Title
Human granzyme B mediates cartilage proteoglycan degradation and is expressed at the invasive front of the synovium in rheumatoid arthritis
Author
Ronday, H.K.
van der Laan, W.H.
Tak, P.P.
de Roos, J.A.D.M.
Bank, R.A.
Tekoppele, J.M.
Froelich, C.J.
Hack, C.E.
Hogendoorn, P.C.W.
Breedveld, F.C.
Verheijen, J.H.
Gaubius Instituut
Publication year
2001
Abstract
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.
Subject
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
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http://resolver.tudelft.nl/uuid:76072712-13cf-479d-9980-495ce1c16d5f
TNO identifier
235982
ISSN
1462-0324
Source
Rheumatology, 40 (1), 55-61
Document type
article