Anti-fibrotic effects of the antihistamine ketotifen in a rabbit model of arthrofibrosis

Bone & Joint Research

article

Meagan E Tibbo¹  Afton K Limberg¹  Christopher G Salib¹  Travis W Turner¹  Alex R McLaury¹  Anthony G Jay¹  Jacob W Bettencourt¹  Jodi M Carter¹  Brad Bolon²  Daniel J Berry¹  Mark E Morrey¹  Joaquin Sanchez-Sotelo¹  Andre J van Wijnen³  Matthew P Abdel¹ 

[1] Department of Orthopedic Surgery, Mayo Clinic;GEMpath, Inc.;Department of Orthopedic Surgery and Department of Biochemistry & Molecular Biology, Mayo Clinic

关键词: Acquired idiopathic stiffness;    Arthrofibrosis;    Ketotifen;    Myofibroblast;    Total knee arthroplasty;    Joint fibrosis;   

DOI  :  10.1302/2046-3758.96.BJR-2019-0272.R2

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

AimsArthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits.MethodsA group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein).ResultsAt the 24-week timepoint, there was a statistically significant increase in passive extension among rabbits treated with ketotifen compared to those treated with saline (p = 0.03). However, no difference in capsular stiffness was detected. Histopathological data failed to demonstrate a decrease in the density of fibrous tissue or a decrease in α-smooth muscle actin (α-SMA) staining with ketotifen treatment. In contrast, tryptase and α-SMA protein expression in the ketotifen group were decreased when compared to saline controls (p = 0.007 and p = 0.01, respectively). Furthermore, there was a significant decrease in α-SMA (ACTA2) gene expression in the ketotifen group compared to the control group (p < 0.001).ConclusionCollectively, these data suggest that ketotifen mitigates the severity of contracture formation in a rabbit model of arthrofibrosis.

【 授权许可】

CC BY-NC