipulation of HIF-1 does not influence angiogenesis of the skull bones, where earlier activation of HIF-1 in the condensing mesenchyme upregulates osterix during cranial bone formation.

Original languageEnglish (US)
Title of host publicationSkeletal Biology and Medicine
PublisherBlackwell Publishing Inc.
Number of pages5
ISBN (Print)9781573317856
StatePublished - Mar 2010
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632


  • Angiogenesis
  • Hypoxia-inducible factor
  • Knockout mice
  • Osteoblasts

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science


Dive into the research topics of 'Role of HIF-1α in skeletal development'. Together they form a unique fingerprint.

Cite this