Centre for Oral Health Research, Newcastle University, Newcastle upon Tyne, UK.
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Int Endod J. 2019 Feb;52(2):211-222. doi: 10.1111/iej.12997. Epub 2018 Sep 19.
To examine rat molar pulp innervation and identify complex cellular signalling systems involving nerve growth factor (NGF) and its p receptors (NGFR) at different stages of development, maturation and ageing.
Decalcified mandibular first molar mesial cusps from Wistar rats of ages 0 day; 1, 2, 3, 4, 6, 9, 12 and 24 weeks (n = 5 per group) were sectioned (10 μm) and incubated with antibodies for NGF, NGFR, calcitonin gene-related peptide (CGRP) and neurofilament. Nerve densities in worn and intact regions of 3- to 24-week-old rats were compared by anova, Bonferroni and t-tests.
During odontogenesis, differences in NGF and NGFR expression were observed, with no evidence of nerve fibres, suggesting a signalling mechanism controlling cellular differentiation and dentine formation. Tooth wear in 4-week rats was associated with reduced NGF expression and significantly decreased CGRP axons within affected odontoblast regions. The underlying subodontoblasts started expressing NGF which continued until 9 weeks. This may promote a significant increase in CGRP nerve density in affected regions. Nerve density in intact odontoblast regions increased gradually and reached significant levels in 12-week rats. Reduction in nerve densities within worn and intact regions of cusps was observed at 24 weeks.
Age-related changes and responses to tooth wear may be controlled by the NGF signalling mechanism, with roles in odontoblast/subodontoblast communication and control of sensory innervation at different stages of tooth development, maturation and ageing. Greater understanding of cellular and nerve regulation in the injured pulp may promote therapeutic strategies for pulp survival.
研究大鼠磨牙牙髓的神经支配，并在不同的发育、成熟和衰老阶段鉴定涉及神经生长因子（NGF）及其 p 受体（NGFR）的复杂细胞信号系统。
从 0 天、1、2、3、4、6、9、12 和 24 周龄的 Wistar 大鼠下颌第一磨牙近中颊尖收集脱钙的第一磨牙近中颊尖（每组 5 只），并将其切成 10 μm 的切片，然后与 NGF、NGFR、降钙素基因相关肽（CGRP）和神经丝的抗体孵育。通过方差分析、Bonferroni 和 t 检验比较 3 至 24 周龄大鼠磨损和完整区域的神经密度。
在牙发生过程中，观察到 NGF 和 NGFR 表达的差异，没有神经纤维的证据，这表明一种信号机制控制着细胞分化和牙本质形成。4 周龄大鼠的牙齿磨损与 NGF 表达减少和受影响的成牙本质细胞区域内 CGRP 轴突明显减少有关。下方的副成牙本质细胞开始表达 NGF，一直持续到 9 周。这可能会促进受影响区域 CGRP 神经密度的显著增加。完整成牙本质细胞区域的神经密度逐渐增加，并在 12 周龄大鼠中达到显著水平。24 周时观察到牙尖磨损和完整区域的神经密度减少。
年龄相关的变化和对牙齿磨损的反应可能受 NGF 信号机制控制，在牙齿发育、成熟和衰老的不同阶段，在成牙本质细胞/副成牙本质细胞的通讯和感觉神经支配的控制中发挥作用。对损伤牙髓的细胞和神经调节有更深入的了解，可能会促进牙髓存活的治疗策略。
