• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of annrheumdAnnals of the Rheumatic DiseasesCurrent TOCInstructions for authors
Ann Rheum Dis. Nov 1999; 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.

Full Text

The Full Text of this article is available as a PDF (2.6M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Springman EB, Angleton EL, Birkedal-Hansen H, Van Wart HE. Multiple modes of activation of latent human fibroblast collagenase: evidence for the role of a Cys73 active-site zinc complex in latency and a "cysteine switch" mechanism for activation. Proc Natl Acad Sci U S A. 1990 Jan;87(1):364–368. [PMC free article] [PubMed]
  • Evanson JM, Jeffrey JJ, Krane SM. Human collagenase: identification and characterization of an enzyme from rheumatoid synovium in culture. Science. 1967 Oct 27;158(3800):499–502. [PubMed]
  • Chatham WW, Heck LW, Blackburn WD., Jr Lysis of fibrillar collagen by neutrophils in synovial fluid. A role for surface-bound immunoglobulins. Arthritis Rheum. 1990 Sep;33(9):1333–1339. [PubMed]
  • Konttinen YT, Lindy O, Kemppinen P, Saari H, Suomalainen K, Vauhkonen M, Lindy S, Sorsa T. Collagenase reserves in polymorphonuclear neutrophil leukocytes from synovial fluid and peripheral blood of patients with rheumatoid arthritis. Matrix. 1991 Aug;11(4):296–301. [PubMed]
  • Case JP, Lafyatis R, Remmers EF, Kumkumian GK, Wilder RL. Transin/stromelysin expression in rheumatoid synovium. A transformation-associated metalloproteinase secreted by phenotypically invasive synoviocytes. Am J Pathol. 1989 Dec;135(6):1055–1064. [PMC free article] [PubMed]
  • Okada Y, Takeuchi N, Tomita K, Nakanishi I, Nagase H. Immunolocalization of matrix metalloproteinase 3 (stromelysin) in rheumatoid synovioblasts (B cells): correlation with rheumatoid arthritis. Ann Rheum Dis. 1989 Aug;48(8):645–653. [PMC free article] [PubMed]
  • Stolow MA, Bauzon DD, Li J, Sedgwick T, Liang VC, Sang QA, Shi YB. Identification and characterization of a novel collagenase in Xenopus laevis: possible roles during frog development. Mol Biol Cell. 1996 Oct;7(10):1471–1483. [PMC free article] [PubMed]
  • Cossins J, Dudgeon TJ, Catlin G, Gearing AJ, Clements JM. Identification of MMP-18, a putative novel human matrix metalloproteinase. Biochem Biophys Res Commun. 1996 Nov 12;228(2):494–498. [PubMed]
  • Pendás AM, Balbín M, Llano E, Jiménez MG, López-Otín C. Structural analysis and promoter characterization of the human collagenase-3 gene (MMP13). Genomics. 1997 Mar 1;40(2):222–233. [PubMed]
  • Feng DF, Doolittle RF. Progressive sequence alignment as a prerequisite to correct phylogenetic trees. J Mol Evol. 1987;25(4):351–360. [PubMed]
  • Higgins DG, Sharp PM. Fast and sensitive multiple sequence alignments on a microcomputer. Comput Appl Biosci. 1989 Apr;5(2):151–153. [PubMed]
  • Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. [PubMed]
  • Llano E, Pendás AM, Knäuper V, Sorsa T, Salo T, Salido E, Murphy G, Simmer JP, Bartlett JD, López-Otín C. Identification and structural and functional characterization of human enamelysin (MMP-20). Biochemistry. 1997 Dec 9;36(49):15101–15108. [PubMed]
  • Kristo P, Saarelainen R, Fagerström R, Aho S, Korhola M. Protein purification, and cloning and characterization of the cDNA and gene for xylose isomerase of barley. Eur J Biochem. 1996 Apr 1;237(1):240–246. [PubMed]
  • Konttinen YT, Bergroth V, Nordström D, Koota K, Skrifvars B, Hagman G, Friman C, Hämäläinen M, Slätis P. Cellular immunohistopathology of acute, subacute, and chronic synovitis in rheumatoid arthritis. Ann Rheum Dis. 1985 Aug;44(8):549–555. [PMC free article] [PubMed]
  • Makino Y, Tanaka H, Makino I. Paradoxical derepression of collagenase gene expression by the antirheumatic gold compound aurothiomalate. Mol Pharmacol. 1994 Dec;46(6):1084–1089. [PubMed]
  • Firestein GS, Paine MM, Boyle DL. Mechanisms of methotrexate action in rheumatoid arthritis. Selective decrease in synovial collagenase gene expression. Arthritis Rheum. 1994 Feb;37(2):193–200. [PubMed]
  • Lohi J, Kähäri VM, Keski-Oja J. Cyclosporin A enhances cytokine and phorbol ester-induced fibroblast collagenase expression. J Invest Dermatol. 1994 Jun;102(6):938–944. [PubMed]
  • Strongin AY, Collier I, Bannikov G, Marmer BL, Grant GA, Goldberg GI. Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloprotease. J Biol Chem. 1995 Mar 10;270(10):5331–5338. [PubMed]
  • Aimes RT, Quigley JP. Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments. J Biol Chem. 1995 Mar 17;270(11):5872–5876. [PubMed]
  • Konttinen YT, Ceponis A, Takagi M, Ainola M, Sorsa T, Sutinen M, Salo T, Ma J, Santavirta S, Seiki M. New collagenolytic enzymes/cascade identified at the pannus-hard tissue junction in rheumatoid arthritis: destruction from above. Matrix Biol. 1998 Dec;17(8-9):585–601. [PubMed]
  • Imai K, Ohta S, Matsumoto T, Fujimoto N, Sato H, Seiki M, Okada Y. Expression of membrane-type 1 matrix metalloproteinase and activation of progelatinase A in human osteoarthritic cartilage. Am J Pathol. 1997 Jul;151(1):245–256. [PMC free article] [PubMed]
  • Cole AA, Chubinskaya S, Schumacher B, Huch K, Szabo G, Yao J, Mikecz K, Hasty KA, Kuettner KE. Chondrocyte matrix metalloproteinase-8. Human articular chondrocytes express neutrophil collagenase. J Biol Chem. 1996 May 3;271(18):11023–11026. [PubMed]
  • Hanemaaijer R, Sorsa T, Konttinen YT, Ding Y, Sutinen M, Visser H, van Hinsbergh VW, Helaakoski T, Kainulainen T, Rönkä H, et al. Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial cells. Regulation by tumor necrosis factor-alpha and doxycycline. J Biol Chem. 1997 Dec 12;272(50):31504–31509. [PubMed]
  • Lindy O, Konttinen YT, Sorsa T, Ding Y, Santavirta S, Ceponis A, López-Otín C. Matrix metalloproteinase 13 (collagenase 3) in human rheumatoid synovium. Arthritis Rheum. 1997 Aug;40(8):1391–1399. [PubMed]
  • Imai S, Konttinen YT, Jumppanen M, Lindy O, Ceponis A, Kemppinen P, Sorsa T, Santavirta S, Xu JW, Lopéz-Otín C. High levels of expression of collagenase-3 (MMP-13) in pathological conditions associated with a foreign-body reaction. J Bone Joint Surg Br. 1998 Jul;80(4):701–710. [PubMed]
  • Uría JA, Ståhle-Bäckdahl M, Seiki M, Fueyo A, López-Otín C. Regulation of collagenase-3 expression in human breast carcinomas is mediated by stromal-epithelial cell interactions. Cancer Res. 1997 Nov 1;57(21):4882–4888. [PubMed]
  • Pendás AM, Knäuper V, Puente XS, Llano E, Mattei MG, Apte S, Murphy G, López-Otín C. Identification and characterization of a novel human matrix metalloproteinase with unique structural characteristics, chromosomal location, and tissue distribution. J Biol Chem. 1997 Feb 14;272(7):4281–4286. [PubMed]
  • Tardif G, Pelletier JP, Dupuis M, Hambor JE, Martel-Pelletier J. Cloning, sequencing and characterization of the 5'-flanking region of the human collagenase-3 gene. Biochem J. 1997 Apr 1;323(Pt 1):13–16. [PMC free article] [PubMed]
  • d'Ortho MP, Will H, Atkinson S, Butler G, Messent A, Gavrilovic J, Smith B, Timpl R, Zardi L, Murphy G. Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases. Eur J Biochem. 1997 Dec 15;250(3):751–757. [PubMed]
  • Kolkenbrock H, Hecker-Kia A, Orgel D, Ulbrich N, Will H. Activation of progelatinase A and progelatinase A/TIMP-2 complex by membrane type 2-matrix metalloproteinase. Biol Chem. 1997 Feb;378(2):71–76. [PubMed]

Figures and Tables

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 ...

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Group

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...