Clinical and experimental dental research · 2022
Calcitonin gene-related peptide: An intra-articular therapeutic target for TMJ disorders.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Brouxhon Sabine M, O'Banion M Kerry, Dickerson Ian M, Kyrkanides Stephanos
Аннотация
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.
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.