Linked Life Data

19277991

Source:http://linkedlifedata.com/resource/pubmed/id/19277991

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-4-27
pubmed:abstractText
Changes in regional oxygen tension that occur during skeletal development and fracture stimulate local bone cell activity to regulate bone formation, maintenance, and repair. The adaptive responses of bone cells to hypoxia are only beginning to be understood. The transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) is activated under hypoxia and promotes expression of genes required for adaptation and cell survival, and also regulates both bone development and fracture repair. We have previously demonstrated that hypoxic osteoblasts increase PGE(2) release and expression of the PGE(2) receptor EP1. In the present studies, we investigated the impact of altered HIF-1alpha activity and expression on EP1 expression in osteoblasts. HIF-1alpha stabilization was induced in cells cultured in 21% oxygen by treatment with dimethyloxaloglycine (DMOG) or siRNA targeted against PHD2. To implicate HIF-1alpha in hypoxia-induced EP1 expression, osteoblastic cells were treated with siRNA targeted against HIF-1alpha prior to exposure to hypoxia. EP1 expression was significantly increased in cells cultured in 21% oxygen with DMOG or PHD2 siRNA treatment compared to controls. Hypoxia responsive element (HRE) activation in hypoxia was attenuated in cells treated with HIF-1alpha siRNA compared to controls, indicating HIF-1alpha as the functional HIF-alpha isoform in this system. Furthermore, hypoxic cells treated with HIF-1alpha siRNA demonstrated reduced EP1 expression in hypoxia compared to controls. Inhibition of SAPK/JNK activity significantly reduced hypoxia-induced EP1 expression but had no impact on HIF-1alpha expression or activity. These data strongly implicate a role for HIF-1alpha in hypoxia-induced EP1 expression and may provide important insight into the mechanisms by which HIF-1alpha regulates bone development and fracture repair.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1097-4644
pubmed:author
pubmed:copyrightInfo
2009 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
107
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
233-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19277991-Animals, pubmed-meshheading:19277991-Blotting, Western, pubmed-meshheading:19277991-Cell Hypoxia, pubmed-meshheading:19277991-Cell Line, pubmed-meshheading:19277991-Gene Expression Regulation, pubmed-meshheading:19277991-Gene Silencing, pubmed-meshheading:19277991-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:19277991-MAP Kinase Kinase 4, pubmed-meshheading:19277991-Mice, pubmed-meshheading:19277991-Osteoblasts, pubmed-meshheading:19277991-Procollagen-Proline Dioxygenase, pubmed-meshheading:19277991-RNA, Small Interfering, pubmed-meshheading:19277991-Receptors, Prostaglandin E, pubmed-meshheading:19277991-Receptors, Prostaglandin E, EP1 Subtype, pubmed-meshheading:19277991-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19277991-Signal Transduction, pubmed-meshheading:19277991-Transfection
pubmed:year
2009
pubmed:articleTitle
HIF-1alpha regulates hypoxia-induced EP1 expression in osteoblastic cells.
pubmed:affiliation
Department of Surgical and Radiological Sciences, University of California at Davis, 95616, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural