OSTEOCLASTIC SUPEROXIDE PRODUCTION AND BONE-RESORPTION - STIMULATION AND INHIBITION BY MODULATORS OF NADPH OXIDASE

Production of superoxide radicals by osteoclasts is necessary for norm al bone degradation, White blood cell superoxide, needed for bacterial killing, is produced by activated NADPH oxidase, Since osteoclasts an d white blood cells share a common hematopoietic origin, we initiated experiments to test the hypothesis that superoxide radicals at the ost eoclast-bone interface are produced by NADPH oxidase. Diphenyl iodoniu m (IDP), an inhibitor of NADPH oxidase, blocked superoxide generation and decreased osteoclastic bone resorption in cultures of calvarial ex plants from normal mice. Interferon (IFN) gamma, a stimulant of NADPH oxidase activity, increased superoxide production and bone resorption in cultures of calvarial explants hom osteopetrotic (microphthalmic) m ice, IDP blocked the stimulatory effects of IFN in this bone resorptio n model, These data suggest that osteoclastic superoxide is produced b y NADPH oxidase.