title: Tenascin-C levels in synovial fluid are elevated after injury to the human and canine joint and correlate with markers of inflammation and matrix degradation.
abstract: OBJECTIVE
  We have previously shown the capacity of tenascin-C (TN-C) to induce inflammatory mediators and matrix degradation in vitro in human articular cartilage. The objective of the present study was to follow TN-C release into knee synovial fluid after acute joint injury or in joint disease, and to correlate TN-C levels with markers of cartilage matrix degradation and inflammation.
  
  
  METHODS
  Human knee synovial fluid samples (n = 164) were from a cross-sectional convenience cohort. Diagnostic groups were knee healthy reference, knee anterior cruciate ligament rupture, with or without concomitant meniscus lesions, isolated knee meniscus injury, acute inflammatory arthritis (AIA) and knee osteoarthritis (OA). TN-C was measured in synovial fluid samples using an enzyme-linked immunosorbent assay (ELISA) and results correlated to other cartilage markers. TN-C release was also monitored in joints of dogs that underwent knee instability surgery.
  
  
  RESULTS
  Statistically significantly higher levels of TN-C compared to reference subjects were observed in the joint fluid of all human disease groups and in the dogs that underwent knee instability surgery. Statistically significant correlations were observed between the TN-C levels in the synovial fluid of the human patients and the levels of aggrecanase-dependent Ala-Arg-Gly-aggrecan (ARG-aggrecan) fragments and matrix metalloproteinases 1 and 3.
  
  
  CONCLUSIONS
  We find highly elevated levels of TN-C in human knee joints after injury, AIA or OA that correlated with markers of cartilage degradation and inflammation. TN-C in synovial fluid may serve dual roles as a marker of joint damage and a stimulant of further joint degradation.
authors.affiliation: Inflammation and Remodelling, Pfizer, Cambridge, MA, USA. priya.chockalingam@pfizer.com
authors.forename: P S
authors.initials: PS
authors.lastname: Chockalingam
authors.forename: S S
authors.initials: SS
authors.lastname: Glasson
authors.forename: L S
authors.initials: LS
authors.lastname: Lohmander
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D001168:Arthritis / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006801:Humans; D007592:Joint Diseases / Q000378:metabolism*; D007718:Knee Injuries / Q000378:metabolism*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism*; D019063:Tenascin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D053674:Aggrecans; D015415:Biomarkers; D019063:Tenascin; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1