Cytokine-mediated immunomodulation of osteoclastogenesis

Bone. 2022 Nov;164:116540. doi: 10.1016/j.bone.2022.116540. Epub 2022 Aug 27.


Cytokines are an important set of proteins regulating bone homeostasis. In inflammation induced bone resorption, cytokines, such as RANKL, TNF-α, M-CSF, are indispensable for the differentiation and activation of resorption-driving osteoclasts, the process we know as osteoclastogenesis. On the other hand, immune system produces a number of regulatory cytokines, including IL-4, IL-10 and IFNs, and limits excessive activation of osteoclastogenesis and bone loss during inflammation. These unique properties make cytokines powerful targets as rheostat to maintain bone homeostasis and for potential immunotherapies of inflammatory bone diseases. In this review, we summarize recent advances in cytokine-mediated regulation of osteoclastogenesis and provide insights of potential translational impact of bench-side research into clinical treatment of bone disease.

Keywords: Bone loss; Cytokines; Immunomodulation; Osteoclastogenesis.

Publication types

  • Review

MeSH terms

  • Bone Resorption* / metabolism
  • Cell Differentiation
  • Cytokines / metabolism
  • Humans
  • Immunomodulation
  • Inflammation / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-4 / metabolism
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Osteoclasts / metabolism
  • Osteogenesis*
  • RANK Ligand / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • RANK Ligand
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Macrophage Colony-Stimulating Factor