Characterization of interferon gamma receptors on osteoclasts: Effect of interferon gamma on osteoclastic superoxide generation

Osteoclasts are the primary cells responsible for bone resorption. Osteoclast formation and bone resorption activities involve processes tightly controlled by a network of cytokines. The presence of interferon gamma (IFN-y) receptors on osteoclasts is a necessary prerequisite for IFN-y to directly affect osteoclastic activity. To date, the presence of the IFN-y receptor on osteoclasts has not been established. This study provides evidence that osteoclasts express the IFN-γ receptor. Specific binding of IFN-γ to the osteoclastic receptor stimulates osteoclastic superoxide generation. The p91 and p47 components of the NADPH oxidase increase after IFN-y stimulation and may account for the enhanced superoxide generation. Antisense experiments targeting p91 and p47 subunits abrogate the increased osteoclastic superoxide production stimulated by IFN-γ. Thus, superoxide generation by osteoclasts is stimulated by activation of a functional IFN-y receptor on the osteoclast.