Enamel Matrix Biomineralization: The Role of pH Cycling

Abstract

Dental enamel, which is the most highly mineralized tissue in the human body, is critically important for the protection of the underlying tooth structures throughout a lifetime. When enamel is absent or poorly formed due to genetic defects, called amelogenesis imperfecta (AI), or through environmental or epigenetic effects such as fluorosis, or lost due to dental caries, the entire tooth structure may be compromised. Ameloblasts differentiate through secretory, transition, and maturation stages to generate the fully mineralized enamel matrix. Enamel matrix proteins produced during the secretory stage undergo limited hydrolyzed by matrix metalloproteinase 20 (MMP20) to initiate crystal growth. Then during maturation, the remaining matrix proteins are completely hydrolyzed by kallikrein 4 (KLK4). The protein fragments are endocytosed and this allows complete mineralization of the enamel space. Enamel mineralization is unique in that it requires pH cycling, in which the ameloblasts modulate the matrix pH between an acidic and neutral pH. In this chapter, Part 1 is an overview of enamel formation, and how pH cycling influences amelogenin hydrolysis by KLK4 and enamel mineralization. Part 2 describes how ion-pumps and transporters regulate the enamel matrix pH as mineralization occurs.