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MODERN RHEUMATOLOGY Vol.14 No.3
>MR14-3
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Ten years in the life of an enzyme: the story of the human MMP-13 (collagenase-3)
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| Ginette Tardif1, Pascal Reboul1, Jean-Pierre Pelletier1 and Johanne Martel-Pelletier1 |
| (1) Osteoarthritis Research Unit, Hopital Notre-Dame, Centre hospitalier de lUniversite de Montreal, 1560 Sherbrooke Street East, Montreal, Quebec, H2L 4M1, Canada |
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Abstract |
| In 1994, a new human matrix metalloproteinase (MMP) was identified and cloned. This enzyme displayed the structural characteristics of a collagenase and was named collagenase-3, or MMP-13 according to MMP nomenclature. This review describes the research advances in the understanding of the function/production of the human MMP-13 at the tissular, cellular, biochemical, and molecular levels. In contrast to many human MMPs, the MMP-13 distribution pattern is restrictive in normal tissues and selective in pathological conditions. This enzyme plays a premier role in tissue remodeling as well as in some pathological processes such as cancer and arthritis. MMP-13 demonstrates versatility in its substrate utilization. In addition to being highly active on type II collagen, MMP-13 cleaves other substrates, mostly macromolecules of the extracellular matrix, but also molecules such as connective tissue (CTGF) and fibrinogen. MMP-13 is controlled at multiple levels: i.e., the expression/synthesis, activation, and inhibition of the active enzyme. Unlike other MMPs, the human MMP-13 gene is transcribed into several transcripts which could yield proteins with activities and functions different from those of the original MMP-13. Activation of MMP-13 involves a proteolytic cascade including MMP-14 (MT1-MMP) and MMP-2. Transcription is regulated by numer-ous agents, mostly by growth factors, proinflammatory cytokines and mechanical stimuli. Cloning of the MMP-13 promoter revealed the presence of a number of binding sites implicated in transcriptional regulation: TATA box, AP-1, PEA-3, OSE-2, and the newly identified negative regulator, AGRE. MMP-13 constitutes a more complex system than was originally thought. Although our knowledge of MMP-13 biochemistry and regulation has greatly increased over the years, there is still much to discover. |
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| Key words |
| Arthritis - Cancer - Cartilage - Collagenase-3 - Matrix metalloproteinase (MMP)-13 |
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