Osteoprotegerin is produced when prostaglandin synthesis is inhibited causing osteoclasts to detach from the surface of mouse parietal bone and attach to the endocranial membrane

Osteoclast differentiation and activation is controlled, at least in part, by the counterbalancing influences of osteoprotegerin Ligand (OPGL) and ost eoprotegerin (OPG), Nonsteroidal anti-inflammatory drugs have been shown to inhibit bone loss in vivo and bone resorption in vitro, and this is associ ated with a loss of osteoclasts from the bone surface. We test the hypothes is that OPG mediates the inhibition of osteoclast activity that occurs with indomethacin in the mouse calvaria, Recombinant human OPG, like indomethac in, was found to cause osteoclasts to detach from the bone surface and atta ch to the adjacent endocranial membrane (periosteum). Recombinant human OPG also inhibited the stimulatory effect of prostaglandin E-2 (PGE(2)), parat hyroid hormone (PTH), and 1,25-dihydroxyvitamin D-3 (1,25D(3)) on osteoclas t adhesion to hone after an incubation with indomethacin, A function-blocki ng antibody to OPG and soluble human OPGL both inhibited the effect of indo methacin, leaving active osteoclasts on the bone. OPG activity was detected in the culture medium from indomethacin-treated bones and PTH, PGE(2), 1,2 5D(3), and dexamethasone all inhibited the production of OPG activity. We c onclude that, in the absence of specific stimulators of bone resorption, OP G is produced by the mouse calvaria in vitro, which inhibits bone resorptio n by causing osteoclasts to detach from the bone surface. (Bone 28:208-214; 2001) (C) 2001 by Elsevier Science Inc. All rights reserved.