Document Detail


Roles of cathelicidin-related antimicrobial peptide in murine osteoclastogenesis.
MedLine Citation:
PMID:  23826736     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cathelicidin-related antimicrobial peptide (CRAMP) not only kills bacteria but also binds to lipopolysaccharide (LPS) to neutralize its activity. CRAMP is highly expressed in bone marrow and its expression is reported to be up-regulated by inflammatory and infectious stimuli. Here, we examined the role of CRAMP in murine osteoclastogenesis. Osteoclasts were formed in co-cultures of osteoblasts and bone marrow cells in response to 1α,25-dihydroxyvitamin D3 [1α,25(OH)2 D3 ], prostaglandin E2 (PGE2 ), and Toll-like receptor (TLR) ligands such as LPS and flagellin through the induction of receptor activator of nuclear factor-κB ligand (RANKL) expression in osteoblasts. CRAMP inhibited the osteoclastogenesis in co-cultures treated with LPS and flagellin, but not in those treated with 1α,25(OH)2 D3 or PGE2 . Although bone marrow macrophages (BMMs) highly expressed formyl peptide receptor 2 (a receptor of CRAMP), CRAMP showed no inhibitory effect on osteoclastogenesis in BMM cultures treated with RANKL. CRAMP suppressed both LPS- and flagellin-induced RANKL expression in osteoblasts and tumour necrosis factor-α (TNF-α) expression in BMMs, suggesting that CRAMP neutralizes the actions of LPS and flagellin. LPS and flagellin enhanced the expression of CRAMP mRNA in osteoblasts. Extracellularly added CRAMP suppressed LPS- and flagellin-induced CRAMP expression. These results suggest that the production of CRAMP promoted by LPS and flagellin is inhibited by CRAMP released by osteoblasts through a feedback regulation. Even though CRAMP itself has no effect on osteoclastogenesis in mice, we propose that CRAMP is an osteoblast-derived protector in bacterial infection-induced osteoclastic bone resorption.
Authors:
Kanji Horibe; Yuko Nakamichi; Shunsuke Uehara; Midori Nakamura; Masanori Koide; Yasuhiro Kobayashi; Naoyuki Takahashi; Nobuyuki Udagawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  140     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-10-07     Completed Date:  2013-12-11     Revised Date:  2014-11-04    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  344-51     Citation Subset:  IM    
Copyright Information:
© 2013 John Wiley & Sons Ltd.
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MeSH Terms
Descriptor/Qualifier:
24,25-Dihydroxyvitamin D 3 / immunology
Animals
Antimicrobial Cationic Peptides / immunology
Bone Marrow Cells / immunology,  metabolism
Bone Resorption / etiology,  immunology*
Cathelicidins / pharmacology,  physiology*
Cells, Cultured
Coculture Techniques
Dinoprostone / immunology
Feedback, Physiological
Flagellin / immunology
Lipopolysaccharides / immunology
Male
Mice
Mice, Inbred Strains
Osteoblasts / drug effects,  immunology*
Osteoclasts / drug effects,  immunology*
Osteogenesis / drug effects,  immunology*
RANK Ligand / genetics,  metabolism
Toll-Like Receptors / agonists
Tumor Necrosis Factor-alpha / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Antimicrobial Cationic Peptides; 0/Cathelicidins; 0/Lipopolysaccharides; 0/RANK Ligand; 0/Toll-Like Receptors; 0/Tumor Necrosis Factor-alpha; 0/cathelicidin antimicrobial peptide; 12777-81-0/Flagellin; 143108-26-3/CAP18 lipopolysaccharide-binding protein; 40013-87-4/24,25-Dihydroxyvitamin D 3; K7Q1JQR04M/Dinoprostone
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