Proposing a mouse model to study temporomandibular joint disorders using mutations in Evc2/LIMBIN gene – UROP Symposium

Proposing a mouse model to study temporomandibular joint disorders using mutations in Evc2/LIMBIN gene

Nicholas Yiu

Pronouns: he/him/his

Research Mentor(s): Yuji Mishina
Research Mentor School/College/Department: Biological and Material Sciences / Dentistry
Program:
Authors: Nicholas Yiu, Rafael Correia Cavalcante, Yuji Mishina
Session: Session 5: 2:40 pm – 3:30 pm
Poster: 104

Abstract

The goal of this study is to introduce a new mouse model tailored to explore osteoarthritis in the temporomandibular joint (TMJ-OA), by studying the structural and functional changes in the TMJ following mutations in Evc2. EVC2 is a ciliary protein found on cell membranes important for bone formation and skeletal development through growth factor and mechanosensor signaling. The TMJ is a complex structure composed of bones, cartilage, and muscles. The Cre-loxP system was utilized to conditionally knockout the Evc2 gene using a neural crest cell enhancer. Evc2fx; Wnt1-Cre mutant mice were subjected to either a hard diet (HD, regular diet) or soft diet (SD) for a period of 4 weeks. Histological analysis showed that mutant mice fed with HD presented degenerative defects such as degeneration of the mandible condyle and TMJ disc, resembling TMJ-OA. Mutants fed with a SD, however, presented joint components similar to controls (Evc2fx/+; Wnt1-Cre) highlighting the crucial role of mechanosensing on the pathogenesis of the condition. Functional experiments found that mutants fed with HD presented TMD symptoms such as a decrease in chewing rate, displacement, bite force, and an increase in pain levels. Micro-CT scans further showed anterior dislocation of mandible condyle resulting in premature contact with the temporal bone leading and possibly anterior displacement of the disc. A two-week SD treatment, however, was shown to rescue TMJ-OA degeneration and TMD symptoms. The results of this study show that Evc2 mutations are promising as small animal models for studying TMJ-OA and TMD, since structural abnormalities associated with function commitment were achieved in mutants.

Biomedical Sciences

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