THE ESCHERICHIA-COLI CHAPERONIN-60 (GROEL) IS A POTENT STIMULATOR OF OSTEOCLAST FORMATION

Chaperonins (cpns) are intracellular oligomeric protein complexes that fold and refold proteins In a catalytic manner and aid in the transme mbrane transport of cellular proteins. We reported previously that the lipopolysaccharide-free recombinant cpn60 of Escherichia coli (groEL) is able to stimulate the breakdown of murine calvarial bone in cultur e and showed that such resorption is potently inhibited by an inhibito r of the enzyme cyclo-oxygenase and to a lesser extent by inhibitors o f 5-lipoxygenase. In this study, we have investigated the effects of g roEL on the resorptive activity and formation of osteoclasts in cultur e. In low density, osteoclast-containing cultures from neonatal rats i ncubated for 24 or 96 h on dentine discs, groEL (1-1000 ng/ml) stimula ted resorption pit formation up to 4-fold, but this effect,vas essenti ally dependent on cell number, Using 12-day cultures of mouse bone mar row to assess osteoclast recruitment, groEL (1-1000 ng/ml) caused a dr amatic dose-dependent stimulation of the formation of tartrate-resista nt acid phosphatase-positive multinucleated cells and the resorption o f the dentine on which bone marrow cells were cultured. Osteoclast for mation elicited by groEL was almost completely abolished by indomethac in, an inhibitor of cyclo-oxygenase, but was unaffected by inhibitors of 5-lipoxygenase, suggesting that prostaglandins but not leukotrienes may mediate the action of groEL on osteoclastogenesis. It is possible that bacterial cpn60s such as groEL may play a role in the osteolysis associated with bone infections. Whether endogenous (''self'') chaper onins have a role in other bone loss disorders, such as osteoporosis, is an intriguing possibility.