Abstract
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.
Copyright 2004 Wiley-Liss, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cathepsin K
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Cathepsins / genetics
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Cathepsins / metabolism
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Cells, Cultured
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Gene Expression Regulation
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JNK Mitogen-Activated Protein Kinases / metabolism
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MAP Kinase Kinase 4
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Mice
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Mitogen-Activated Protein Kinase Kinases / metabolism
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NADPH Oxidase 4
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NADPH Oxidases / genetics
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NADPH Oxidases / metabolism*
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NF-kappa B / metabolism
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Osteoclasts / cytology*
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Osteoclasts / metabolism*
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Protein Binding
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptor, Macrophage Colony-Stimulating Factor / genetics
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Signal Transduction
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Superoxides / metabolism
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Transfection
Substances
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NF-kappa B
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RNA, Messenger
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Superoxides
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NADPH Oxidase 4
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NADPH Oxidases
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Nox4 protein, mouse
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Receptor, Macrophage Colony-Stimulating Factor
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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Mitogen-Activated Protein Kinase Kinases
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Cathepsins
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Cathepsin K
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Ctsk protein, mouse