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Arthritis: What Wnt wrong?

The cellular signaling protein Wnt, which is involved in embryonic development and cancer, contributes to disease progression of both rheumatoid arthritis and osteoarthritis. The article by Nakamura et al., "Expression profiles and functional analyses of Wnt-related genes in human joint disorders," appears in the July issue of The American Journal of Pathology and is accompanied by a commentary.

Wnt is best known as a proto-oncogene because its disruption can lead to cancer in various organs such as colon, lung, and breast. However, mounting evidence also points to its involvement in arthritic joint disease. Comprehensive analysis of the entire Wnt gene family in the progression of arthritis has been lacking until now.

Researchers at Shinshu University School of Medicine in Nagano, Japan, examined 19 members of the Wnt gene family to determine exactly which of these genes were involved in arthritic joint disease. This extensive study, performed under the direction of Dr. Shigeyuki Wakitani, who is an assistant professor at the Department of Orthopedic Surgery, Shinshu University School of Medicine, examined joint tissue from patients who underwent total knee replacement for rheumatoid arthritis (RA), osteoarthritis (OA), or non-arthritic injury.

Using several molecular methods, Wakitani's group identified Wnt-7b and -10a as genes that were significantly upregulated in the arthritic knee tissues. However, protein expression studies revealed that only Wnt-7b was produced in arthritic joints, with strong protein localization to the synovium (or joint lining) and weak localization to cartilage and bone. In addition, strong Wnt-7b expression most frequently correlated with areas of high inflammation.

The authors also examined whether inflammatory cytokines were produced in primary cartilage and synovial cells from arthritic versus normal joints. While OA cells did not differ from controls, primary RA cells produced TNF-a, IL-
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Contact: George Stamatis
gxs18@po.cwru.edu
216-368-3635
American Journal of Pathology
22-Jun-2005


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