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(CGRP8-37), such that the inhibitory peptide CGRP(8-37) was overexpressed 4 weeks after induction of joint inflammation in the TMJ of IL-1βXAT 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-1βXAT 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.
|Number of pages||9|
|Journal||Clinical and Experimental Dental Research|
|State||Published - Oct 2022|
Bibliographical noteFunding Information:
We would like to thank Dr. Ross H. Tallents for performing the intra‐articular injections and evaluation of TMJ behavior. We would also like to thank Ms. Jen‐nie H. Miller for cloning and preparation of the FIV viral vectors described herein, and for the evaluation of knee joint behavior. The project was funded in part with NIH grant DE017765 and support from the University of Rochester.
© 2022 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.
- TMJ disorders
- gene therapy
ASJC Scopus subject areas
- Dentistry (all)