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

Abstract

Preclinical models of osteoarthritis (OA) are crucial for the study of disease mechanisms and for the development of critically-needed disease-modifying therapeutics. While surgical OA models, such as the 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 uniaxial testing system with a small footprint. We provide 3d-printable fixture designs and a rapid, highly-repeatable ACLR-mediated joint injury protocol that results in the expected post-traumatic osteoarthritis phenotype in male and female C56Bl/6 mice. We then describe the expected mechanical data from the injury procedure and offer various troubleshooting strategies. Finally, we summarize the resultant PTOA phenotype by knee hyperalgesia testing, {micro}CT imaging, flow cytometry, and histological assessment. Increased standardization of this model is a critical aspect of the overall refinement of animal models of OA.