title: Profiling the secretion of soluble mediators by end stage osteoarthritis synovial tissue explants reveals a reduced responsiveness to an inflammatory trigger.
abstract: OBJECTIVE
  Evidence is accumulating that synovial tissue plays an active role in osteoarthritis (OA), however, exact understanding of its contribution is lacking. In order to further elucidate its role in the OA process, we aimed to identify the secretion pattern of soluble mediators by synovial tissue and to assess its ability to initiate cartilage degeneration.
  
  
  METHODS
  Synovial tissue explants (STEs) obtained from donors without history of OA (n = 8) or from end stage OA patients (n = 16) were cultured alone or together with bovine cartilage explants in the absence or presence of IL-1α. The secretion of 48 soluble mediators was measured and the effect on glycosaminoglycan (GAG) release and matrix metalloproteinase (MMP) activity was determined.
  
  
  RESULTS
  Normal and OA STEs secreted comparable levels of almost all measured soluble mediators. However, in the presence of IL-1α these mediators were less secreted by OA than by normal STEs of which 15 differed significantly (p<0.01). No effect of normal or OA STEs on GAG release from the cartilage explants was observed, and no differences in MMP activity between OA and normal STEs were detected.
  
  
  CONCLUSIONS
  Unexpectedly, a comparable secretion profile of soluble mediators was found for OA and normal STEs while the reduced responsiveness of OA STEs to an inflammatory trigger indicates a different state of this tissue in OA patients. The effects could be the result of prolonged exposure to an inflammatory environment in OA development. Further understanding of the pro-inflammatory and inflammation resolving mechanisms during disease progression in synovial tissue may provide valuable targets for therapy in the future.
authors: TNO, Leiden, The Netherlands.
authors: Lobke M
authors: LM
authors: Gierman
authors: Benno
authors: B
authors: van El
authors: Frits
authors: F
authors: van der Ham
authors: Angela
authors: A
authors: Koudijs
authors: Reinout
authors: R
authors: Stoop
authors: Jan H
authors: JH
authors: Verheijen
authors: Margreet
authors: M
authors: Kloppenburg
authors: Gerjo J V M
authors: GJ
authors: van Osch
authors: Vedrana
authors: V
authors: Stojanovic-Susulic
authors: Tom W J
authors: TW
authors: Huizinga
authors: Anne-Marie
authors: AM
authors: Zuurmond
mesh_terms: D000293:Adolescent; D000368:Aged; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002417:Cattle; D006025:Glycosaminoglycans / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007249:Inflammation; D018836:Inflammation Mediators / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000494:pharmacology; D017746:Joint Capsule / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism*; D046509:Tissue Culture Techniques
chemical_list: D006025:Glycosaminoglycans; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D020782:Matrix Metalloproteinases
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