title: The mast cell stabilizer ketotifen reduces joint capsule fibrosis in a rabbit model of post-traumatic joint contractures.
abstract: OBJECTIVE
  Using a rabbit model of post-traumatic joint contractures, we investigated whether treatment with a mast cell stabilizer after joint injury would lessen the molecular manifestations of joint capsule fibrosis.
  
  
  METHODS
  Surgical joint injury was used to create stable post-traumatic contractures of the knee in skeletally mature New Zealand white rabbits. Four groups of animals were studied: a non-operated control group (n = 8), an operated contracture group (n = 13) and two operated groups treated with the mast cell stabilizer, ketotifen, at doses of 0.5 mg/kg (n = 9) and 1.0 mg/kg (n = 9) twice daily. Joint capsule fibrosis was assessed by quantifying the mRNA and protein levels of α-SMA, tryptase, TGF-β1, collagen I and collagen III. Significance was tested using an ANOVA analysis of variance.
  
  
  RESULTS
  The protein and mRNA levels of α-SMA, TGF-β1, tryptase and collagen I and III were significantly elevated in the operated contracture group compared to control (p < 0.01). In both ketotifen-treated groups, protein and mRNA levels of α-SMA, TGF-β1 and collagen I were significantly reduced compared to the operated contracture group (p < 0.01).
  
  
  CONCLUSIONS
  These data suggest an inflammatory pathway mediated by mast cell activation is involved in joint capsule fibrosis after traumatic injury.
authors.affiliation: Division of Orthopaedic Surgery, Faculty of Medicine, McCaig Institute for Bone and Joint Health, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada. mjmonume@ucalgary.ca
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Monument
authors.forename: David A
authors.initials: DA
authors.lastname: Hart
authors.forename: A Dean
authors.initials: AD
authors.lastname: Befus
authors.forename: Paul T
authors.initials: PT
authors.lastname: Salo
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Hildebrand
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D003286:Contracture / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D017746:Joint Capsule / Q000187:drug effects / Q000473:pathology; D007665:Ketotifen / Q000627:therapeutic use*; D008407:Mast Cells; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D053802:Tryptases / Q000235:genetics
chemical_list: D000199:Actins; D018926:Anti-Allergic Agents; D024042:Collagen Type I; D024061:Collagen Type III; D006634:Histamine H1 Antagonists; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D053802:Tryptases; D007665:Ketotifen