Neural crest-specific disruption of Evc2 provides an animal model to study the temporomandibular joint (TMJ) development and homeostasis in response to jaw loading.

Abstract

The temporomandibular joint (TMJ), essential for jaw movements, is susceptible to osteoarthritis (TMJ-OA), impacting a significant portion of the population. This study introduces an innovative genetic mouse model to explore TMJ development, maintenance, and interactions with the mechanical environment. We exploited Evc2/Limbin conditional knockout (Evc2 cKO) mice, specifically targeting neural crest cell-derived tissues (Wnt1Cre), to observe TMJ development. Disruption of Evc2 in neural crest cells contributed to morphological changes in the TMJ growth plate cartilage layers, predisposing the joint components to defects. Condyle defective regions presented a unique environment composed of cartilage, bone, stem cells, and an augmented polymorphic layer. Our findings further revealed that the Evc2 cKO mice presented TMJ components degeneration clinically like those observed in human TMJ-osteoarthritis (OA). Mandible condyle gene expression analysis showed augmented expression of general inflammatory and OA markers. Supplying the mice with regular chow (RD) worsens the phenotype, but soft chow (SD)-fed partially rescued both condyle morphology and intra-articular space. The data suggest that changes in the loading environment critically affect the integrity and functionality of the TMJ, with direct implications for its preservation and disease management.