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.已有多项研究采用动物模型探究膝关节挛缩，但鲜有文献详细阐述小鼠膝关节挛缩模型的构建流程。采用小鼠模型具有显著优势：可利用基因工程改造小鼠研究关节挛缩的发病机制，且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。本研究介绍一种新型的通过外固定制动构建的小鼠膝关节挛缩模型，具体为采用夹板与胶带实施外固定以固定小鼠膝关节。本研究对制动组（Im组）与非制动组（Non-Im组）小鼠在造模后2周及4周时的被动伸展活动度（passive extension range of motion, 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进行了对比分析。结果显示，造模4周时制动组小鼠的伸展活动度显著低于非制动组（p<0.05）；关节囊内转化生长因子-β1（transforming growth factor-β1）、细胞通讯网络因子2（cellular communication network factor 2）及波形蛋白（vimentin）的蛋白表达水平在制动组中显著升高（p<0.05）。该小鼠模型可作为探究关节挛缩病因及开发新型治疗手段的有效工具。