Exp Mol Med.  2012 Sep;44(9):529-535.

Over-expression of extracellular superoxide dismutase in mouse synovial tissue attenuates the inflammatory arthritis

Affiliations
  • 1School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 702-701, Korea. jaewoong64@hanmail.net
  • 2Hormel Institute, University of Minnesota, Minnesota 55912, USA.
  • 3Department of Physics, Kyungpook National University, Daegu 702-701, Korea.
  • 4Department of BT, Kyungpook National University, Sangju 742-711, Korea.
  • 5Regenerative Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea. jwlee@kribb.re.kr

Abstract

Oxidative stress such as reactive oxygen species (ROS) within the inflamed joint have been indicated as being involved as inflammatory mediators in the induction of arthritis. Correlations between extracellular-superoxide dismutase (EC-SOD) and inflammatory arthritis have been shown in several animal models of RA. However, there is a question whether the over-expression of EC-SOD on arthritic joint also could suppress the progression of disease or not. In the present study, the effect on the synovial tissue of experimental arthritis was investigated using EC-SOD over-expressing transgenic mice. The over-expression of EC-SOD in joint tissue was confirmed by RT-PCR and immunohistochemistry. The degree of the inflammation in EC-SOD transgenic mice was suppressed in the collagen-induced arthritis model. In a cytokine assay, the production of pro-inflammatory cytokines such as, IL-1beta, TNFalpha, and matrix metalloproteinases (MMPs) was decreased in fibroblast-like synoviocyte (FLS) but not in peripheral blood. Histological examination also showed repressed cartilage destruction and bone in EC-SOD transgenic mice. In conclusion, these data suggest that the over-expression of EC-SOD in FLS contributes to the activation of FLS and protection from joint destruction by depressing the production of the pro-inflammatory cytokines and MMPs. These results provide EC-SOD transgenic mice with a useful animal model for inflammatory arthritis research.

Keyword

arthritis, experimental; reactive oxygen species; rheumatoid arthritis; superoxide dismutase; synovial membrane

MeSH Terms

Animals
Arthritis, Experimental/blood/*enzymology/metabolism
*Arthritis, Rheumatoid/enzymology/pathology
Fibroblasts/metabolism
Gene Expression Regulation
Inflammation/pathology
Interleukin-1beta/blood/metabolism
Joints/enzymology/pathology
Matrix Metalloproteinases/blood/metabolism
Mice
Mice, Transgenic
Reactive Oxygen Species/metabolism
*Superoxide Dismutase/genetics/metabolism
Synovial Fluid/*enzymology
Synovial Membrane/pathology
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