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CGRP and Shh Mediate the Dental Pulp Cell Response to Neuron Stimulation
Journal of Dental Research ( IF 7.6 ) Pub Date : 2022-04-11 , DOI: 10.1177/00220345221086858
E R Moore 1 , B Michot 1 , O Erdogan 1 , A Ba 1 , J L Gibbs 1 , Y Yang 1
Affiliation  

Dental pain is a persistent, detrimental public health issue that requires a better understanding of the mechanisms of tooth pain and inflammation in order to develop more effective treatments. Calcitonin gene-related peptide (CGRP) and dental pulp cells are promising candidates for mediating tooth pain and generating reparative dental tissues, respectively, but their behavior in the context of pulpitis remains elusive. The mouse incisor requires Sonic hedgehog (Shh) secreted from sensory nerves to continuously regenerate. However, it is unknown whether sensory nerves also regulate the comparatively nonregenerative mouse molar through CGRP and Shh. This is an important knowledge gap to fill since mouse incisors differ biologically from human teeth, while mouse and human molars are similar. In this work, we identified that molar pulp cells express CGRP receptor and Gli1, a Hedgehog (Hh) signaling protein found to label a dental stem cell population in the mouse incisor. We also observed in a mouse molar injury model that Hh signaling was activated and Shh expression was upregulated in vivo. We then determined in vitro that Shh and CGRP regulate differentiation of primary mouse molar and incisor pulp cells and a human dental pulp stem cell line. Furthermore, conditioned media from stimulated sensory neurons induced Hh signaling activation and inflammatory gene expression in primary molar pulp cells, which was abolished by inhibition of either Shh or CGRP. Our results suggest that CGRP and Shh signaling may promote an inflammatory response after injury in the molar and that activated sensory nerves secrete CGRP and Shh to regulate molar pulp cell expansion and differentiation into odontoblast-like cells for dentin repair. Thus, CGRP/Shh signaling should be considered for new strategies that seek to manage pain or dentin regeneration in the molar.



中文翻译:

CGRP 和 Shh 介导牙髓细胞对神经元刺激的反应

牙痛是一个持续存在的、有害的公共健康问题,需要更好地了解牙痛和炎症的机制,以便开发更有效的治疗方法。降钙素基因相关肽(CGRP)和牙髓细胞分别是介导牙齿疼痛和生成修复性牙组织的有希望的候选者,但它们在牙髓炎中的行为仍然难以捉摸。小鼠门牙需要感觉神经分泌的音刺猬(Shh)来不断再生。然而,尚不清楚感觉神经是否也通过 CGRP 和 Shh 调节相对不可再生的小鼠磨牙。这是一个需要填补的重要知识空白,因为小鼠门牙在生物学上与人类牙齿不同,而小鼠和人类臼齿相似。在这项工作中,我们发现磨牙牙髓细胞表达 CGRP 受体和 Gli1,Gli1 是一种 Hedgehog (Hh) 信号蛋白,被发现可以标记小鼠门牙中的牙干细胞群。我们还在小鼠磨牙损伤模型中观察到体内 Hh 信号被激活且 Shh 表达上调。然后,我们在体外确定了Shh和CGRP调节原代小鼠磨牙和切牙牙髓细胞以及人牙髓干细胞系的分化。此外,来自受刺激感觉神经元的条件培养基诱导初级磨牙牙髓细胞中的 Hh 信号激活和炎症基因表达,而这可以通过抑制 Shh 或 CGRP 来消除。我们的结果表明,CGRP 和Shh 信号传导可能促进磨牙损伤后的炎症反应,并且激活的感觉神经分泌CGRP 和Shh 来调节磨牙牙髓细胞扩张和分化为成牙本质细胞样细胞以进行牙本质修复。因此,应考虑将 CGRP/Shh 信号转导用于寻求控制磨牙疼痛或牙本质再生的新策略。

更新日期:2022-04-11
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