Osteoclastic superoxide production and bone resorption: stimulation and inhibition by modulators of NADPH oxidase

• Published in: Journal of bone and mineral research Vol. 11; no. 5; p. 671
• Main Authors: Darden, A G, Ries, W L, Wolf, W C, Rodriguiz, R M, Key, Jr, L L
• Format: Journal Article
• Language: English
• Published: United States 01.05.1996
• Subjects: Animals; Biphenyl Compounds - pharmacology; Bone Resorption; Interferon-gamma - pharmacology; Mice; Mice, Inbred C57BL; NADPH Oxidases - antagonists & inhibitors; NADPH Oxidases - metabolism; Onium Compounds - pharmacology; Osteoclasts - enzymology; Osteoclasts - pathology; Skull - enzymology; Skull - pathology; Superoxides - metabolism
• ISSN: 0884-0431
• DOI: 10.1002/jbmr.5650110515

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