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Characterisation of the cell type-specificity of collagenase 3 mRNA expression in comparison with membrane type 1 matrix metalloproteinase and gelatinase A in the synovial membrane in rheumatoid arthritis
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  1. P K Petrow1,
  2. D Wernicke2,
  3. C Schulze Westhoff2,
  4. K M Hummel3,
  5. R Bräuer1,
  6. J Kriegsmann4,
  7. E Gromnica-Ihle5,
  8. R E Gay6,
  9. S Gay6
  1. 1Institute of Pathology, University of Jena, Germany
  2. 2Max-Delbrück-Centre for Molecular Medicine, Berlin-Buch, Germany
  3. 3Department of Nephrology and Rheumatology, University of Göttingen, Germany
  4. 4Institute of Pathology, University of Mainz, Germany
  5. 5Clinic of Rheumatology, Berlin-Buch, Germany
  6. 6University Hospital of Zürich, Zürich, Switzerland
  1. Correspondence to:
    Dr P K Petrow, Institute of Pathology, University of Jena, Ziegelmühlenweg 1, D-07740 Jena, Germany;
    peterpetrow{at}excite.com

Abstract

Objective: To study the pattern and cell type-specificity of collagenase 3, membrane-type 1 matrix metalloproteinase (MT1-MMP), and gelatinase A mRNA expression in the synovial membrane in rheumatoid arthritis (RA).

Methods: The mRNA expression of collagenase 3, MT1-MMP, and gelatinase A was characterised by northern blot analysis, reverse transcriptase-polymerase chain reaction, and in situ hybridisation. In situ hybridisation was performed in combination with the immunohistochemical detection of cell type-specific antigens.

Results: Synovial membrane specimens from 19 of 21 patients with RA expressing collagenase 3 mRNA were positive for MT1-MMP and gelatinase A mRNA. In control samples from patients without destructive inflammatory joint diseases collagenase 3 mRNA was not expressed and only in two of seven cases was a coexpression of MT1-MMP and gelatinase A mRNA detected. Fibroblast-like cells of the synovial membrane were found to be the predominant source of collagenase 3, MT1-MMP, and gelatinase A mRNA expression in lining and sublining layers as well as at the synovial membrane-cartilage interface. Additionally, the expression of MT1-MMP mRNA was detected in endothelial cells. Collagenase 3 mRNA expression was found in about 5% of CD68 positive macrophages.

Conclusions: Collagenase 3 mRNA is expressed simultaneously with MT1-MMP and gelatinase A mRNA in fibroblast-like cells of the synovial membrane in RA. These results suggest (a) a broad extracellular proteolytic potential of fibroblast-like cells and (b) an important role of cell surface associated procollagenase 3 activation by MT1-MMP and gelatinase A for cartilage degradation by invading fibroblast-like cells.

  • synovial fibroblasts
  • matrix metalloproteinases
  • cartilage degradation
  • APAAP, alkaline phosphatase-anti-alkaline phosphatase
  • GAPDH, glyceraldehyde-3-phosphate dehydrogenase
  • mAb, monoclonal antibody
  • MT1-MMP, membrane-type 1 matrix metalloproteinase
  • NBT/BCIP, nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolylphosphate
  • RA, rheumatoid arthritis
  • RT-PCR, reverse transcriptase-polymerase chain reaction
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Footnotes

  • P K Petrow and D Wernicke contributed equally to the work.

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