Human odontoblasts express functional thermo-sensitive TRP channels: Implications for dentin sensitivity
Human odontoblasts express functional thermo-sensitive TRP channels: Implications for dentin sensitivity
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DOI：
10.1016/j.pain.2010.10.016
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发表时间：
2011-10-01
期刊：
影响因子：
7.4
通讯作者：
Lundy, Fionnuala T.
中科院分区：
文献类型：
--
作者：
El Karim, Ikhlas A.;Linden, Gerard J.;Lundy, Fionnuala T.
成牙本质细胞形成牙髓的最外层细胞层，在那里它们被认为是感觉受体细胞。尽管这一建议，证据支持他们在介导的温度感觉和伤害性感受的直接作用是缺乏的。瞬时受体电位（TRP）离子通道直接介导伤害性感受功能，但其在人成牙本质细胞中的功能表达尚未阐明。在本研究中，我们研究了培养的成牙本质细胞样细胞和从健康智齿中获得的天然人成牙本质细胞中温度敏感TRP通道的分子和功能表达。PCR和Western blotting证实了TRPV1、TRPA1和TRPM8通道基因和蛋白的表达。免疫组化显示，这些通道定位成牙本质细胞样细胞与牙本质唾液蛋白（DSP）抗体的双重染色确定。在功能测定中，TRPV 1、TRPA 1和TRPM 8通道的激动剂引起[Ca 2 +]（i）瞬变，其可被相关拮抗剂阻断。冷热刺激的应用也引起了[Ca 2 +] i的升高，这可以被TRP通道拮抗剂阻断。使用基因沉默方法，我们进一步证实了TRPA1在介导成牙本质细胞的有害冷反应中的作用。我们的结论是，人类成牙本质细胞表达功能性TRP通道，可能在介导牙齿的热感觉中发挥至关重要的作用。(C)2010年国际疼痛研究协会。由Elsevier B出版。V.保留所有权利。
Odontoblasts form the outermost cellular layer of the dental pulp where they have been proposed to act as sensory receptor cells. Despite this suggestion, evidence supporting their direct role in mediating thermo-sensation and nociception is lacking. Transient receptor potential (TRP) ion channels directly mediate nociceptive functions, but their functional expression in human odontoblasts has yet to be elucidated. In the present study, we have examined the molecular and functional expression of thermo-sensitive TRP channels in cultured odontoblast-like cells and in native human odontoblasts obtained from healthy wisdom teeth. PCR and western blotting confirmed gene and protein expression of TRPV1, TRPA1 and TRPM8 channels. Immunohistochemistry revealed that these channels were localised to odontoblast-like cells as determined by double staining with dentin sialoprotein (DSP) antibody. In functional assays, agonists of TRPV1, TRPA1 and TRPM8 channels elicited [Ca2+](i) transients that could be blocked by relevant antagonists. Application of hot and cold stimuli to the cells also evoked rises in [ Ca2+] i which could be blocked by TRP-channel antagonists. Using a gene silencing approached we further confirmed a role for TRPA1 in mediating noxious cold responses in odontoblasts. We conclude that human odontoblasts express functional TRP channels that may play a crucial role in mediating thermal sensation in teeth. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.