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

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

doi:10.1002/cre2.606

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

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

Oral Health Science

Research output: Contribution to journal › Article › peer-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(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.

Original language	English
Pages (from-to)	1158-1166
Number of pages	9
Journal	Clinical and Experimental Dental Research
Volume	8
Issue number	5
DOIs	https://doi.org/10.1002/cre2.606
State	Published - Oct 2022

Bibliographical note

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

Funding

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.

Funders	Funder number
National Institutes of Health (NIH)
National Institute of Dental and Craniofacial Research	R21DE017765
National Institute of Dental and Craniofacial Research
University of Minnesota Rochester

Keywords

CGRP
TMJ disorders
gene therapy
osteoarthritis

ASJC Scopus subject areas

General Dentistry

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10.1002/cre2.606

Cite this

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title = "Calcitonin gene-related peptide: An intra-articular therapeutic target for TMJ disorders",

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.",

keywords = "CGRP, TMJ disorders, gene therapy, osteoarthritis",

author = "Brouxhon, {Sabine M.} and O'Banion, {M. Kerry} and Dickerson, {Ian M.} and Stephanos Kyrkanides",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.",

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doi = "10.1002/cre2.606",

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volume = "8",

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AU - O'Banion, M. Kerry

AU - Dickerson, Ian M.

AU - Kyrkanides, Stephanos

PY - 2022/10

Y1 - 2022/10

N2 - 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.

AB - 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.

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KW - gene therapy

KW - osteoarthritis

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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