Chonnam Med J.  2016 Jan;52(1):12-17. 10.4068/cmj.2016.52.1.12.

Signaling Pathways in Osteoclast Differentiation

Affiliations
  • 1Department of Pharmacology, Chonnam National University Medical School, Gwangju, Korea. nacksung@jnu.ac.kr

Abstract

Osteoclasts are multinucleated cells of hematopoietic origin that are responsible for the degradation of old bone matrix. Osteoclast differentiation and activity are controlled by two essential cytokines, macrophage colony-stimulating factor (M-CSF) and the receptor activator of nuclear factor-kappaB ligand (RANKL). M-CSF and RANKL bind to their respective receptors c-Fms and RANK to stimulate osteoclast differentiation through regulation of delicate signaling systems. Here, we summarize the critical or essential signaling pathways for osteoclast differentiation including M-CSF-c-Fms signaling, RANKL-RANK signaling, and costimulatory signaling for RANK.

Keyword

Bone and bones; Macrophage colony-stimulating factor; RANK ligand; Osteoclasts; Signal transduction

MeSH Terms

Bone and Bones
Bone Matrix
Cytokines
Macrophage Colony-Stimulating Factor
Osteoclasts*
RANK Ligand
Signal Transduction
Cytokines
Macrophage Colony-Stimulating Factor
RANK Ligand

Figure

  • FIG. 1 Osteoclast differentiation is stimulated by M-CSF and RANKL. M-CSF induces the proliferation and survival of osteoclast precursor cells through activation of ERK and Akt. RANKL recruits TRAF6 to activate MAPKs, Akt, and NFATc1 to promote differentiation of osteoclast precursors to osteoclasts. In addition to RANKL signaling, costimulatory signaling provides robust NFATc1 induction through activation of calcium signaling.


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