| Objective: The study aimed to elucidate the formation process and therapeutic strategies of knee extension contracture,we developed a rat model using an aluminum external fixator.Methods: Sixty male Sprague-Dawley rats with mature bones were divided into the control group(n=6)and groups that had the left knee immobilized with an aluminum external fixator for 1,2,and 3 days,and 1,2,3,4,6,and 8 weeks(n=6 in each group).The passive extension range of motion,histology,and expression of fibrosis-related proteins were compared between the control group and the immobilization groups.Results: Myogenic contracture progressed very quickly during the initial 2 weeks of immobilization;after 2 weeks,the contracture gradually changed from myogenic to arthrogenic.The arthrogenic contracture progressed slowly during the first week,rapidly progressed until the third week,and then showed a steady progression.Histological analysis confirmed that the anterior joint capsule of the extended fixed knee became increasingly thicker over time.Correspondingly,the level of TGF-β1 and p-Smad2 in the anterior joint capsule also increased with the immobilization time.Over time,the cross-sectional area of muscle fibers gradually decreased,while the amount of intermuscular collagen and TGF-β1,p-Smad2 and p-Smad3 increased.Unexpectedly,the amount of intermuscular collagen and TGF-β1,p-Smad2 and p-Smad3 decreased during the late stage of immobilization(6-8 weeks).Conclusion: Myogenic contracture is stabilized after 2 weeks of immobilization,while arthrogenic contracture tends to stabilize after 3 weeks and has stabilized after 4 weeks.This rat model may be a useful tool to study the etiology of joint contracture and establish therapeutic approaches. |