The mast cell stabilizer ketotifen reduces joint capsule fibrosis in a rabbit model of post-traumatic joint contractures

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. 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 alpha-SMA, tryptase, TGF-beta 1, collagen I and collagen III. Significance was tested using an ANOVA analysis of variance. The protein and mRNA levels of alpha-SMA, TGF-beta 1, 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 alpha-SMA, TGF-beta 1 and collagen I were significantly reduced compared to the operated contracture group (p < 0.01). These data suggest an inflammatory pathway mediated by mast cell activation is involved in joint capsule fibrosis after traumatic injury.