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Review
. 2016 Jan;52(1):12-7.
doi: 10.4068/cmj.2016.52.1.12. Epub 2016 Jan 19.

Signaling Pathways in Osteoclast Differentiation

Jung Ha Kim  1 , Nacksung Kim  1
Affiliations
Review

Signaling Pathways in Osteoclast Differentiation

Jung Ha Kim et al. Chonnam Med J. 2016 Jan.

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-κB 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.

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

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Conflict of interest statement

CONFLICT OF INTEREST STATEMENT: None declared.

Figures

FIG. 1
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.
See this image and copyright information in PMC

References

    1. Takayanagi H. Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol. 2007;7:292–304. - PubMed
    1. Seeman E, Delmas PD. Bone quality--the material and structural basis of bone strength and fragility. N Engl J Med. 2006;354:2250–2261. - PubMed
    1. Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev Genet. 2003;4:638–649. - PubMed
    1. Sherr CJ. Colony-stimulating factor-1 receptor. Blood. 1990;75:1–12. - PubMed
    1. Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev. 1999;20:345–357. - PubMed