title: Early structural changes in cartilage and bone are required for the attachment and invasion of inflamed synovial tissue during destructive inflammatory arthritis.
abstract: OBJECTIVE
  To elucidate the mechanisms involved in cartilage damage in an experimental model of rheumatoid arthritis (RA) by specifically addressing the time course of extracellular matrix degradation and the contribution of cell-matrix interactions for initiation and perpetuation of this process.
  
  
  METHODS
  The human tumour necrosis factor (TNF) transgenic (hTNFtg) mouse model of RA was used to analyse the time course of pannus attachment to the cartilage and cartilage destruction, respectively, and crossed hTNFtg mice with interleukin (IL)-1(-/-) animals were used to investigate the role of IL-1 on these TNF-induced mechanisms in vivo. In addition, an in vitro attachment assay using synovial fibroblasts (SFs) from hTNFtg mice and freshly isolated articular cartilage was used to determine the role of proteoglycan loss in attachment of SFs and the role of the transmembrane heparan sulfate proteoglycan syndecan-4.
  
  
  RESULTS
  In vivo analyses of hTNFtg mice showed that proteoglycan loss induced by IL-1 precedes and constitutes an important prerequisite for these processes as, in hTNFtg mice, IL-1 deficiency protected from the loss of cartilage proteoglycans and almost completely prevented the attachment and subsequent invasion of inflamed synovial tissue into cartilage. In vitro studies confirmed that loss of cartilage proteoglycans is required for attachment of SFs and that syndecan-4 is prominently involved in SF attachment and activation.
  
  
  CONCLUSIONS
  The results of this study suggest that the loss of cartilage proteoglycans is an early event in the course of destructive arthritis that facilitates the attachment of the inflamed synovial membrane and also initiates matrix degradation and inflammation through cell-matrix interactions.
authors.affiliation: Division of Rheumatology, Medical University Vienna, Vienna, Austria.
authors.forename: Adelheid
authors.initials: A
authors.lastname: Korb-Pap
authors.forename: Athanasios
authors.initials: A
authors.lastname: Stratis
authors.forename: Katja
authors.initials: K
authors.lastname: Mühlenberg
authors.forename: Birgit
authors.initials: B
authors.lastname: Niederreiter
authors.forename: Silvia
authors.initials: S
authors.lastname: Hayer
authors.forename: Frank
authors.initials: F
authors.lastname: Echtermeyer
authors.forename: Richard
authors.initials: R
authors.lastname: Stange
authors.forename: Jochen
authors.initials: J
authors.lastname: Zwerina
authors.forename: Thomas
authors.initials: T
authors.lastname: Pap
authors.forename: Hermann
authors.initials: H
authors.lastname: Pavenstädt
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.forename: Kurt
authors.initials: K
authors.lastname: Redlich
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001842:Bone and Bones / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002356:Cartilage / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000276:immunology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011509:Proteoglycans / Q000378:metabolism; D053671:Syndecan-4 / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D013585:Synovitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D007375:Interleukin-1; D011509:Proteoglycans; C508306:Sdc4 protein, mouse; D053671:Syndecan-4; D014409:Tumor Necrosis Factor-alpha