The role of cytokines in inflammatory bone loss

Immunol Invest. 2013;42(7):555-622. doi: 10.3109/08820139.2013.822766.


Chronic inflammatory processes close to bone often lead to loss of bone in diseases such as rheumatoid arthritis, periodontitis, loosened joint prosthesis and tooth implants. This is mainly due to local formation of bone resorbing osteoclasts which degrade bone without any subsequent coupling to new bone formation. Crucial for osteoclastogenesis is stimulation of mononuclear osteoclast progenitors by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) which induces their differentiation along the osteoclastic lineage and the fusion to mature, multinucleated osteoclasts. M-CSF and RANKL are produced by osteoblasts/osteocytes and by synovial and periodontal fibroblasts and the expression is regulated by pro- and anti-inflammatory cytokines. These cytokines also regulate osteoclastic differentiation by direct effects on the progenitor cells. In the present overview, we introduce the basic concepts of osteoclast progenitor cell differentiation and summarize the current knowledge on cytokines stimulating and inhibiting osteoclastogenesis by direct and indirect mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Resorption / drug therapy
  • Bone Resorption / immunology*
  • Bone Resorption / metabolism*
  • Cell Differentiation
  • Cytokines / metabolism*
  • Humans
  • Inflammation / immunology*
  • Inflammation / metabolism*
  • Inflammation Mediators / metabolism
  • Macrophage Colony-Stimulating Factor / metabolism
  • Macrophage Colony-Stimulating Factor / pharmacology
  • NF-kappa B / metabolism
  • NFATC Transcription Factors / metabolism
  • Osteoclasts / cytology
  • Osteoclasts / immunology
  • Osteoclasts / metabolism
  • RANK Ligand / metabolism
  • Receptors, Immunologic / metabolism
  • Transcription Factor AP-1 / metabolism


  • Cytokines
  • Inflammation Mediators
  • NF-kappa B
  • NFATC Transcription Factors
  • RANK Ligand
  • Receptors, Immunologic
  • Transcription Factor AP-1
  • Macrophage Colony-Stimulating Factor