Ann Rheum Dis 1999;58:691-697 ( November )

Extended report

Analysis of 16 different matrix metalloproteinases (MMP-1 to MMP-20) in the synovial membrane: different profiles in trauma and rheumatoid arthritis Yrjö T Konttinen^{a b}, Mia Ainola, Heikki Valleala^b, Jian Ma^b, Hideo Ida^c, Jami Mandelin^b, Raimund W Kinne^d, Seppo Santavirta^e, Timo Sorsa^f, Carlos López-Otín^g, Michiaki Takagi^c

^a Department of Oral Medicine, University of Helsinki, Finland, ^b Department of Medicine, Helsinki University Central Hospital and Department of Anatomy, University of Helsinki, Finland, ^c Department of Orthopaedic Surgery, Yamagata University School of Medicine, Yamagata, Japan, ^d Experimental Rheumatology, Friedrich-Schiller-University, Jena, Germany, ^e Department of Orthopaedics and Traumatology, Helsinki University Central Hospital, Helsinki, Finland, ^f Department of Periodontology, University of Helsinki, Finland, ^g University of Oviedo, Oviedo, Spain

Correspondence to: Dr Y T Konttinen, Institute of Biomedicine, Department of Anatomy, PO Box 9 (Siltavuorenpenger 20 A), FIN-00014 University of Helsinki, Finland.

Accepted for publication 19 June 1999

OBJECTIVETo 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.
METHODSAnalysis of SwissProt protein and EMBL/GenBank nucleotide sequence banks, protein sequence alignment, reverse transcriptase-polymerase chain reaction and nucleotide sequencing were used.
RESULTSMMP-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.
CONCLUSIONSSome 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  processing. This clear cut rheumatoid/inflammatory MMP profile, more complex than has been previously appreciated, may facilitate inflammatory tissue destruction in RA.

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© 1999 by Annals of the Rheumatic Diseases
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