 |
MR Vol.14 No.3 indexに戻る
 |
MODERN RHEUMATOLOGY
Vol.14 No.3 |
 |
|
|
 |
|
|
Ten years in the life of an enzyme: the story
of the human MMP-13 (collagenase-3)
|
|
|
| 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 |
| |
| 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. |
| |
| Key words |
| Arthritis - Cancer - Cartilage - Collagenase-3
- Matrix metalloproteinase (MMP)-13 |
|
|
 |
|
|
