Role of HIF‐1α in skeletal development
- 5 April 2010
- journal article
- review article
- Published by Wiley in Annals of the New York Academy of Sciences
- Vol. 1192 (1), 322-326
- https://doi.org/10.1111/j.1749-6632.2009.05238.x
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.Keywords
This publication has 38 references indexed in Scilit:
- Role of hypoxia-inducible factor-1α in angiogenic–osteogenic couplingJournal of Molecular Medicine, 2009
- Activation of the hypoxia-inducible factor-1α pathway accelerates bone regenerationProceedings of the National Academy of Sciences, 2008
- The hypoxia-inducible factor α pathway couples angiogenesis to osteogenesis during skeletal developmentJCI Insight, 2007
- Hif-1α regulates differentiation of limb bud mesenchyme and joint developmentThe Journal of cell biology, 2007
- Distinct osteogenic mechanisms of bones of distinct originsJournal of Orthopaedic Science, 2004
- Regulation of hypoxia-inducible factor-1α by cyclical mechanical stretch in rat vascular smooth muscle cellsClinical Science, 2003
- Hypoxia-Induced Gene Expression Occurs Solely through the Action of Hypoxia-Inducible Factor 1α (HIF-1α): Role of Cytoplasmic Trapping of HIF-2αMolecular and Cellular Biology, 2003
- Hypoxia-Inducible Factor-1α/Vascular Endothelial Growth Factor Pathway for Adventitial Vasa Vasorum Formation in Hypertensive Rat AortaHypertension, 2002
- Regulation of Mammalian O2Homeostasis by Hypoxia-Inducible Factor 1Annual Review of Cell and Developmental Biology, 1999
- Transactivation and Inhibitory Domains of Hypoxia-inducible Factor 1αJournal of Biological Chemistry, 1997