Current Understanding of RANK Signaling in Osteoclast Differentiation and Maturation.

Content Provider	Europe PMC
Author	Park, Jin Hee Lee, Na Kyung Lee, Soo Young
Copyright Year	2017
Abstract	Osteoclasts are bone-resorbing cells that are derived from hematopoietic precursor cells and require macrophage-colony stimulating factor and receptor activator of nuclear factor-κB 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-κB (NF-κB) and activator protein-1 (AP-1). Activated NF-κB 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 Cγ2 (PLCγ2) together with c-Fos/AP-1, 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.
ISSN	10168478
Journal	Molecules and Cells
Volume Number	40
PubMed Central reference number	PMC5682248
Issue Number	10
PubMed reference number	29047262
e-ISSN	02191032
DOI	10.14348/molcells.2017.0225
Language	English
Publisher	Korean Society for Molecular and Cellular Biology
Publisher Date	2017-10-17
Access Restriction	Open
Rights License	This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/. © The Korean Society for Molecular and Cellular Biology. All rights reserved.
Subject Keyword	nuclear factor-κB nuclear factor of activated T-cells cytoplasmic 1 osteoclasts receptor activator of nuclear factor-κB tumor necrosis factor receptor-associated factors
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Molecular Biology