Current Understanding of RANK Signaling in Osteoclast Differentiation and Maturation
- 주제(키워드) nuclear factor-kappa B , nuclear factor of activated Tcells cytoplasmic 1 , osteoclasts , receptor activator of nuclear factor-kappa B , tumor necrosis factor receptor-associated factors
- 주제(기타) Biochemistry & Molecular Biology; Cell Biology
- 발행기관 KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
- 발행년도 2017
- URI http://www.dcollection.net/handler/ewha/000000149535
- 본문언어 영어
- Published As http://dx.doi.org/10.14348/molcells.2017.0225
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Osteoclasts are bone-resorbing cells that are derived from hematopoietic precursor cells and require macrophage-colony stimulating factor and receptor activator of nuclear factor-kappa B ligand (RANKL) for their survival, proliferation, differentiation, and activation. The binding of RANKL to its receptor RANK triggers osteoclast precursors to differentiate into osteoclasts. This process depends on RANKL-RANK signaling, which is temporally regulated by various adaptor proteins and kinases. Here we summarize the current understanding of the mechanisms that regulate RANK signaling during osteoclastogenesis. In the early stage, RANK signaling is mediated by recruiting adaptor molecules such as tumor necrosis factor receptor-associated factor 6 (TRAF6), which leads to the activation of mitogen-activated protein kinases (MAPKs), and the transcription factors nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1). Activated NF-kappa B induces the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), which is the key osteoclastogenesis regulator. In the intermediate stage of signaling, the co-stimulatory signal induces Ca2+ oscillation via activated phospholipase C gamma 2 (PLC gamma 2) together with c-Fos/AP1, wherein Ca2+ signaling facilitates the robust production of NFATc1. In the late stage of osteoclastogenesis, NFATc1 translocates into the nucleus where it induces numerous osteoclast-specific target genes that are responsible for cell fusion and function.
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