Department of Oral Biology, Semmelweis University, Budapest, Hungary.
Department of Orofacial Sciences, University of California, San Francisco, CA, USA.
Oral Dis. 2018 Sep;24(6):879-890. doi: 10.1111/odi.12738. Epub 2017 Sep 18.
Dental enamel, the hardest mammalian tissue, is produced by ameloblasts. Ameloblasts show many similarities to other transporting epithelia although their secretory product, the enamel matrix, is quite different. Ameloblasts direct the formation of hydroxyapatite crystals, which liberate large quantities of protons that then need to be buffered to allow mineralization to proceed. Buffering requires a tight pH regulation and secretion of bicarbonate by ameloblasts. Many investigations have used immunohistochemical and knockout studies to determine the effects of these genes on enamel formation, but up till recently very little functional data were available for mineral ion transport. To address this, we developed a novel 2D in vitro model using HAT-7 ameloblast cells. HAT-7 cells can be polarized and develop functional tight junctions. Furthermore, they are able to accumulate bicarbonate ions from the basolateral to the apical fluid spaces. We propose that in the future, the HAT-7 2D system along with similar cellular models will be useful to functionally model ion transport processes during amelogenesis. Additionally, we also suggest that similar approaches will allow a better understanding of the regulation of the cycling process in maturation-stage ameloblasts, and the pH sensory mechanisms, which are required to develop sound, healthy enamel.
牙釉质是哺乳动物最坚硬的组织,由成釉细胞产生。尽管成釉细胞的分泌产物——釉基质与其他分泌性上皮组织有许多相似之处,但它们的分泌产物——釉基质却大不相同。成釉细胞指导羟磷灰石晶体的形成,这些晶体释放出大量质子,然后需要缓冲质子以允许矿化进行。缓冲作用需要严格的 pH 调节和成釉细胞分泌的碳酸氢盐。许多研究已经使用免疫组织化学和基因敲除研究来确定这些基因对釉质形成的影响,但直到最近,关于矿物质离子转运的功能数据非常有限。为了解决这个问题,我们开发了一种使用 HAT-7 成釉细胞的新型 2D 体外模型。HAT-7 细胞可以极化并形成功能性紧密连接。此外,它们能够从基底外侧向顶端腔室空间积累碳酸氢盐离子。我们提出,在未来,HAT-7 2D 系统以及类似的细胞模型将有助于在釉质发生过程中对离子转运过程进行功能建模。此外,我们还建议类似的方法将有助于更好地理解成熟阶段成釉细胞的循环过程的调节以及 pH 感应机制,这些机制对于发育出健康、完好的牙釉质是必需的。