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

1 Scopus citations

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

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

  • General Dentistry

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