Tumor necrosis factor alpha-induced osteoclastogenesis requires tumor necrosis factor receptor-associated factor 6

J Bone Miner Res. 2001 Sep;16(9):1593-9. doi: 10.1359/jbmr.2001.16.9.1593.


Although tumor necrosis factor receptor-associated factor 6 (TRAF6) is required in receptor activator of NF-kappaB-receptor activator of NF-kappaB ligand (RANK-RANKL) signaling for osteoclastogenesis, it has remained unclear whether TRAF6 is crucial in tumor necrosis factor alpha (TNF-alpha)-induced osteoclastogenesis. We examined TRAF6 function in the TNF-alpha-induced osteoclastogenesis by using osteoclast progenitor cells from TRAF6-deficient mice. The results indicated that TNF-alpha did not effectively induce osteoclast differentiation from osteoclast progenitor cells derived from these mice into mature multinucleated osteoclasts, although c-jun N-terminal kinase (JNK) and TNF-alpha activation was observed in osteoclast progenitor cells. Thus, we have provided the first evidence showing that TRAF6 is involved in TNF-alpha-induced osteoclastogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteogenesis / physiology*
  • Proteins / genetics
  • Proteins / metabolism*
  • Proteins / physiology
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Signal Transduction*
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • TNF Receptor-Associated Factor 6
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation


  • NF-kappa B
  • Proteins
  • Receptors, Tumor Necrosis Factor
  • TNF Receptor-Associated Factor 6
  • Tumor Necrosis Factor-alpha
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases