OSTEOPROTEGERIN IS A RECEPTOR FOR THE CYTOTOXIC LIGAND TRAIL

TRAIL is a tumor necrosis factor-related ligand that induces apoptosis upon binding to its death domain-containing receptors, DR4 and DR5. T wo additional TRAIL receptors, TRID/DcR1 and DcR2, lack functional dea th domains and function as decoy receptors for TRAIL. We have identifi ed a fifth TRAIL receptor, namely osteoprotegerin (OPG), a secreted tu mor necrosis factor receptor homologue that inhibits osteoclastogenesi s and increases bone density in vivo. OPG-Fc binds TRAIL with an affin ity of 3.0 nM, which is slightly weaker than the interaction of TRID-F c or DR5-Fc with TRAIL. OPG inhibits TRAIL-induced apoptosis of Jurkat cells, Conversely, TRAIL blocks the anti-osteoclastogenic activity of OPG, These data suggest potential cross-regulatory mechanisms by OPG and TRAIL.