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Review
. 2009 Jun;87(6):583-90.
doi: 10.1007/s00109-009-0477-9. Epub 2009 May 5.

Role of hypoxia-inducible factor-1alpha in angiogenic-osteogenic coupling

Ryan C Riddle  1 , Richa Khatri, Ernestina Schipani, Thomas L Clemens
Affiliations
Review

Role of hypoxia-inducible factor-1alpha in angiogenic-osteogenic coupling

Ryan C Riddle et al. J Mol Med (Berl). 2009 Jun.

Abstract

Angiogenesis and osteogenesis are tightly coupled during bone development and regeneration. The vasculature supplies oxygen to developing and regenerating bone and also delivers critical signals to the stroma that stimulate mesenchymal cell specification to promote bone formation. Recent studies suggest that the hypoxia-inducible factors (HIFs) are required for the initiation of the angiogenic-osteogenic cascade. Genetic manipulation of individual components of the HIF/vascular endothelial growth factor (VEGF) pathway in mice has provided clues to how coupling is achieved. In this article, we review the current understanding of the cellular and molecular mechanisms responsible for angiogenic-osteogenic coupling. We also briefly discuss the therapeutic manipulation of HIF and VEGF in skeletal repair. Such discoveries suggest promising approaches for the development of novel therapies to improve bone accretion and repair.

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Figures

Fig. 1
Fig. 1
Model for angiogenic–osteogenic coupling in bone. The expression of HIF-1α by resident osteoblasts (OBs) during bone formation and repair leads to the upregulation of VEGF and other angiogenic signals. VEGF may stimulate bone formation via a cell nonautonomous mechanism (solid lines) that involves vascular invasion. Blood vessels direct osteoprogenitors (MSCs) to sites of bone formation or supply bone morphogenic signals that enhance osteoblast activity. Alternatively, VEGF may act as an autocrine/paracrine factor that acts directly on bone cells to increase their recruitment to sites of bone formation, differentiation, and activity (dotted lines)
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References

    1. Brooks M. The blood supply of bone. Buttersworths; London: 1971.
    1. Tothill P, MacPherson JN. The distribution of blood flow to the whole skeleton in dogs, rabbits and rats measured with microspheres. Clin Phys Physiol Meas. 1986;7:117–123. - PubMed
    1. Gross PM, Heistad DD, Marcus ML. Neurohumoral regulation of blood flow to bones and marrow. Am J Physiol. 1979;237:H440–448. - PubMed
    1. Gross TS, Clemens TL. Vascular control of bone remodeling. In: Zaidi M, Bittar EE, Abedanjo OA, Huang CLH, editors. Advances in organ biology. JAI; Stamford: 1998. pp. 137–160.
    1. Semenza GL. Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol. 1999;15:551–578. - PubMed

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