Document Detail


Novel extraneural role of Nogo-A: Modulation of osteoclastogenesis via positive feedback regulation of NFATc1.
MedLine Citation:
PMID:  22392845     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Osteoclasts are bone-resorbing cells differentiated from macrophage/monocyte lineage precursors upon receptor activator of NFkB ligand (RANKL) stimulation. In a proteomic approach to identify proteins involved in osteoclastogenesis, we observed a dramatic increase in the expression of Nogo-A upon RANKL stimulation of mouse bone marrow macrophages (BMMs) in a nuclear factor of activated T cell cytoplasmic 1 (NFATc1)-dependent manner. The knock-down of Nogo-A in BMMs significantly reduced RANKL-dependent osteoclast differentiation accompanied by diminished NFATc1 induction, suggesting that a positive feedback mechanism is involved. Conversely, Nogo-A overexpression in BMMs as well as in RAW264.7 macrophages greatly augmented osteoclastogenesis with concomitant increase in the NFATc1 induction. Both mitogen activated protein kinase pathway and calcium oscillation, which are central to the RANKL-dependent NFATc1 activation and induction, were enhanced by Nogo-A. Finally, Nogo-A knock-down in mouse calvariae prevented IL-1-induced bone loss. These findings not only reveal unprecedented extraneural role of Nogo-A in osteoclastogenesis but also suggest a novel drug target against bone-lytic diseases. © 2012 American Society for Bone and Mineral Research.
Authors:
Youngkyun Lee; Hyung Joon Kim; Cheol Kyu Park; Woo-Shin Kim; Zang Hee Lee; Hong-Hee Kim
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-27
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  -     ISSN:  1523-4681     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-3-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 American Society for Bone and Mineral Research.
Affiliation:
1Department of Cell and Developmental Biology, School of Dentistry, Seoul National University, Seoul 110-749, Korea; Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
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