Establishment of a reliable and reproducible murine osteoarthritis model

Abstract

Many osteoarthritis (OA) models have been developed in mice to understand OA progression and evaluate new OA therapies. However, the individual variation of the joint lesions remains a critical problem in most of the current OA models. We established an OA model in C57BL/6 mice that is more reproducible and amenable to therapeutic intervention by controlling their movement. OA was induced in 9-week-old C57BL/6 mice by destabilizing the medial meniscus. The mice were then raised in the standard cage for free movement or in a confined cage customized to restrict movement. Mice in the confined cage were subjected to no exercise or exercise of 400, 800, and 1200 m/day. OA lesions of mice in the confined cage were more severe in the exercise group and showed much less variation. However, the patterns of OA lesions over time were quite different depending on the amount of daily exercise; the patterns increased linearly until 8 weeks in 400 m/day exercise group, but showed plateauing after 4 weeks in 800 m/day and 1200 m/day groups. The validity of our novel OA model with movement control was proven by successfully discriminating the therapeutic effect of hyaluronic acid (HA) in histological scores, while the OA model using standard caging showed a statistically insignificant difference. The mouse OA model using the confine cage and enforced periodic exercise of mice is more reproducible and reliable than standard caging methods.