title: Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage.
abstract: BACKGROUND
  Tenascin-C (TN-C) is an extracellular matrix glycoprotein that is involved in tissue injury and repair processes. We analyzed TN-C expression in normal and osteoarthritic (OA) human cartilage, and evaluated its capacity to induce inflammatory and catabolic mediators in chondrocytes in vitro. The effect of TN-C on proteoglycan loss from articular cartilage in culture was also assessed.
  
  
  METHODS
  TN-C in culture media, cartilage extracts, and synovial fluid of human and animal joints was quantified using a sandwich ELISA and/or analyzed by Western immunoblotting. mRNA expression of TN-C and aggrecanases were analyzed by Taqman assays. Human and bovine primary chondrocytes and/or explant culture systems were utilized to study TN-C induced inflammatory or catabolic mediators and proteoglycan loss. Total proteoglycan and aggrecanase -generated ARG-aggrecan fragments were quantified in human and rat synovial fluids by ELISA.
  
  
  RESULTS
  TN-C protein and mRNA expression were significantly upregulated in OA cartilage with a concomitant elevation of TN-C levels in the synovial fluid of OA patients. IL-1 enhanced TN-C expression in articular cartilage. Addition of TN-C induced IL-6, PGE2, and nitrate release and upregulated ADAMTS4 mRNA in cultured primary human and bovine chondrocytes. TN-C treatment resulted in an increased loss of proteoglycan from cartilage explants in culture. A correlation was observed between TN-C and aggrecanase generated ARG-aggrecan fragment levels in the synovial fluid of human OA joints and in the lavage of rat joints that underwent surgical induction of OA.
  
  
  CONCLUSIONS
  TN-C expression in the knee cartilage and TN-C levels measured in the synovial fluid are significantly enhanced in OA patients. Our findings suggest that the elevated levels of TN-C could induce inflammatory mediators and promote matrix degradation in OA joints.
authors.affiliation: Tissue Repair, BioTherapeutics Research & Development, Pfizer, Cambridge, MA, USA.
authors.forename: Lisha
authors.initials: L
authors.lastname: Patel
authors.forename: Weiyong
authors.initials: W
authors.lastname: Sun
authors.forename: Sonya S
authors.initials: SS
authors.lastname: Glasson
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Morris
authors.forename: Carl R
authors.initials: CR
authors.lastname: Flannery
authors.forename: Priya S
authors.initials: PS
authors.lastname: Chockalingam
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D013582:Synovial Fluid / Q000378:metabolism; D019063:Tenascin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018836:Inflammation Mediators; D019063:Tenascin