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Human granzyme B mediates cartilage proteoglycan degradation and is expressed at the invasive front of the synovium in rheumatoid arthritis

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Author: Ronday, H.K. · Laan, W.H. van der · Tak, P.P. · Roos, J.A.D.M. de · Bank, R.A. · Tekoppele, J.M. · Froelich, C.J. · Hack, C.E. · Hogendoorn, P.C.W. · Breedveld, F.C. · Verheijen, J.H.
Institution: Gaubius Instituut
Source:Rheumatology, 1, 40, 55-61
Identifier: 235982
Keywords: Biology Health · Biomedical Research · Cartilage destruction · Granzyme B · Rheumatoid arthritis · collagen · glycosaminoglycan · granzyme B · hydroxyproline · proline · proteoglycan · sulfate · sulfur 35 · tritium · animal tissue · bone erosion · cartilage degeneration · cartilage matrix · collagen degradation · controlled study · explant · human cell · immunohistochemistry · isotope labeling · joint destruction · nonhuman · priority journal · protein denaturation · protein expression · proteoglycan synthesis · rheumatoid arthritis · synovium · Animals · Arthritis, Rheumatoid · Cartilage · Cattle · Cells, Cultured · Chondrocytes · Collagen · Extracellular Matrix · Granzymes · Humans · Metacarpophalangeal Joint · Proteoglycans · Serine Endopeptidases · Synovial Membrane


Objective. To investigate the cartilage-degrading capacity of granzyme B and the presence of granzyme B-positive cells at sites of erosion in the rheumatoid synovium. Methods. Granzyme B was added to [3H]proline/[35S]sulphate-labelled cartilage matrices and to cartilage explants. Proteoglycan degradation was assessed by the release of 35S and glycosaminoglycans into the medium and collagen degradation was assessed by the release of 3H and hydroxyproline and by measuring the fraction of denatured collagen. Granzyme B expression was studied at the invasive front of the synovium by immunohistochemistry. Results. Granzyme B induced loss of both newly synthesized, radiolabelled proteoglycans in cartilage matrices and resident proteoglycans of the cartilage explants. No effect on collagen degradation was found. Granzyme B-positive cells were present throughout the synovium and at the invasive front. Conclusion. The presence of granzyme B-positive cells at the invasive front of the synovium together with its ability to degrade articular proteoglycans supports the view that granzyme B may contribute to joint destruction in rheumatoid arthritis.