A reproducible mouse model of TMJ anterior disc displacement

Abstract Temporomandibular joint disorders (TMD) are a group of clinical conditions characterized by chronic jaw dysfunction and persistent orofacial pain, affecting approximately one-third of the adult population. Anterior displacement of the articular disc (ADD), which leads to joint instability and mechanical overload, is strongly linked to arthrogenous TMD. However, the cellular and molecular mechanisms triggered by ADD, and how they contribute to joint derangement, remain poorly understood. Clinical treatments for this chronic condition are also limited. Although several animal models exist for ADD, most are difficult to validate and rely on species that lack advanced genetic tools. To address this, we developed a reproducible and compatible surgical murine model of ADD, which is suitable for lineage tracing, reporter analyses, and gene modification techniques. Here, we describe a procedure for generating unilateral surgical ADD in adult mice and validate this model using magnetic resonance imaging (MRI). Whole-mount skeletal staining and histology reveal degeneration of the condylar cartilage, erosion of the temporal bone, and disc fibrosis by 15 d post-surgery (dps), compared to controls. Overall, this genetically tractable murine model offers a powerful platform for dissecting the mechanisms of ADD and identifying new cellular and molecular targets for TMD therapy.