Osteoprotegerin decreases human osteoclast apoptosis by inhibiting the TRAIL pathway
Article first published online: 12 MAR 2008
Copyright © 2008 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 216, Issue 2, pages 536–542, August 2008
How to Cite
Chamoux, E., Houde, N., L'Eriger, K. and Roux, S. (2008), Osteoprotegerin decreases human osteoclast apoptosis by inhibiting the TRAIL pathway. J. Cell. Physiol., 216: 536–542. doi: 10.1002/jcp.21430
- Issue published online: 23 MAY 2008
- Article first published online: 12 MAR 2008
- Manuscript Accepted: 30 JAN 2008
- Manuscript Received: 2 OCT 2007
- FRSQ (Fonds de la Recherche en Santé du Québec)
- The Arthritis Society
Osteoprotegerin (OPG) is a secreted decoy receptor that recognizes RANKL, and blocks the interaction between RANK and RANKL, leading to the inhibition of osteoclast differentiation and activation. As OPG is a major inhibitor of bone resorption, we wondered whether OPG could modulate osteoclast survival/apoptosis. Osteoclast apoptosis was evaluated by adding various doses of OPG to human osteoclast cultures obtained from cord blood monocytes. Surprisingly, apoptosis decreased after adding the OPG. We hypothesized that OPG may block its second ligand, TRAIL, which is involved in osteoclast apoptosis. We showed that osteoclasts expressed TRAIL, and that TRAIL levels in the culture medium dose-dependently decreased in presence of OPG, as did the level of activated caspase-8 in osteoclasts. In addition, the expression of TRAIL by osteoclasts was not affected in the presence of OPG. Our findings suggest that OPG inhibits osteoclast apoptosis, at least in part, by binding and thus inhibiting endogenously produced TRAIL in human osteoclast cultures. TRAIL could be an autocrine factor for the regulation of osteoclast survival/apoptosis. J. Cell. Physiol. 216: 536–542, 2008. © 2008 Wiley-Liss, Inc.