Factor VIII-von Willebrand factor complex inhibits osteoclastogenesis and controls cell survival. - Archive ouverte HAL Access content directly
Journal Articles Journal of Biological Chemistry Year : 2009

Factor VIII-von Willebrand factor complex inhibits osteoclastogenesis and controls cell survival.

(1) , (1) , (1) , (1) , (2) , (3) , (1, 4)
1
2
3
4

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.
Fichier principal
Vignette du fichier
Article_Baud_huin_et_al.pdf (382.88 Ko) Télécharger le fichier
Origin : Files produced by the author(s)
Loading...

Dates and versions

inserm-00667507 , version 1 (07-02-2012)

Identifiers

Cite

Marc Baud'Huin, Laurence Duplomb, Stéphane Téletchéa, Céline Charrier, Mike Maillasson, et al.. Factor VIII-von Willebrand factor complex inhibits osteoclastogenesis and controls cell survival.. Journal of Biological Chemistry, 2009, 284 (46), pp.31704-13. ⟨10.1074/jbc.M109.030312⟩. ⟨inserm-00667507⟩
211 View
344 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More