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MMP expression in rheumatoid inflammation: the rs11568818 polymorphism is associated with MMP-7 expression at an

M G Kazantseva1, N A Hung, J Highton

  • 1Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.

Genes and Immunity
|January 25, 2013
PubMed

Insights

Matrix metalloproteinases (MMPs) contribute to rheumatoid arthritis (RA) tissue damage. This study found MMP-1 and MMP-3 are widespread, while MMP-12 and MMP-7 expression in nodules link to inflammation and genetic factors.

Area of Science:

  • Immunology
  • Molecular Biology
  • Rheumatology

Background:

  • Matrix metalloproteinases (MMPs) are implicated in joint damage in rheumatoid arthritis (RA).
  • The role of MMPs in extra-articular inflammation in RA is less understood.
  • Specific MMPs (MMP-1, MMP-3, MMP-7, MMP-12) were investigated for their contribution to RA tissue destruction.

Purpose of the Study:

  • To compare the gene expression of MMP-1, MMP-3, MMP-7, and MMP-12 in joint synovia and subcutaneous rheumatoid nodules.
  • To determine the relative contribution of these MMPs to joint and extra-articular tissue destruction and inflammation in RA.
  • To explore associations between MMP expression, genetic polymorphisms, and clinical features in RA patients.

Main Methods:

  • Gene expression analysis of MMP-1, MMP-3, MMP-7, and MMP-12 in synovial tissue and rheumatoid nodules from RA patients.
  • Comparison of MMP expression levels between joint and extra-articular sites.
  • Investigation of the association between MMP-7 expression, the single-nucleotide polymorphism (SNP) rs11568818, and inflammatory markers.

Main Results:

  • MMP-1 and MMP-3 expression predominated in synovial tissues.
  • MMP-12 expression was significantly higher in rheumatoid nodules.
  • Elevated MMP-7 expression in nodules was linked to monocyte/macrophage infiltration, the rs11568818 SNP, and more active inflammation, correlating with earlier RA onset.

Conclusions:

  • MMP-1 and MMP-3 expression is relatively consistent across joint and extra-articular RA tissues.
  • MMP-12 expression in nodules indicates monocyte/macrophage involvement in RA inflammation.
  • The rs11568818 SNP's impact on MMP-7 expression appears specific to nodules, suggesting a role in monocyte/macrophage-mediated inflammatory processes in RA.

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