Document Detail


Regulatory mechanism of osteoclastogenesis by RANKL and Wnt signals.
MedLine Citation:
PMID:  21196156     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Osteoclasts develop from monocyte-macrophage lineage cells under the regulation of osteoblasts. Osteoblasts express two cytokines essential for osteoclastogenesis, macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-KappaB ligand (RANKL). Osteoblasts also produce osteoprotegerin (OPG), a decoy receptor for RANKL, which inhibits the interaction between RANKL and RANK, a receptor of RANKL. Bone resorption-stimulating factors act on osteoblasts to regulate RANKL and OPG expression. Nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) is a master transcription factor for osteoclast differentiation. The immunoreceptor tyrosine-based activation motif (ITAM)-mediated signal was discovered as a co-stimulatory signal in RANKL-induced osteoclastogenesis. Wnt proteins activate two pathways: beta-catenin-dependent canonical and beta-catenin-independent noncanonical pathways. Wnt proteins promote differentiation of osteoblasts through the canonical pathway. The canonical pathway in osteoblasts also suppresses osteoclastogenesis through up-regulation of OPG expression and down-regulation of RANKL expression. In contrast, activation of the noncanonical pathway in osteoclast precursors enhances RANKL-induced osteoclastic differentiation. Thus, Wnt signals in osteoblasts and osteoclast precursors play important roles in osteoclastogenesis. This review summarizes the regulatory mechanism of osteoclastogenesis by RANKL and Wnt signals.
Authors:
Naoyuki Takahashi; Kazuhiro Maeda; Akihiro Ishihara; Shunsuke Uehara; Yasuhiro Kobayashi
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Publication Detail:
Type:  Journal Article; Review     Date:  2011-01-01
Journal Detail:
Title:  Frontiers in bioscience (Landmark edition)     Volume:  16     ISSN:  1093-4715     ISO Abbreviation:  Front Biosci (Landmark Ed)     Publication Date:  2011  
Date Detail:
Created Date:  2011-01-03     Completed Date:  2011-04-21     Revised Date:  2013-07-29    
Medline Journal Info:
Nlm Unique ID:  101612996     Medline TA:  Front Biosci (Landmark Ed)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  21-30     Citation Subset:  IM    
Affiliation:
Institute for Oral Science, Matsumoto Dental University, 1780 Gobara, Hiro-oka, Shiojiri, Nagano 399-0781, Japan. takahashinao@po.mdu.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing
Animals
Bone Resorption / physiopathology
Cell Differentiation
Humans
Macrophage Colony-Stimulating Factor / metabolism
Membrane Proteins / physiology
NFATC Transcription Factors / physiology
Osteoclasts / cytology,  physiology*
RANK Ligand / physiology*
Signal Transduction
Wnt Proteins / physiology*
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/DCSTAMP protein, human; 0/Membrane Proteins; 0/NFATC Transcription Factors; 0/RANK Ligand; 0/Wnt Proteins; 81627-83-0/Macrophage Colony-Stimulating Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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