title: Xanthine oxidase injurious response in acute joint injury.
abstract: BACKGROUND
  While acute trauma is a major cause of osteoarthritis, its etiology is poorly understood. We sought to determine whether xanthine oxidase (XO), a major producer of reactive oxygen species, plays a role in the early events of acute joint injury.
  
  
  METHODS
  We analyzed synovial fluid from 23 subjects with recent severe acute knee injury. As a control we evaluated SF from 23 individuals with no or minimal knee osteoarthritis. We measured XO activity, reactive oxygen+reactive nitrogen species (ROS+RNS), protein oxidative damage (carbonyl), the type II collagen synthesis marker procollagen II c-propeptide (CPII) and the type II collagen degradation marker collagen type II telopeptide (CTx-II). We also measured the proinflammatory cytokine IL-6.
  
  
  RESULTS
  XO and ROS+RNS were higher (p=0.02 and p=0.001 respectively) in acute injury than control and were strongly positively associated (r=0.62, p=0.004). Carbonyl was higher in acute injury than control (p=0.0002) and was positively correlated with XO (r=0.68, p=0.0007) as well as with ROS+RNS (r=0.71, p=0.004). CPII was higher in acute injury than control (p<0.0001) and was negatively correlated with XO (r=-0.49, p=0.017). While CTxII was not significantly higher in acute injury than control, it was positively correlated with CPII (r=0.71, p=0.0002). IL-6 was higher in acute injury than control (p<0.0001).
  
  
  CONCLUSIONS
  These results are consistent with a potentially injurious effect of XO activity in acute joint injury characterized by excess free radical production and oxidative damage. These effects are associated with an inhibition of type II collagen production that may impede the ability of the injured joint to repair.
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA. Electronic address: tvs@duke.edu.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stabler
authors.affiliation: Department of Orthopaedic Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Zura
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Hsueh
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA; Department of Medicine, Division of Rheumatology, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Virginia B
authors.initials: VB
authors.lastname: Kraus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024043:Collagen Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*; D055815:Young Adult
chemical_list: D024043:Collagen Type II; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D014969:Xanthine Oxidase
keywords: Knee injury; Osteoarthritis; Oxidation; Xanthine oxidase