title: Joint fluid antioxidants are decreased in osteoarthritic joints compared to joints with macroscopically intact cartilage and subacute injury.
abstract: OBJECTIVE
  Excess reactive oxygen species and oxidative damage have been associated with the pathogenesis of osteoarthritis (OA). Extracellular superoxide dismutase (EC-SOD or SOD3) scavenges superoxide is the major catalytic antioxidant in joint fluid and is decreased in OA cartilage. We studied human joint fluid samples to test whether there is an association between OA and EC-SOD or other low molecular antioxidants in the joint fluid.
  
  
  METHODS
  Joint fluid samples were obtained from 28 subjects with severe OA undergoing arthrocentesis or knee joint replacement and compared to joint fluid from 12 subjects undergoing knee arthroscopy for chronic knee pain, meniscal tears or anterior cruciate ligament reconstruction. EC-SOD protein was assayed by enzyme-linked immunosorbent assay (ELISA). Ascorbate and urate were measured with high performance liquid chromatography (HPLC) and total nitrates by the Greiss reaction. Glutathione (GSH) and oxidized glutathione were measured using a colorimetric method. Interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) were both measured with ELISA.
  
  
  RESULTS
  Human joint fluid contains significant amounts of the extracellular, catalytic antioxidant EC-SOD. Joint fluid from OA subjects is characterized by significantly decreased EC-SOD levels and significant decreases in GSH, and ascorbate compared to the reference group of knee joints with pain or subacute injury but macroscopically intact cartilage. GSH and ascorbate show only an age effect with no effect from disease state on regression modeling. Urate is present in joint fluid but does not show a significant difference between groups. IL-6 and TGF-beta both show non-significant trends to increases in the arthritic subjects. There was no correlation of EC-SOD levels with IL-6 as a marker of inflammation in either the comparison group or the OA group.
  
  
  CONCLUSIONS
  EC-SOD, the major scavenger of reactive oxygen species (ROS) in extracellular spaces and fluids, is decreased in late stage OA joint fluid compared to fluid from injured/painful joints with intact cartilage. Injured joints may be able to increase or maintain secretion of EC-SOD but it appears that late stage OA joints fail to do so in spite of increased oxidative stress seen in the disease. Associated age related declines in GSH and ascorbate might also contribute to the development of severe OA. The net effect of these changes in joint fluid antioxidants is likely to accelerate the damaging oxidant effects on extracellular matrix stability in cartilage tissue.
authors.affiliation: Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, United States. regane@njc.org
authors.forename: E A
authors.initials: EA
authors.lastname: Regan
authors.forename: R P
authors.initials: RP
authors.lastname: Bowler
authors.forename: J D
authors.initials: JD
authors.lastname: Crapo
mesh_terms: D000367:Age Factors; D002358:Cartilage, Articular / Q000378:metabolism* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism* / Q000494:pharmacology; D005978:Glutathione; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007719:Knee Joint / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009566:Nitrates; D009573:Nitrites; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000503:physiopathology; D010146:Pain; D017382:Reactive Oxygen Species / Q000009:adverse effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism* / Q000494:pharmacology; D013582:Synovial Fluid / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014527:Uric Acid / Q000032:analysis
chemical_list: D016166:Free Radical Scavengers; D015850:Interleukin-6; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D014527:Uric Acid; C441642:SOD3 protein, human; D013482:Superoxide Dismutase; D005978:Glutathione