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Osteoprotegerin decreases human osteoclast apoptosis by inhibiting the TRAIL pathway
Author(s) -
Chamoux Estelle,
Houde Nicolas,
L'Eriger Karine,
Roux Sophie
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21430
Subject(s) - osteoprotegerin , osteoclast , apoptosis , microbiology and biotechnology , chemistry , medicine , biology , receptor , biochemistry , activator (genetics)
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.