TRAF5 functions in both RANKL- and TNFalpha-induced osteoclastogenesis

J Bone Miner Res. 2003 Mar;18(3):443-50. doi: 10.1359/jbmr.2003.18.3.443.


Although TRAF6 is essential for both RANKL- and TNFalpha-induced osteoclastogenesis, it has remained unclear whether other members of the TRAF family are involved in osteoclastogenesis. We examined TRAF5 function in both RANKL- and TNFalpha-induced osteoclastogenesis by using osteoclast progenitor cells from TRAF5-deficient mice. The results demonstrated that RANKL or TNFalpha 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 NF-kappaB activation was apparently observed in osteoclast progenitor cells. In the parathyroid hormone (PTH)-induced hypercalcemia model, calcium concentration peaked at day 3 after administration. However, in TRAF5-deficient mice, this peak was delayed and found at day 5, showing less effective osteoclast differentiation. Thus, we have provided the first evidence showing that TRAF5 is involved in osteoclastogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / physiology*
  • Cell Differentiation
  • Cell Line
  • JNK Mitogen-Activated Protein Kinases
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Osteoclasts / cytology*
  • Proteins / genetics
  • Proteins / physiology*
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Signal Transduction / physiology
  • TNF Receptor-Associated Factor 5
  • Tumor Necrosis Factor-alpha / physiology*


  • Carrier Proteins
  • Membrane Glycoproteins
  • NF-kappa B
  • Proteins
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • TNF Receptor-Associated Factor 5
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse
  • Tumor Necrosis Factor-alpha
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases