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https://hdl.handle.net/2440/17318
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Type: | Journal article |
Title: | Osteoprotegerin (OPG) is localized to the Weibel-Palade bodies of human vascular endothelial cells and is physically associated with von Willebrand factor |
Author: | Zannettino, A. Holding, C. Diamond, P. Atkins, G. Kostakis, P. Farrugia, A. Gamble, J. To, L. Findlay, D. Haynes, D. |
Citation: | Journal of Cellular Physiology, 2005; 204(2):714-723 |
Publisher: | Wiley-Liss |
Issue Date: | 2005 |
ISSN: | 0021-9541 1097-4652 |
Statement of Responsibility: | A.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. Haynes |
Abstract: | Recent 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. |
Keywords: | Cells, 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 Osteoprotegerin |
DOI: | 10.1002/jcp.20354 |
Published version: | http://www3.interscience.wiley.com/cgi-bin/abstract/110433743/ABSTRACT |
Appears in Collections: | Aurora harvest 6 Orthopaedics and Trauma publications |
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