title: Human granzyme B mediates cartilage proteoglycan degradation and is expressed at the invasive front of the synovium in rheumatoid arthritis.
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 [(3)H]proline/[(35)S]sulphate-labelled cartilage matrices and to cartilage explants. Proteoglycan degradation was assessed by the release of (35)S and glycosaminoglycans into the medium and collagen degradation was assessed by the release of (3)H 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands.
authors.forename: H K
authors.initials: HK
authors.lastname: Ronday
authors.forename: W H
authors.initials: WH
authors.lastname: van der Laan
authors.forename: P P
authors.initials: PP
authors.lastname: Tak
authors.forename: J A
authors.initials: JA
authors.lastname: de Roos
authors.forename: R A
authors.initials: RA
authors.lastname: Bank
authors.forename: J M
authors.initials: JM
authors.lastname: TeKoppele
authors.forename: C J
authors.initials: CJ
authors.lastname: Froelich
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.forename: P C
authors.initials: PC
authors.lastname: Hogendoorn
authors.forename: F C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: J H
authors.initials: JH
authors.lastname: Verheijen
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002356:Cartilage / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D053804:Granzymes; D006801:Humans; D008662:Metacarpophalangeal Joint / Q000201:enzymology; D011509:Proteoglycans / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D013583:Synovial Membrane / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology
chemical_list: D011509:Proteoglycans; D003094:Collagen; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases