IL-23 promotes osteoclast formation by up-regulation of receptor activator of NF-kappaB (RANK) expression in myeloid precursor cells

Eur J Immunol. 2008 Oct;38(10):2845-54. doi: 10.1002/eji.200838192.


Inflammation-mediated bone loss is a major feature of various bone diseases including rheumatoid arthritis, osteoarthritis and advanced periodontitis. Enhanced osteoclast development or activity at the inflammation site results in bone resorption. IL-23 is a heterodimeric cytokine belonging to the IL-6/IL-12 family that has been implicated in the pathogenesis of rheumatoid arthritis and demonstrated to play a role in osteoclastogenesis via stimulation of IL-17 production. In this study we investigated whether IL-23 contributes to the regulation of osteoclast differentiation independent of the IL-17 pathway. We show that IL-23 dose-dependently up-regulates receptor activator of NF-kappaB expression in primary murine bone marrow macrophages and RAW264.7 cells and thereby promotes commitment of myeloid precursor cells to receptor activator of NF-kappaB ligand-mediated osteoclastic differentiation. However, IL-23 by itself is insufficient to induce osteoclastogenesis. Increased osteoclastic differentiation of cells was associated with enhanced cathepsin K expression and dentine resorption indicating enhanced formation of functional osteoclasts. IL-17 was not detectable in culture supernatants and when added to cultures, did not promote differentiation of RAW264.7 cells. These results demonstrate that IL-23 can act directly on myeloid precursor cells in addition to indirectly stimulating receptor activator of NF-kappaB ligand production in osteoblasts and explains its potency in driving osteoclast development in inflammation-mediated bone pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Interleukin-17 / metabolism*
  • Interleukin-23 / metabolism*
  • Interleukins / metabolism*
  • Male
  • Mice
  • Mice, Inbred DBA
  • Myeloid Progenitor Cells / metabolism*
  • Osteoclasts / cytology
  • Osteoclasts / physiology*
  • RANK Ligand / metabolism
  • Receptor Activator of Nuclear Factor-kappa B / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Up-Regulation


  • Il27 protein, mouse
  • Interleukin-17
  • Interleukin-23
  • Interleukins
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Recombinant Fusion Proteins
  • Tnfrsf11a protein, mouse