title: Resistin is elevated following traumatic joint injury and causes matrix degradation and release of inflammatory cytokines from articular cartilage in vitro.
abstract: OBJECTIVE
  Resistin is a secreted factor that is elevated in rheumatoid arthritis (RA) and believed to drive joint inflammation in vivo. This study was undertaken to determine if resistin is present in the joint following joint injury and to elucidate the role of resistin in cartilage degradation.
  
  
  METHODS
  The level of resistin was measured in paired synovial fluid (SF) and serum samples from patients following joint injury (anterior cruciate ligament, ACL or meniscus tear). Localization of resistin was visualized by immunohistochemistry of synovial tissue and cartilage from healthy and OA donors. Mouse and human cartilage cultures were used to assess the effect of resistin on cartilage metabolism.
  
  
  RESULTS
  In trauma patients, resistin levels declined with increasing time post injury. The resistin levels were highest in samples collected up to 1 week following traumatic injury (SF: 2980 pg/ml, serum: 7901 pg/ml) and lowest in samples collected 6-26 years post injury (SF: 686 pg/ml, serum: 5682 pg/ml). Resistin was shown to be expressed in macrophage-like cells in both healthy and OA synovial tissue. Treatment of mouse cartilage cultures with recombinant resistin led to a dose dependent loss of proteoglycan and induction of inflammatory cytokine and PGE(2) production. Recombinant resistin inhibited proteoglycan synthesis in human cartilage explants.
  
  
  CONCLUSIONS
  Resistin is elevated both systemically and locally in the weeks immediately following joint injury and has a direct effect on cartilage matrix turnover and cytokine production. Resistin may play a role in the early stages of trauma-induced OA and may represent a new therapeutic target to slow joint destruction in OA.
authors.affiliation: Discovery Research, Centocor Research & Development, Radnor, PA 19087, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: T
authors.initials: T
authors.lastname: Ort
authors.forename: K
authors.initials: K
authors.lastname: Ma
authors.forename: K
authors.initials: K
authors.lastname: Picha
authors.forename: J
authors.initials: J
authors.lastname: Carton
authors.forename: P A
authors.initials: PA
authors.lastname: Marsters
authors.forename: L S
authors.initials: LS
authors.lastname: Lohmander
authors.forename: F
authors.initials: F
authors.lastname: Baribaud
authors.forename: X-Y R
authors.initials: XY
authors.lastname: Song
authors.forename: S
authors.initials: S
authors.lastname: Blake
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002358:Cartilage, Articular / Q000293:injuries / Q000378:metabolism*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007596:Joints / Q000293:injuries / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D052243:Resistin / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018836:Inflammation Mediators; D052243:Resistin