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

ABSTRACT

Aims

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.

Methods

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.

Results

The extension ROM at 4 weeks was significantly lower in the Im group than in the Non-Im group (p < 0.01). At 2 and 4 weeks, the thickness and area of the joint capsule were significantly greater in the Im group than in the Non-Im group (p < 0.01 in all cases). At 2 weeks, the mRNA expression levels of the fibrosis-related genes, except for the 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 < 0.01 in all cases).

Conclusion

This mouse model may serve as a useful tool to investigate the etiology of joint contracture and establish new treatment methods.

KEYWORDS:

• Joint contracture
• mouse model
• knee joint
• external fixation
• joint capsule

Acknowledgments

The authors are grateful to Dr. Motokuni Aoki, Dr. Hirohisa Kawahata, and Dr. Daisuke Sotobayashi from the Graduate School of Health Sciences, Morinomiya University of Medical Sciences for their technical assistance in generating the knee contracture mouse model.

Authors’ contribution

All authors confirmed that they have contributed to the intellectual content of this paper and have met the following three requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval to publish the article.

Disclosure statement

The authors have no conflicts of interest directly relevant to the content of this article.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This study was supported by grants from JSPS KAKENHI Grant Number [JP20K18047].