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Matrix metalloproteinase-13 expression in response to double-stranded RNA in human chondrocytes.
MedLine Citation:
PMID:  23334990     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVES: To investigate the mechanism of matrix metalloproteinase (MMP)-13 expression in chondrocytes via pattern recognition receptors (PRRs) for double-stranded (ds) RNA. METHODS: Differential expression of PRRs was determined by real-time RT-PCR of RNA from osteoarthritis (OA) and neck of femur (NOF) fracture patients. Isolated human articular chondrocytes and the chondrosarcoma cell-line SW1353 were activated with different molecular sized poly(I:C) as a dsRNA mimic, and gene expression and protein changes monitored by real-time RT-PCR and immunoblotting, respectively. RESULTS: dsRNA-signalling moieties 'Toll-like receptor 3' (TLR3), 'retinoid-inducible gene 1' (RIG-I) and 'nucleotide-binding oligomerization domain, leucine rich repeat containing X1' (NLRX1) were all differentially expressed in our OA versus NOF expression screen. Depletion of the dsRNA-sensing receptors TLR3, RIG-I or 'Melanoma differentiation-associated gene-5' (MDA5) suppressed the induction of MMP13 by poly(I:C), regardless of its delivery. Additionally, depletion of the downstream transcription factor interferon regulatory factor 3 (IRF3) resulted in reduced induction of MMP13 by poly(I:C). CONCLUSIONS: dsRNA-signalling in chondrocytes requires a range of PRRs including TLR3, RIG-I and MDA5 for the full-induction of MMP13, thus providing tight regulation of a gene critical for maintenance of cartilage integrity. Our data add to the understanding of MMP13 regulation, which is essential before such mechanisms can be exploited to alleviate the cartilage destruction associated with OA.
Authors:
Marta Radwan; Christos Gavriilidis; John H Robinson; Rose Davidson; Ian M Clark; Andrew D Rowan; David A Young
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-17
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  -     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 by the American College of Rheumatology.
Affiliation:
Musculoskeletal Research Group, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle-upon-Tyne, NE2 4HH,UK.
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