IDENTIFICATION OF MEMBRANE-TYPE 1 MATRIX METALLOPROTEINASE AS A NOVEL THERAPEUTIC TARGET OF RHEUMATOID ARTHRITIS

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Rheumatoid arthritis (RA) is a systemic autoimmune disease whose key pathological features is destruction of joint tissues including cartilage. Our recent data indicated that a cell membrane-anchored protein degrading enzyme termed, MT1-MMP, plays an essential role in cartilage erosion in RA. We hypothesize that specific inhibition of MT1-MMP can be a potential RA treatment. We propose to address this by assessing the effect of MT1-MMP inhibition in RA progression in a collagen-induced arthritis (CIA) in transgenic mice that express a dominant negative inhibitor of MT1-MMP. We will also analyze the effect of a MT1-MMP-specific inhibitory antibody in mice with CIA. Completing the proposed work would establish MT1-MMP as a novel therapeutic target of RA treatment, which may lead into development of novel RA therapy in the future.