Joint Diseases and Matrix Metalloproteinases: A Role for MMP-13
Hironari Takaishi, Tokuhiro Kimura, Seema Dalal, Yasunori Okada and Jeanine D'Armiento
Affiliation: Departments of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan.
The role of matrix metalloproteinases in disease has been investigated over the last two decades. A focus on this family of proteases is particularly emphasized in two major arthritides in humans, osteoarthritis and rheumatoid arthritis. Early work described the presence of multiple MMP family members in the joint of the disease state and recent advances in the development of new knockout mice and disease models have allowed investigators to directly test the role of the MMP proteases in arthritis. MMP-13 is expressed by chondrocytes and synovial cells in human OA and RA and is thought to play a critical role in cartilage destruction. The recent development of an MMP-13 knockout mouse has documented the important role for this enzyme in cartilage formation and further studies under disease conditions promise to reveal the function of this enzyme in disease pathology. This review describes a body of research that supports the development of novel selective MMP-13 inhibitors with the hope of developing these compounds in clinical trials for the treatment of arthritis.
Keywords: human osteoarthritis, proMMP-1, MMP-13 knockout mice, Bone resorption, nonspecific MMP inhibitors
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