Grant: Operating Grant

Arthritis is a serious and debilitating disease that affects joints, bones and ligaments in 4 million Canadians. Arthritis is one of the major causes of pain and disability in Canada with an economic burden ~$5 billion, i.e. over 10% of the total economic burden of all illnesses. A lack of clinical tests impedes early and clear diagnosis of active vs. remission phases of disease resulting in an inability to provide the best and early treatment. In patients with arthritis, excessive inflammation in an overactive immune system mistakenly attacks healthy joint tissues. This attack leads to inflammation, pain and joint damage where the tissue components are cut by enzymes termed proteases. In arthritis the joint tissue cells and white blood cells make important proteases known as MMPs. MMPs dissolve critical proteins that add strength to joints and tendons. In addition we found in skin that MMP2 removes a block allowing inflammation to proceed. This inflammation pathway, termed complement, is overactive in patients with arthritis. In contrast, we found that MMP8 and MMP12 from the white blood cells dampen inflammation, improving healing and so are beneficial in arthritis. This is a new concept for MMPs that are usually presumed to be destructive. We suggest that inflammatory proteins in arthritis form a diagnostic (biomarker) signature that can be used to predict whether joint destruction is present and active, or in remission. We have developed techniques to identify key inflammatory signature proteins in tissues. Thereby we aim to understand the mechanisms of inflammation in arthritis by comparing healthy joints with arthritic joints from mice lacking MMP2 or white blood cell MMPs. The biomarkers will be developed as a new way to test for arthritis and to assess treatment options. The mechanisms by which some MMPs are protective or destructive will provide clues to develop drugs to treat arthritis, improve the health of Canadians and reduce health care costs.