title: Free radical damage in facsimile synovium: correlation with adhesion formation in osteoarthritic TMJs.
abstract: OBJECTIVE
  The purpose of this study was to use the rat air pouch model of facsimile synovium to evaluate oxidative stress as a primary mechanism in the pathogenesis of degenerative temporomandibular joint (TMJ) disease.
  
  
  METHODS
  Forty-nine Sprague-Dawley adult female rats were used to generate the standard rat air pouch model of facsimile synovium. This was accomplished by daily air injections (20 cc) subdermally through the dorsal skin. Hydrogen peroxide and ferrous iron (components of the Fenton reaction which generate free radicals) were introduced into the pouches of the 4-, 7-, and 14-day groups to generate oxidative stress. Control rats were injected with phosphate-buffered solution (PBS), pH 7.4. Either N-acetylcysteine (NAC), a powerful free radical scavenger, or ibuprofen were simultaneously injected with the Fenton reagents into the pouches of the 14-day treatment groups to modulate free radical-mediated protein damage to the synovium. Animals were euthanized at appropriate experimental intervals and biopsies obtained from specimens to analyze: (1) proteins' amino acid modification (carbonyl group formation), (2) protein hydrophobicity, (3) detection of low molecular weight protein degradation products, and (4) histological and gross anatomical observations.
  
  
  RESULTS
  Free radicals introduced into the rat air pouch interacted with synovial tissues causing oxidation and breakdown of proteins. Clinical evidence of adhesion formation consistent with features found in osteoarthritis of the TMJ developed. The groups subjected to oxidative stress experienced statistically significant (p < 0.05) increases in carbonyl formation, carbonyls/protein, and low molecular weight protein fragments. These groups also showed significant (p < 0.05) hydrophobicity changes consistent with free radical attack. Control synovial tissues were statistically undamaged. The 14-day NAC and ibuprofen treatment groups experienced statistically significant (p < 0.05) decreases in total carbonyl formation, carbonyls/protein, and hydrophobicity. Histological and gross observations in free radical damaged synovium exhibited features consistent with known arthoscopic and arthrocentesis findings in diseased TMJs.
  
  
  CONCLUSIONS
  This study suggests that the rat air pouch model of facsimile synovium develops clinical evidence of adhesions and biochemical signs of protein modification when subjected to free radical attack. NAC and ibuprofen prevented carbonyl formation as well as hydrophobicity changes indicative of oxidative stress damage in facsimile synovium. These findings are consistent with features of degenerative human TMJ disease. Future direction may be taken from this study to postulate new analysis techniques and treatment modalities for patients with degenerative TMJ disease.
authors.affiliation: Department of Prosthodontics, Wilford Hall Medical Center, Lackland AFB, San Antonio, TX, USA.
authors.forename: Donald W
authors.initials: DW
authors.lastname: Sheets
authors.forename: Toru
authors.initials: T
authors.lastname: Okamoto
authors.forename: Leonore C
authors.initials: LC
authors.lastname: Dijkgraaf
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Milam
authors.forename: John P
authors.initials: JP
authors.lastname: Schmitz
authors.forename: Gustavo
authors.initials: G
authors.lastname: Zardeneta
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005609:Free Radicals / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000008:administration & dosage; D057927:Hydrophobic and Hydrophilic Interactions; D007279:Injections, Subcutaneous; D007501:Iron / Q000008:administration & dosage; D010003:Osteoarthritis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D050050:Protein Carbonylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000473:pathology*; D013705:Temporomandibular Joint Disorders / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000267:Tissue Adhesions / Q000209:etiology
chemical_list: C045076:Fenton's reagent; D005609:Free Radicals; D006861:Hydrogen Peroxide; D007501:Iron