Development of a novel knee contracture mouse model by immobilization using external fixation

Several studies have used animal models to examine knee joint contracture; however, few reports detail the construction process of a knee joint contracture model in a mouse. The use of mouse models is beneficial, as genetically modified mice can be used to investigate the pathogenesis of joint contracture. Compared to others, mouse models are associated with a lower cost to evaluate therapeutic effects. Here, we describe a novel knee contracture mouse model by immobilization using external fixation. The knee joints of mice were immobilized by external fixation using a splint and tape. The passive extension range of motion (ROM), histological and immunohistochemical changes, and expression levels of fibrosis-related genes at 2 and 4 weeks were compared between the immobilized (Im group) and non-immobilized (Non-Im group) groups. The extension ROM at 4 weeks was significantly lower in the Im group than in the Non-Im group (p transforming growth factor-β1, and the protein levels of cellular communication network factor 2 and vimentin in the joint capsule were significantly higher in the Im group (p This mouse model may serve as a useful tool to investigate the etiology of joint contracture and establish new treatment methods.已有多项研究借助动物模型探究膝关节挛缩，但鲜有文献详述小鼠膝关节挛缩模型的构建流程。使用小鼠模型具备显著优势：可通过转基因小鼠（genetically modified mice）探究关节挛缩的发病机制；相较于其他动物模型，小鼠模型在评估治疗效果时成本更低。本文介绍一种新型外固定制动式膝关节挛缩小鼠模型：通过夹板与胶带实施外固定以制动小鼠膝关节。分别于制动后2周与4周，对比制动组（Im组）与非制动组（Non-Im组）小鼠的被动伸展活动度（ROM）、组织学与免疫组织化学变化，以及纤维化相关基因的表达水平。结果显示，制动组小鼠在4周时的伸展ROM显著低于非制动组（统计显著性标注不全）；关节囊内的转化生长因子-β1（transforming growth factor-β1）、细胞通信网络因子2（cellular communication network factor 2）与波形蛋白（vimentin）的蛋白表达水平在制动组中显著升高（统计显著性标注不全）。该小鼠模型可作为探究关节挛缩病因学并开发新型治疗方法的有效工具。