title: Extracellular superoxide dismutase and oxidant damage in osteoarthritis.
abstract: OBJECTIVE
  To use human cartilage samples and a mouse model of osteoarthritis (OA) to determine whether extracellular superoxide dismutase (EC-SOD) is a constituent of cartilage and to evaluate whether there is a relationship between EC-SOD deficiency and OA.
  
  
  METHODS
  Samples of human cartilage were obtained from femoral heads at the time of joint replacement surgery for OA or femoral neck fracture. Samples of mouse tibial cartilage obtained from STR/ort mice and CBA control mice were compared at 5, 15, and 35 weeks of age. EC-SOD was measured by enzyme-linked immunosorbent assay, Western blotting, and immunohistochemistry techniques. Real-time quantitative reverse transcription-polymerase chain reaction was used to measure messenger RNA for EC-SOD and for endothelial cell, neuronal, and inducible nitric oxide synthases. Nitrotyrosine formation was assayed by Western blotting in mouse cartilage and by fluorescence immunohistochemistry in human cartilage.
  
  
  RESULTS
  Human articular cartilage contained large amounts of EC-SOD (mean +/- SEM 18.8 +/- 3.8 ng/gm wet weight of cartilage). Cartilage from patients with OA had an approximately 4-fold lower level of EC-SOD compared with cartilage from patients with hip fracture. Young STR/ort mice had decreased levels of EC-SOD in tibial cartilage before histologic evidence of disease occurred, as well as significantly more nitrotyrosine formation at all ages studied.
  
  
  CONCLUSIONS
  EC-SOD, the major scavenger of reactive oxygen species in extracellular spaces, is decreased in humans with OA and in an animal model of OA. Our findings suggest that inadequate control of reactive oxygen species plays a role in the pathophysiology of OA.
authors.affiliation: Department of Medicine, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA. regane@njc.org
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Regan
authors.forename: Joanne
authors.initials: J
authors.lastname: Flannelly
authors.forename: Russell
authors.initials: R
authors.lastname: Bowler
authors.forename: Karen
authors.initials: K
authors.lastname: Tran
authors.forename: Michael
authors.initials: M
authors.lastname: Nicks
authors.forename: Beth Duda
authors.initials: BD
authors.lastname: Carbone
authors.forename: Deborah
authors.initials: D
authors.lastname: Glueck
authors.forename: Harry
authors.initials: H
authors.lastname: Heijnen
authors.forename: Roger
authors.initials: R
authors.lastname: Mason
authors.forename: James
authors.initials: J
authors.lastname: Crapo
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002358:Cartilage, Articular / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005270:Femur Head; D016166:Free Radical Scavengers / Q000378:metabolism*; D006614:Hindlimb; D006801:Humans; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D015207:Osteoarthritis, Hip / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013977:Tibia; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; C441642:SOD3 protein, human; D013482:Superoxide Dismutase