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-gamma) receptors on osteoclasts is a necessary prerequisite for IFN-gamma to directly affect osteoclastic activity. To date, the presence of the IFN-gamma receptor on osteoclasts has not been established. This study provides evidence that osteoclasts express the IFN-gamma receptor. Specific binding of IFN-gamma to the osteoclastic receptor stimulates osteoclastic superoxide generation. The p91 and p47 components of the NADPH oxidase increase after IFN-gamma 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-gamma. Thus, superoxide generation by osteoclasts is stimulated by activation of a functional IFN-gamma receptor on the osteoclast.
Yang
Su
S
Pediatric Endocrinology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425, USA. yangs@musc.edu
Madyastha
Prema
P
Ries
William
W
Key
Lyndon L
LL
D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D017471:Receptors, Interferon / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D019255:NADPH Oxidases; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D017471:Receptors, Interferon; D013481:Superoxides; D000096743:Interferon gamma Receptor