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Cited by 173Bone Metabolism and DiseasesBone Tissue Engineering MaterialsAngiogenesis and VEGF in Cancer

Role of HIF‐1α in skeletal development

Open access
Wan, Chao, Shao, Jin, Gilbert, Shawn R., Riddle, Ryan C., Long, Fanxin, Johnson, Randall S., Schipani, Ernestina, Clemens, Thomas L.·2010·Annals of the New York Academy of Sciences
DOI 10.1111/j.1749-6632.2009.05238.xPMC PMC3047468
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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.

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  • The coding region of Hif1a contains a conserved sequence complementary to the miR-140-5p-G seed sequence.

    “The coding region of Hif1a that encodes a master transcription factor controlling hypoxic response27 contains a conserved sequence complementary to the miR-140-5p-G seed sequence.”

    From Gain-of-function mutation of microRNA-140 in human skeletal dysplasia (2019) · cites this paper as [27]

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Authors
Wan, C., Shao, J., Gilbert, S. R., Riddle, R. C., Long, F., Johnson, R. S., Schipani, E., & Clemens, T. L.
Affiliations
  • Johns Hopkins University (US)
  • Shanghai Jiao Tong University (CN)
  • University of Alabama at Birmingham (US)
  • Washington University in St. Louis (US)
  • University of California San Diego (US)
  • Harvard University (US)
Corresponding author
Wan, Chao
ORCID
Venue
Annals of the New York Academy of Sciences
Publisher
Wiley
Published
2010-04
Volume
1192
Issue
1
Pages
322-326
ISSN
  • 0077-8923 (ISSN-L)
  • 1749-6632
DOI
10.1111/j.1749-6632.2009.05238.x
PMC
PMC3047468
OpenAlex
W2024963081
Cited by
173
References
3
Citations by year
2026: 7 · 2025: 10 · 2024: 6 · 2023: 13 · 2022: 20 · 2021: 14 · 2020: 9 · 2019: 15 · 2018: 9 · 2017: 1 · 2016: 7 · 2015: 11 · 2014: 8 · 2013: 8 · 2012: 13
FWCI
1.15
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 4 d)
Locations
  • Annals of the New York Academy of Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR049410, AR049410, R01AR048191)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
HIF-1α, hypoxia-inducible factor, skeletal development, angiogenesis, bone formation, von Hippel-Lindau protein, osteoblasts, vascular endothelial growth factor, vascular endothelium, mesenchymal cells, distraction osteogenesis, bone regeneration, Osterix, non-cell-autonomous signaling
MeSH terms
Animals, Bone and Bones, Bone Development, Humans, Osteogenesis, Skull, Signal Transduction, Neovascularization, Physiologic, Hypoxia-Inducible Factor 1, alpha Subunit

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