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Ann Rheum Dis. 1999 November; 58(11): 691–697.
PMCID: PMC1752794

Analysis of 16 different matrix metalloproteinases (MMP-1 to MMP-20) in the synovial membrane: different profiles in trauma and rheumatoid arthritis

Abstract

OBJECTIVE—To define the pattern of mRNA expression of all human matrix metalloproteinases (MMPs) described to date in rheumatoid arthritis (RA) and traumatic synovial membrane, in order to differentiate between a physiological tissue remodelling pattern and that associated with inflammatory tissue destruction.
METHODS—Analysis of SwissProt protein and EMBL/GenBank nucleotide sequence banks, protein sequence alignment, reverse transcriptase-polymerase chain reaction and nucleotide sequencing were used.
RESULTS—MMP-2 (gelatinase A), MMP-3 (stromelysin-1), MMP-11 (stromelysin-3) and MMP-19 were constitutively expressed. MMP-1 (fibroblast type collagenase), MMP-9 (gelatinase B) and MMP-14 (MT1-MMP) were expressed in all RA, but only in 55-80% of trauma samples. MMP-13 (collagenase-3) and MMP-15 (MT2-MMP) were expressed exclusively in RA (80-90% of the samples). MMP-20 (enamelysin) was absent and MMP-8 (collagenase-2) was rarely found in RA or trauma. All other MMPs (-7, -10, -12, -16, -17) had an intermediate pattern of expression.
CONCLUSIONS—Some MMPs without interstitial collagenase activity seem to have a constitutive pattern of expression and probably participate in physiological synovial tissue remodelling. Some MMPs are exclusively associated to RA synovitis, for example, MMP-13, which preferentially degrades type II collagen and aggrecan, and MMP-15, which activates proMMP-2 and proMMP-13 and is involved in tumour necrosis factor α processing. This clear cut rheumatoid/inflammatory MMP profile, more complex than has been previously appreciated, may facilitate inflammatory tissue destruction in RA.

Figure 1
Family tree of the matrix metalloproteinases. Distance along the vertical axis in the family tree is proportional to the difference between sequences. The horizontal distance has no significance.
Figure 2
Reverse transcriptase polymerase chain reaction (RT-PCR) control analysis. (A) Ten synovitis tissue samples from RA patients (lanes 1-10). (B) Nine control non-arthritic knee injury samples (lanes 1-9). In both (A) and (B), the upper panel shows mRNA ...
Figure 3
Reverse transcriptase polymerase chain reaction (RT-PCR) analysis of MMP-1 through MMP-20. (A) Ten synovitis tissue samples from RA patients (lanes 1-10). (B) Nine control non-arthritic knee injury samples (lanes 1-9). Samples are in the same order as ...

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