Modified Medial Meniscectomy (MMM) Model to Assess Post-Traumatic Knee Osteoarthritis in Mouse

<b>Background/Objectives:</b> Mechanical, physiological, and biochemical changes contribute to post-traumatic osteoarthritis (PTOA). Specific mouse models that are highly reproducible, less invasive, and easy to use are lacking. This limitation hinders the progress of PTOA-related studies on therapeutic applications. The goal of the study was to establish a methodologically innovative, efficient, and less technically challenging surgical model for PTOA. <b>Methods</b>: We developed a modified medial meniscectomy (MMM) model demonstrating high reproducibility and applicability. The MMM model features distinct differences in the execution of transection of the medial meniscus on the lateral side and includes a smaller incision, which enhances reproducibility and is beneficial for studying pain, structure, and function. <b>Results</b>: One month after the MMM surgery, the mice showed increased sensitivity to pain and decreased biomechanical abilities, such as shorter running times and distances. This was further supported by higher Osteoarthritis Research Society International (OARSI) histology scores, a standardized system for determining the severity and extent of OA in cartilage. Additionally, transcriptomic analysis showed an elevated enrichment of immune activity and bone tissue formation gene sets in the knee joint. <b>Conclusions</b>: Overall, functional studies and transcriptomic analyses suggested that the MMM model can be utilized for future biomechanistic and therapeutic applications and could serve as a new resource for studying PTOA.