Standardized Instability-induced Animal Models for Preclinical Studies of Osteoarthritis.

Abstract

As the most prevalent joint disorder worldwide, knee osteoarthritis (OA) represents a significant global health burden, prompting extensive research into its pathogenesis and treatment strategies. Despite numerous studies, standardized methodologies for model establishment remain lacking. Thus, to address this gap, we present comprehensive, reproducible protocols for developing instability-induced animal models of osteoarthritis, specifically the Destabilization of the Medial Meniscus (DMM) model in mice and the Medial Meniscus Tear (MMT) model in rats. Furthermore, we describe a straightforward and easily implementable procedure for assessing postoperative pain thresholds and spatial gait stability, aimed at promoting methodological consistency in preclinical OA research. Histological and behavioral validation confirmed the success of both models, as Osteoarthritis Research Society International (OARSI) scores were markedly elevated, stride length was significantly altered, and mechanical pain thresholds were substantially reduced in the DMM and MMT groups compared with controls, indicating pronounced joint degeneration and hypersensitivity. These validation outcomes underscore the reproducibility and translational relevance of the two models. Thus, by providing detailed video documentation, this work promotes procedural standardization and facilitates inter-laboratory consistency, thereby enhancing the reliability and comparability of OA research outcomes.