Expression of Nox4 in osteoclasts.
A new superoxide-generating enzyme, NADPH oxidase 4 (Nox4), contributes to osteoclastic superoxide production. In this study, we demonstrated that Nox4 is expressed at a higher level in osteoclasts than that in precursor cells. This result suggested that Nox4 is upregulated during the differentiation and development of osteoclasts. Cotransfection of Nox4/P22 DNA resulted in enhanced superoxide production in osteoclasts, indicating that P22 may be a necessary factor for the Nox4 activity. In addition, expression of both cathepsin K and TRAP is increased significantly in osteoclasts cotransfected with Nox4/P22. Further study revealed that JNK was activated and that NF-kappa B was inhibited in Nox4/P22 cotransfected osteoclasts. These findings suggest that superoxide and/or superoxide derived molecules may modulate the signal transduction pathways necessary for osteoclasts to function.
Yang
Su
S
Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425,USA. yangs@musc.edu
Zhang
Yizhong
Y
Ries
William
W
Key
Lyndon
L
D000818:Animals; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D048670:MAP Kinase Kinase 4; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D014162:Transfection
D016328:NF-kappa B; D012333:RNA, Messenger; D013481:Superoxides; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D016186:Receptor, Macrophage Colony-Stimulating Factor; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D002403:Cathepsins; D056657:Cathepsin K; C534132:Ctsk protein, mouse