Document Detail


Mechanical stretch regulates the expression of matrix metalloproteinase in rheumatoid arthritis fibroblast-like synoviocytes.
MedLine Citation:
PMID:  19296301     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mechanical stretch plays a crucial role in articular joints. In rheumatoid arthritis (RA), it is well known that fibroblast-like synoviocytes (FLS) produce matrix metalloproteinases (MMPs), resulting in local invasion into and degradation of bone and cartilage. We sought to examine whether mechanical stretch regulates the expression and underlying signal pathways of MMP secretion (MMP-1, -3, -13) in RA-FLS. FLS were grown on elastic silicone membrane in an equibiaxial strain apparatus and were exposed to 6% mechanical stretch (equivalent to gentle stretch exercise) for 15 min and 75 min, respectively. Semiquantitative PCR and real-time PCR were used to measure and analyze gene expression. Protein levels were determined by Western blotting. The results showed that 15 min of mechanical stretch inhibited MMP-1 and MMP-13 mRNA and protein level. However, the degree of inhibition by 75 min of stretch in expression of MMP-1 and MMP-13 was lower compared with 15 min stretch groups. The mRNA expression of ERK-1, ets-1 and citied-2 were increased by 6% mechanical stretch under both time points, however c-jun and c-fos mRNA level were affected differently after 15 min and 75 min mechanical stretch compared to control group. There were no significant changes on MMP-3 and ets-2 mRNA level under both 6% mechanical stretch time points. In the presence of pro-inflammatory cytokines (IL-1beta and TNF-alpha), the stretch also reduced the mRNA expression of MMP-1 and MMP-13. In short, our results showed that gentle mechanical strain affects MMP-1 and MMP-13 expression, potentially through the ERK-1-ets-1-cited-2-c-jun signaling pathway.
Authors:
Ping Wang; Li Yang; Xin You; Gurinder K Singh; Lei Zhang; Yan Yan; K L Paul Sung
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Connective tissue research     Volume:  50     ISSN:  1607-8438     ISO Abbreviation:  Connect. Tissue Res.     Publication Date:  2009  
Date Detail:
Created Date:  2009-03-19     Completed Date:  2009-05-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0365263     Medline TA:  Connect Tissue Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  98-109     Citation Subset:  IM    
Affiliation:
College of Bioengineering, Chongqing University, Chongqing, China.
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MeSH Terms
Descriptor/Qualifier:
Arthritis, Rheumatoid / enzymology*,  pathology,  physiopathology
Blotting, Western
Fibroblasts / drug effects,  enzymology*
Gene Expression Regulation
Humans
Interleukin-1beta / pharmacology
Matrix Metalloproteinases / genetics,  metabolism*
Mechanotransduction, Cellular / physiology*
Mitogen-Activated Protein Kinase 3 / genetics,  metabolism
Proto-Oncogene Protein c-ets-1 / genetics,  metabolism
RNA, Messenger / metabolism
Recombinant Proteins / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Stress, Mechanical
Synovial Membrane / drug effects,  enzymology*
Tumor Necrosis Factor-alpha / pharmacology
Chemical
Reg. No./Substance:
0/ETS1 protein, human; 0/Interleukin-1beta; 0/Proto-Oncogene Protein c-ets-1; 0/RNA, Messenger; 0/Recombinant Proteins; 0/Tumor Necrosis Factor-alpha; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 3.4.24.-/Matrix Metalloproteinases

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


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