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

Calcitonin gene-related peptide: An intra-articular therapeutic target for TMJ disorders.
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DOI:
10.1002/cre2.606
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发表时间:
2022-10
影响因子:
1.8
通讯作者:
Kyrkanides S
Kyrkanides S
中科院分区:
其他
文献类型:
--
作者:
Brouxhon SM;O'Banion MK;Dickerson IM;Kyrkanides S

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该项目的目标是评估降钙素基因相关肽(CGRP)在关节炎发生中的作用。在本文中,我们通过在年轻成年雄性C57/BL 6小鼠的膝关节或颞下颌关节(TMJ)中进行FIV(CGRP)关节内接种,在两个不同关节中进行体细胞镶嵌分析。FIV(CGRP)是一种过表达全长CGRP的猫免疫缺陷病毒。在组织病理学和行为学水平上评价关节病理学和功能。此外,通过使用FIV(CGRP 8 - 37)的关节内接种抑制CGRP信号传导,使得在IL-1βXAT转基因小鼠模型的TMJ中诱导关节炎症后4周抑制肽CGRP(8 - 37)过表达。评价小鼠的行为并处死以评价膝关节和TMJ病理学。CGRP在野生型小鼠关节中的过表达诱导了关节异常的发展,包括与伤害性行为相关的关节肥大和关节病理学。有趣的是,在患有关节炎的IL-1βXAT转基因小鼠的膝关节和TMJ中过表达CGRP(8 - 37)抑制肽导致伴随的关节病理学部分改善。这项研究的结果表明,CGRP对于关节病理学的发展是充分和必要的,并且可以作为使用基因治疗或基于单克隆抗体的治疗的关节内治疗靶点。
The goal of this project was to evaluate the role of calcitonin gene‐related peptide (CGRP) in the development of arthritis. 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. 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. 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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