Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/17318
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dc.contributor.authorZannettino, A.en
dc.contributor.authorHolding, C.en
dc.contributor.authorDiamond, P.en
dc.contributor.authorAtkins, G.en
dc.contributor.authorKostakis, P.en
dc.contributor.authorFarrugia, A.en
dc.contributor.authorGamble, J.en
dc.contributor.authorTo, L.en
dc.contributor.authorFindlay, D.en
dc.contributor.authorHaynes, D.en
dc.date.issued2005en
dc.identifier.citationJournal of Cellular Physiology, 2005; 204(2):714-723en
dc.identifier.issn0021-9541en
dc.identifier.issn1097-4652en
dc.identifier.urihttp://hdl.handle.net/2440/17318-
dc.description.abstractRecent studies demonstrate roles for osteoprotegerin (OPG) in both skeletal and extra-skeletal tissues. Although its role in preventing osteoclast (OC) formation and activity is well documented, emerging evidence suggests a role of OPG in endothelial cell survival and the prevention of arterial calcification. In this communication, we show that vascular endothelial cells in situ, and human umbilical vein endothelial cells (HUVEC) in vitro, express abundant OPG. In HUVEC, OPG co-localizes with P-selectin and von Willebrand factor (vWF), within the Weibel-Palade bodies (WPB). Treatment of HUVEC with the pro-inflammatory cytokines, tumor necrosis factor (TNF)-alpha and IL-1beta, resulted in mobilization from the WPBs and subsequent secretion of OPG protein into the culture supernatant. Furthermore, TNF-alpha treatment of HUVEC resulted in a sustained increase in OPG mRNA levels and protein secretion over the 24-h treatment period. Reciprocal immunoprecipitation experiments revealed that while not associated with P-Selectin, OPG is physically complexed with vWF both within the WPB and following secretion from endothelial cells. Interestingly, this association was also identified in human peripheral blood plasma. In addition to its interaction with vWF, we show that OPG also binds with high avidity to the vWF reductase, thrombospondin (TSP-1), raising the intriguing possibility that OPG may provide a link between TSP-1 and vWF. In summary, the intracellular localization of OPG in HUVEC, in association with vWF, together with its rapid and sustained secretory response to inflammatory stimuli, strongly support a modulatory role in vascular injury, inflammation and hemostasis.en
dc.description.statementofresponsibilityA.C.W. Zannettino, C.A. Holding, P. Diamond, G.J. Atkins, P. Kostakis, A. Farrugia, J. Gamble, L.B. To, D.M. Findlay, D.R. Haynesen
dc.language.isoenen
dc.publisherWiley-Lissen
dc.source.urihttp://www3.interscience.wiley.com/cgi-bin/abstract/110433743/ABSTRACTen
dc.subjectCells, Cultured; Weibel-Palade Bodies; Endothelial Cells; Humans; Glycoproteins; Tumor Necrosis Factor-alpha; von Willebrand Factor; Carrier Proteins; Membrane Glycoproteins; Thrombospondin 1; Receptors, Tumor Necrosis Factor; Receptors, Cytoplasmic and Nuclear; Extracellular Matrix Proteins; RNA, Messenger; Tissue Distribution; Time Factors; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Osteoprotegerinen
dc.titleOsteoprotegerin (OPG) is localized to the Weibel-Palade bodies of human vascular endothelial cells and is physically associated with von Willebrand factoren
dc.typeJournal articleen
dc.identifier.rmid0020050728en
dc.identifier.doi10.1002/jcp.20354en
dc.identifier.pubid54837-
pubs.library.collectionOrthopaedics and Trauma publicationsen
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
Appears in Collections:Orthopaedics and Trauma publications

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