A standardized, open-source, portable model for noninvasive joint injury in mice

Abstract

Objective

Preclinical models of osteoarthritis (OA) are crucial for the study of disease mechanisms and development of disease-modifying therapeutics. While surgical OA models, such as destabilization of the medial meniscus (DMM), have been the gold standard in the field for decades, noninvasive joint loading-based models have increased in popularity and utility. To facilitate standardization of the noninvasive anterior cruciate ligament rupture (ACLR) model in mice, we present the Mobile Joint-Injury Operator (MoJO) - an open-source protocol with accompanying fixtures and data, designed for a low-cost, commercially-available, portable, small-footprint uniaxial testing system.

Methods

We provide 3d-printable fixture designs and a comprehensive description of the loading protocol, describe the expected mechanical output, and offer various troubleshooting strategies. We validate the mechanical accuracy and inter-operator reproducibility of the procedure and characterize the resultant post-traumatic OA phenotype by knee hyperalgesia testing, flow cytometry, μCT imaging, and histological assessment.

Results

Across n ​= ​952 procedures, the MoJO protocol was highly accurate and repeatable, with a >99 ​% rate of successful ACLR and high repeatability between operators and institutions. ACLR-mediated joint injury resulted in the expected post-traumatic OA phenotype in male and female C57Bl/6 mice, including progressive hyperalgesia, histological and μCT evidence of cartilage damage, synovitis, and osteophyte formation, and increased expansion of fibroblasts, endothelial cells, and myeloid cells by flow cytometry.

Conclusions

Increased standardization of joint injury is a critical aspect of the overall refinement of animal models of OA. The MoJO represents an affordable and highly reproducible option for implementing the mouse ACLR model of OA.