The mast cell stabilizer ketotifen reduces joint capsule fibrosis in a rabbit model of post-traumatic joint contractures
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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 α-SMA, tryptase, TGF-β1, collagen I and collagen III. Significance was tested using an ANOVA analysis of variance.
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).
These data suggest an inflammatory pathway mediated by mast cell activation is involved in joint capsule fibrosis after traumatic injury.
KeywordsKetotifen Mast cells Fibrosis Rabbit Post-traumatic
We would like to thank the Canadian Orthopaedic Foundation for their generous funding of this project via the Robert Salter Award. D.A.H. is the Calgary Foundation–Grace Glaum Professor. All authors have no financial affiliations to disclose regarding this research.