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THU0101 Highly elevated levels of the disintegrin metalloproteinase mdc15 in rheumatoid synovial membranes
  1. B Böhm1,
  2. T Aigner2,
  3. CP Blobel3,
  4. JR Kalden1,
  5. H Burkhardt1
  1. 1Internal Medicine III, Clinical Immunology and Rheumatology, Erlangen, Germany
  2. 2Institute of Pathology, Cartilage Research Group, Erlangen, Germany
  3. 3Memorial Sloan Kettering Cancer Institute, New York, USA

Abstract

Background MDC15 (ADAM15) belongs to the family of membrane-bound disintegrin metalloproteinases (ADAM or MDC; a disintegrin and metalloproteinase).1Some MDCs are involved in (patho-) physiological relevant processes such as remodelling of the extracellular matrix as well as shedding of membrane-bound cytokines (e.g. TNF-alpha).2,3 An implication of MDC15 in degenerative processes of the cartilage matrix is supported by a markedly strong up-regulated expression of this proteinase in the chondrocytes of arthritic cartilage4

Objectives In the present study the expression of MDC15 in synovial membranes of patients with Rheumatoid Arthritis (RA) in comparison to osteoarthritic (OA) and normal specimens was analysed.

Methods Using in situ hybridization the expression of MDC15 mRNA was investigated in RA synovial tissues of synovectomy samples (n = 25), in OA tissues (n = 55) that was obtained at joint replacement surgery of hip or knee joints and normal synovial tissues (n = 8). On protein level the detection of MDC15 was performed by immunohistochemistry. A specific polyclonal antibody was generated in rabbits by immunisation with a synthetic cyclized peptide corresponding to the disintegrin domain. After affinity chromatographic purification specificity of the antibody was confirmed by Western blot analysis using COS-7 cells transfected with the full-length MDC15 cDNA.

Results By in situ hybridization as well as by immunohistochemistry highest expression of MDC15 could be detected in the synovial lining cells in all RA synovial tissues analysed. In comparison to the RA specimens, far lower levels of expression were observed in the synoviocytes of OA specimens that still exceeded the very low expression found in normal synovial tissues.

Conclusion The enhanced expression of MDC15 in the rheumatoid synovial lining layer suggests a potential role in the pathophysiology of cartilage destruction, since the membrane-bound proteinase might be of relevance in the activation of matrix metalloproteinases and/or also be involved in the direct proteolytic degradation of extracellular matrix molecules.

References

  1. Primakoff P, Myles DG. Trends Genet. 2000;16:83–7

  2. Chubinskaya S, Cs-Szabo G, Kuettner KE. J Histochem Cytochem. 1998;46:723–30

  3. Patel IR, Attur MG, Patel RN, Stuchin SA, Abagyan RA, Abramson SB, Amin AR. J Immunol. 1998;160:4570–79

  4. Böhm BB, Aigner T, Gehrsitz A, Blobel CP, Kalden JR, Burkhardt H. Arthritis Rheum. 1999;42:1946–50

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