Arthritis and the Wnt Factor

An article by Nakamura et al., "Expression profiles and functional analyses of Wnt-related genes in human joint disorders," will appear in the July issue of The American Journal of Pathology. The article revolves around the protein, Wnt. Wnt is a proto-oncogene since its disruption can lead to cancer in various organs. But current evidence might show that it is also involved in arthritic joint disease.

At present a through analysis of the Wnt gene family has been pending towards the progression of arthritis. A group of researchers at Shinshu University in Nagano, Japan have examined 19 members of the Wnt gene family. There study is to find out which gene is involved in arthritic joint disease. The study is being performed under the supervision of the assistant professor at the Department of Orthopedic Surgery, Dr, Shingeyuki Wakitani. The study also includes examination of joint tissues from patients who have undergone total knee replacements for rheumatoid arthritis (RA), osteoarthritis (OA), or non-arthritic injury.

The group had identified certain genes, which were upregulated in the arthritic knee tissues. These were Wnt-7b and Wnt –10a. The above was found with molecular methods, while protein expression studies reveal 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.

The author also examines 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-1ß and IL-6 at levels 2- to 4-fold above controls. Importantly, this effect could be replicated in normal cells when they were engineered to express Wnt-7b, demonstrating the importance of Wnt-7b in the inflammatory response of RA.

Wnt-7b was noticed to be strongly upregulated within joints at sites of disease manifestation mainly in synovium of RA but in synovium, cartilage, osteophyte, and bone of OA. Also findings show that Wnt-7b was recurrently found at sites of inflammation and elicited an inflammatory response, which are consistent with inflammation as a hallmark of RA disease.

This identifies Wnt-7b processing a role in arthritic processes. Arthritic diseases are known to manifest differently depending on the type, with RA displaying inflammation to the synovium and loss of cartilage and bone, and OA exhibiting a narrowing of joint space, loss of protective cartilage, and growth of bone cysts.