Prostaglandin E2 inhibits formation of osteoclastlike cells in long-term human marrow cultures but is not a mediator of the inhibitory effects of transforming growth factor beta.

Prostaglandins are important local regulators of bone cell function and have been shown to have multiple effects on osteoclasts. Using a human bone marrow culture system in which multinucleated cells with osteoclast characteristics form, we have recently shown that TGF-beta is a potent inhibitor of osteoclastlike cell formation and appears to act at several stages of their development. Because it has been suggested that the effects of TGF-beta are mediated via a prostaglandin-dependent mechanism, we determined the effects of prostaglandin E2 (PGE2) on total and osteoclastlike cell formation (detected by reactivity with the 23c6 monoclonal antibody, which identifies osteoclasts) in human marrow cultures and tested whether prostaglandin synthesis was responsible for the inhibitory effects of TGF-beta on multinucleated cell formation. These studies show that PGE2 is a potent inhibitor of both 23c6-positive and negative multinucleate cell formation in human marrow cultures and that the effects of TGF-beta on multinucleated cell formation are not mediated by PGE2.