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

Sabine M. Brouxhon, M. Kerry O'Banion, Ian M. Dickerson, Stephanos Kyrkanides

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1158-1166
Number of pages9
JournalClinical and Experimental Dental Research
Volume8
Issue number5
DOIs
StatePublished - Oct 2022

Bibliographical note

Funding 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.

Publisher Copyright:
© 2022 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.

Keywords

  • CGRP
  • TMJ disorders
  • gene therapy
  • osteoarthritis

ASJC Scopus subject areas

  • Dentistry (all)

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