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 language | English |
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Pages (from-to) | 1158-1166 |
Number of pages | 9 |
Journal | Clinical and Experimental Dental Research |
Volume | 8 |
Issue number | 5 |
DOIs | |
State | Published - 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