Role of HIF-1α in skeletal development

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

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

Abstract

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 publicationAnnals of the New York Academy of Sciences
Pages322-326
Number of pages5
Volume1192
DOIs
StatePublished - Mar 2010

Publication series

NameAnnals of the New York Academy of Sciences
Volume1192
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Hypoxia-Inducible Factor 1
Bone
Osteogenesis
Bone Regeneration
Blood Vessels
Stem Cell Niche
Distraction Osteogenesis
Bone and Bones
Bone Development
Vascular Endothelium
Mesoderm
Osteoblasts
Skull
Cell Communication
Vascular Endothelial Growth Factor A
Endothelial cells
Blood vessels
Stem cells
Up-Regulation
Endothelial Cells

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Wan, C., Shao, J., Gilbert, S. R., Riddle, R., Long, F., Johnson, R. S., ... Clemens, T. (2010). Role of HIF-1α in skeletal development. In Annals of the New York Academy of Sciences (Vol. 1192, pp. 322-326). (Annals of the New York Academy of Sciences; Vol. 1192). https://doi.org/10.1111/j.1749-6632.2009.05238.x

Role of HIF-1α in skeletal development. / Wan, Chao; Shao, Jin; Gilbert, Shawn R.; Riddle, Ryan; Long, Fanxin; Johnson, Randall S.; Schipani, Ernestina; Clemens, Thomas.

Annals of the New York Academy of Sciences. Vol. 1192 2010. p. 322-326 (Annals of the New York Academy of Sciences; Vol. 1192).

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

Wan, C, Shao, J, Gilbert, SR, Riddle, R, Long, F, Johnson, RS, Schipani, E & Clemens, T 2010, Role of HIF-1α in skeletal development. in Annals of the New York Academy of Sciences. vol. 1192, Annals of the New York Academy of Sciences, vol. 1192, pp. 322-326. https://doi.org/10.1111/j.1749-6632.2009.05238.x
Wan C, Shao J, Gilbert SR, Riddle R, Long F, Johnson RS et al. Role of HIF-1α in skeletal development. In Annals of the New York Academy of Sciences. Vol. 1192. 2010. p. 322-326. (Annals of the New York Academy of Sciences). https://doi.org/10.1111/j.1749-6632.2009.05238.x
Wan, Chao ; Shao, Jin ; Gilbert, Shawn R. ; Riddle, Ryan ; Long, Fanxin ; Johnson, Randall S. ; Schipani, Ernestina ; Clemens, Thomas. / Role of HIF-1α in skeletal development. Annals of the New York Academy of Sciences. Vol. 1192 2010. pp. 322-326 (Annals of the New York Academy of Sciences).
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