Linked Life Data

18056033

Source:http://linkedlifedata.com/resource/pubmed/id/18056033

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2007-12-6
pubmed:abstractText
Osteogenesis and angiogenesis are tightly coupled during bone formation and repair. Blood vessels not only carry oxygen and nutrients to the developing bone, but also play an active role in bone formation and remodeling by mediating the interaction between osteoblasts, osteocytes, osteoclasts, and vascular cells at a variety of levels. Tissue hypoxia is believed to be a major stimulus for angiogenesis by activating hypoxia-inducible factor alpha (HIFalpha) pathway, which is a central regulator of hypoxia adaptation in vertebrates. HIFalpha remains inactive under normoxic conditions through pVHL-mediated polyubiquitination and proteasomal degradation. Activation of the HIFalpha pathway by hypoxia triggers hypoxia-responsive gene expression, such as vascular endothelial growth factor (Vegf), which plays a critical role in angiogenesis, endochondral bone formation, and bone repair following fracture. Recent work from our laboratory has shown that osteoblasts use the HIFalpha pathway to sense reduced oxygen tension and transmit signals that impinge on angiogenic and osteogenic gene programs during bone formation. Using a genetic approach, we have demonstrated that overexpression of HIFalpha in mouse osteoblasts through disruption of Vhl results in profound increases in angiogenesis and osteogenesis, which appear to be mediated by cell nonautonomous mechanisms involving VEGF. These studies suggest that VEGF exerts many of its actions on bone indirectly by stimulation of angiogenesis. Whether or to what extent this angiogenic factor functions independent of endothelial cells remains to be determined.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:volume
1117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-11
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Oxygen sensing and osteogenesis.
pubmed:affiliation
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA.
pubmed:publicationType
Journal Article, Review, Research Support, N.I.H., Extramural