Calcitonin gene‐related peptide: An intra‐articular therapeutic target for TMJ disorders

OBJECTIVES: The goal of this project was to evaluate the role of calcitonin gene‐related peptide (CGRP) in the development of arthritis. METHODS: Herein, we employed somatic mosaic analysis in two different joints by FIV(CGRP) intra‐articular inoculation in the knees or temporomandibular joints (TMJ) of young adult male C57/BL6 mice. FIV(CGRP) is a feline immunodeficiency virus over‐expressing full‐length CGRP. Joint pathology and function were evaluated at the histopathological and behavioral levels. In addition, CGRP signaling was inhibited by intra‐articular inoculation using FIV(CGRP(8‐37)), such that the inhibitory peptide CGRP(8‐37) was overexpressed 4 weeks after induction of joint inflammation in the TMJ of IL‐1β(XAT) transgenic mouse model. The mice were evaluated for behavior and killed for evaluation of knee and TMJ pathology. RESULTS: Overexpression of CGRP in the joints of wild‐type mice induced the development of joint anomalies, including meniscal hypertrophy and articular pathology, associated with nocifensive behavior. Intriguingly, overexpression of the CGRP(8‐37) inhibitory peptide in the knee and TMJ of IL‐1β(XAT) transgenic mice with joint inflammation resulted in partial amelioration of the attendant joint pathology. CONCLUSIONS: The results of this study suggest that CGRP is sufficient and necessary for the development of joint pathology and may serve as an intra‐articular therapeutic target using gene therapy or monoclonal antibody‐based therapies.