Expression of Nox4 in osteoclasts

J Cell Biochem. 2004 May 15;92(2):238-48. doi: 10.1002/jcb.20048.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cathepsin K
  • Cathepsins / genetics
  • Cathepsins / metabolism
  • Cells, Cultured
  • Gene Expression Regulation
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Kinase 4
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • NADPH Oxidase 4
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism*
  • NF-kappa B / metabolism
  • Osteoclasts / cytology*
  • Osteoclasts / metabolism*
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Macrophage Colony-Stimulating Factor / genetics
  • Signal Transduction
  • Superoxides / metabolism
  • Transfection


  • NF-kappa B
  • RNA, Messenger
  • Superoxides
  • NADPH Oxidase 4
  • NADPH Oxidases
  • Nox4 protein, mouse
  • Receptor, Macrophage Colony-Stimulating Factor
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases
  • Cathepsins
  • Cathepsin K
  • Ctsk protein, mouse