Abstract
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
Current Pharmaceutical Biotechnology
Title: Joint Diseases and Matrix Metalloproteinases: A Role for MMP-13
Volume: 9 Issue: 1
Author(s): Hironari Takaishi, Tokuhiro Kimura, Seema Dalal, Yasunori Okada and Jeanine D'Armiento
Affiliation:
Keywords: human osteoarthritis, proMMP-1, MMP-13 knockout mice, Bone resorption, nonspecific MMP inhibitors
Abstract: 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.
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Cite this article as:
Takaishi Hironari, Kimura Tokuhiro, Dalal Seema, Okada Yasunori and D'Armiento Jeanine, Joint Diseases and Matrix Metalloproteinases: A Role for MMP-13, Current Pharmaceutical Biotechnology 2008; 9 (1) . https://dx.doi.org/10.2174/138920108783497659
DOI https://dx.doi.org/10.2174/138920108783497659 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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