The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development.

The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. Research Abstract Details 

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The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. Abstract Text:

Skeletal development and turnover occur in close spatial and temporal association with angiogenesis. Osteoblasts are ideally situated in bone to sense oxygen tension and respond to hypoxia by activating the hypoxia-inducible factor alpha (HIF alpha) pathway. Here we provide evidence that HIF alpha promotes angiogenesis and osteogenesis by elevating VEGF levels in osteoblasts. Mice overexpressing HIF alpha in osteoblasts through selective deletion of the von Hippel-Lindau gene (Vhl) expressed high levels of Vegf and developed extremely dense, heavily vascularized long bones. By contrast, mice lacking Hif1a in osteoblasts had the reverse skeletal phenotype of that of the Vhl mutants: long bones were significantly thinner and less vascularized than those of controls. Loss of Vhl in osteoblasts increased endothelial sprouting from the embryonic metatarsals in vitro but had little effect on osteoblast function in the absence of blood vessels. Mice lacking both Vhl and Hif1a had a bone phenotype intermediate between those of the single mutants, suggesting overlapping functions of HIFs in bone. These studies suggest that activation of the HIF alpha pathway in developing bone increases bone modeling events through cell-nonautonomous mechanisms to coordinate the timing, direction, and degree of new blood vessel formation in bone.

The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. Publishing Authors By Initials

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The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of clinical investigation

VOLUME: 117

Page Numbers: 1616-26

Journal Abbreviation: J. Clin. Invest.

ISSN: 0021-9738

DAY: 3

MONTH: Jun

YEAR: 2007

The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7802877

The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. Keywords Mesh Terms:

KEYWORDS: Von Hippel-Lindau Tumor Suppressor Prote

MESH TERMS: genetics

Chemical & Substance for Abstract: The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. Information

Substance Name: Von Hippel-Lindau Tumor Suppressor Prote

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development.

AFFILIATION: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA.

Country: United States

AGENCY: United States NIAMS

GRANT: R01 AR049410

ACRONYM: AR

MEDLINETA: J Clin Invest

REFSOURCE: J Clin Invest. 2007 Jun;117(6):1477-80

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