MMP-3 (also referred to as stromelysin-1) may be expressed in fibroblasts, chondrocytes,
endothelial cells, macrophages, vascular smooth muscle cells, osteoblasts, and keratinocytes
in response to appropriate stimuli (3). Various agents regulate its biosynthesis. Inflammatory
cytokines such as IL-1 and TNF-alpha, epidermal growth factor, platelet-derived growth factor,
phorbol and oncogenic cellular transformation are the inductive agents. In comparison,
retinoic acid, glucocorticoids, estrogen, progesterone and TGF-beta suppress MMP-3 synthesis.
MMP-3 is secreted from the cells as a proenzyme. The proenzyme has been shown to stimulate
plasminogen activation (4). The N-terminal pro-domain contains the cysteine switch motif
conserved in MMPs that maintains MMP-3 in the latent state (5). Activation of the proenzyme
results in the removal of the pro-domain. MMP-3 activation can be achieved in vitro by
proteases such as itself, chyrotrypsin, neutrophil elastase and plasma kallikrein, and by mercury
compounds (3). The resulting active enzyme consists of a catalytic domain with a zinc-binding
motif conserved in metzincins (6,7). A short hinge peptide links the catalytic domain to the
C-terminal hemopexin-like domain. The active MMP-3 is capable of cleaving types III, IV, IX and
X collagen, aggrecan, fibronectin, laminin, IGFBP-3, serpins, and IL-1 beta. The active enzyme also
activates proMMP-1, -8, -9, and -13. Therefore, it is suggested that MMP-3 may participate in
physiological matrix turnover and pathological destruction of the tissue. For example, MMP-3
is required for the generation of a macrophage chemoattractant in a model of herniated disc
resorption (8).
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