Ji Mei, Xiao Lili, Xu Le, Huang Shengyun, Zhang Dongsheng
Department of Stomatology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Exp Ther Med. 2018 Nov;16(5):3759-3765. doi: 10.3892/etm.2018.6728. Epub 2018 Sep 11.
Amelogenesis is a complicated process that concerns the interaction between growing hydroxyapatite crystals and extracellular proteins, which requires the tight regulation of pH. In dental fluorosis, the balance of pH regulation is broken, leading to abnormal mineralization. The current review focuses on the electrolyte transport processes associated with pH homeostasis, particularly regarding the changes in ion transporters that occur during amelogenesis, following exposure to excessive fluoride. Furthermore, the possible mechanism of fluorosis is discussed on the basis of acid hypothesis. There are two main methods by which F accelerates crystal formation in ameloblasts. Firstly, it induces the release of protons, lowering the pH of the cell microenvironment. The decreased pH stimulates the upregulation of ion transporters, which attenuates further declines in the pH. Secondly, F triggers an unknown signaling pathway, causing changes in the transcription of ion transporters and upregulating the expression of bicarbonate transporters. This results in the release of a large amount of bicarbonate from ameloblasts, which may neutralize the pH to form a microenvironment that favors crystal nucleation. The decreased pH stimulates the diffusion of F into the cytoplasm of amelobalsts along the concentration gradient formed by the release of protons. The retention of F causes a series of pathological changes, including oxidative and endoplasmic reticulum stress. If the buffering capacity of ameloblasts facing F toxicity holds, normal mineralization occurs; however, if F levels are high enough to overwhelm the buffering capacity of ameloblasts, abnormal mineralization occurs, leading to dental fluorosis.
釉质形成是一个复杂的过程，涉及生长中的羟基磷灰石晶体与细胞外蛋白质之间的相互作用，这需要对pH进行严格调节。在氟斑牙中，pH调节的平衡被打破，导致矿化异常。本综述重点关注与pH稳态相关的电解质转运过程，特别是在釉质形成过程中，暴露于过量氟化物后离子转运体的变化。此外，基于酸假说讨论了氟中毒的可能机制。氟在成釉细胞中加速晶体形成有两种主要方式。首先，它诱导质子释放，降低细胞微环境的pH。降低的pH刺激离子转运体的上调，这减弱了pH的进一步下降。其次，氟触发一条未知的信号通路，导致离子转运体转录的变化并上调碳酸氢盐转运体的表达。这导致成釉细胞释放大量碳酸氢盐，这可能中和pH以形成有利于晶体成核的微环境。降低的pH刺激氟沿着质子释放形成的浓度梯度扩散到成釉细胞的细胞质中。氟的滞留会引起一系列病理变化，包括氧化应激和内质网应激。如果成釉细胞面对氟毒性的缓冲能力保持，就会发生正常矿化；然而，如果氟水平足够高以至于超过成釉细胞的缓冲能力，就会发生异常矿化，导致氟斑牙。
