Document Detail

The inhibitory effect of microRNA-146a expression on bone destruction in collagen-induced arthritis.
MedLine Citation:
PMID:  21425254     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: MicroRNA, a class of noncoding RNA, play a role in human diseases. MicroRNA-146a (miR-146a) is a negative regulator of immune and inflammatory responses, and is strongly expressed in rheumatoid arthritis (RA) synovium and peripheral blood mononuclear cells (PBMCs). This study was undertaken to examine whether miR-146a expression inhibits osteoclastogenesis, and whether administration of miR-146a prevents joint destruction in mice with collagen-induced arthritis (CIA).
METHODS: PBMCs from healthy volunteers were isolated and seeded in culture plates. The following day, double-stranded miR-146a was transfected and cultured in the presence of macrophage colony-stimulating factor and either tumor necrosis factor α or RANKL. After 3 weeks, tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells were counted. Three days after miR-146a culture, the expression of c-Jun, nuclear factor of activated T cells c1 (NF-ATc1), PU.1, and TRAP was evaluated by quantitative reverse transcriptase-polymerase chain reaction. After the onset of distinct arthritis in mice with CIA, double-stranded miR-146a or nonspecific double-stranded RNA was administered twice by intravenous injection. Radiographic and histologic examinations were performed at 4 weeks.
RESULTS: The number of TRAP-positive multinucleated cells in human PBMCs was significantly reduced by miR-146a in a dose-dependent manner. The expression of c-Jun, NF-ATc1, PU.1, and TRAP in PBMCs was significantly down-regulated by miR-146a. Administration of miR-146a prevented joint destruction in mice with CIA, although it did not completely ameliorate inflammation.
CONCLUSION: Our findings indicate that expression of miR-146a inhibits osteoclastogenesis and that administration of double-stranded miR-146a prevents joint destruction in arthritic mice. Administration of miR-146a has potential as a novel therapeutic target for bone destruction in RA.
Tomoyuki Nakasa; Hayatoshi Shibuya; Yoshihiko Nagata; Takuya Niimoto; Mitsuo Ochi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  63     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-01     Completed Date:  2011-08-17     Revised Date:  2011-08-29    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1582-90     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 by the American College of Rheumatology.
Department of Orthopaedic Surgery, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
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MeSH Terms
Acid Phosphatase / biosynthesis
Arthritis, Experimental / therapy*
Bone Resorption / therapy*
Cells, Cultured
Coculture Techniques
Isoenzymes / biosynthesis
JNK Mitogen-Activated Protein Kinases / biosynthesis
Leukocytes, Mononuclear / transplantation
Macrophage Colony-Stimulating Factor / pharmacology
MicroRNAs / administration & dosage*,  genetics*
NFATC Transcription Factors / biosynthesis
Proto-Oncogene Proteins / biosynthesis
RANK Ligand / pharmacology
RNA, Double-Stranded / administration & dosage,  genetics
Trans-Activators / biosynthesis
Tumor Necrosis Factor-alpha / pharmacology
Reg. No./Substance:
0/Isoenzymes; 0/MIRN146 microRNA, human; 0/MicroRNAs; 0/NFATC Transcription Factors; 0/Proto-Oncogene Proteins; 0/RANK Ligand; 0/RNA, Double-Stranded; 0/Trans-Activators; 0/Tumor Necrosis Factor-alpha; 0/proto-oncogene protein Spi-1; 81627-83-0/Macrophage Colony-Stimulating Factor; EC Mitogen-Activated Protein Kinases; EC 3.1.3.-/tartrate-resistant acid phosphatase; EC Phosphatase
Comment In:
Immunotherapy. 2011 Jul;3(7):829-31   [PMID:  21751952 ]

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