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Factor VIII-von Willebrand Factor Complex Inhibits Osteoclastogenesis and Control Cell Survival

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Factor VIII-von Willebrand Factor Complex Inhibits Osteoclastogenesis and Control Cell Survival, Received for publication, June 5, 2009, and in revised form, August 18, 2009 published.

Marc Baud'huin, Laurence Duplomb, Stephane Teletchea, Celine Charrier, Mike Maillasson, Marc Fouassier, and Dominique Heymann.

http://www.jbc.org/content/284/46/31704.abstract

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Abstract
Factor VIII-von Willebrand factor (FVIII?vWF) complex, a molecule involved in coagulation, can be physically associated with osteoprotegerin (OPG). OPG is an anti-osteoclastic protein and a soluble receptor for the proapoptotic protein TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), suggesting a potential role of FVIII?vWF complex in bone and cancer biology. We, thus, assessed the effects of FVIII?vWF complex on osteoclastogenesis and cell survival. We first evidenced that FVIII?vWF complex inhibited RANKL-induced osteoclastogenesis and enhanced the inhibitory effect of OPG. Interestingly, we revealed by surface plasmon resonance that FVIII?vWF complex bound to RANKL, whereas recombinant FVIII and vWF did not. By modeling, we showed that the OPG binding domain to the A1 domain of vWF was closely located and partially overlapped to its binding site to RANKL. Then, we demonstrated that FVIII?vWF complex cancelled the inhibitory activity of OPG on TRAIL-induced apoptosis and characterized interactions between these molecules. The present work evidenced a direct activity of FVIII?vWF complex on osteoclasts and on induced cell apoptosis, pointing out its potential involvement in physiological bone remodeling or in bone damages associated with severe hemophilia and cancer development.

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Solution Summary

This solution provides a summary and explanation for the journal article titled "Factor VIII-von Willebrand Factor Complex Inhibits Osteoclastogenesis and Control Cell Survival" in approximately 1000 words.

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