School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK Laboratoire IMEB, Faculté d Odontologie, Université de la Méditerranée, Marseille, France.
Pain. 2011 Oct;152(10):2211-2223. doi: 10.1016/j.pain.2010.10.016. Epub 2010 Dec 17.
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. Cultured and native human odontoblasts express functional TRP channels that may play a crucial role in mediating thermal sensation in teeth.
成牙本质细胞形成牙髓的最外层细胞层,在那里它们被提议作为感觉受体细胞。尽管有这种说法,但缺乏支持它们在介导热敏和伤害感受中直接作用的证据。瞬时受体电位 (TRP) 离子通道直接介导伤害感受功能,但它们在人成牙本质细胞中的功能表达尚未阐明。在本研究中,我们检查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热敏 TRP 通道的分子和功能表达。PCR 和 Western blot 证实了 TRPV1、TRPA1 和 TRPM8 通道的基因和蛋白表达。免疫组织化学显示这些通道定位于成牙本质细胞样细胞,如用牙本质涎蛋白 (DSP) 抗体双重染色所确定的。在功能测定中,TRPV1、TRPA1 和 TRPM8 通道的激动剂可引发 [Ca2+]i 瞬变,可被相关拮抗剂阻断。将热和冷刺激应用于细胞也可引起 [Ca2+]i 的升高,可被 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中有害冷反应中的作用。我们得出结论,人成牙本质细胞表达功能性 TRP 通道,这些通道可能在介导牙齿的热感觉中发挥关键作用。培养的和天然的人成牙本质细胞表达功能性 TRP 通道,这些通道可能在介导牙齿的热感觉中发挥关键作用。