Proteinases in Enamel Development

Abstract

Proteinases are essential for proper enamel formation. During the secretory stage of enamel development, the ameloblasts responsible for enamel formation secrete enamel matrix proteins including amelogenin (AMELX), ameloblastin (AMBN), enamelin (ENAM), and matrix metalloproteinase-20 (MMP20, enamelysin). MMP20 cleaves the enamel matrix proteins soon after they are secreted and these cleavages are essential because the autosomal recessive inheritance of MMP20 mutations can cause severe enamel defects. Later, during the transition to the early maturation stage of enamel development, kallikrein-related peptidase-4 (KLK4) is secreted by ameloblasts. KLK4 facilitates protein removal, which allows the enamel to mature into its final hardened form. Autosomal recessive inheritance of KLK4 mutations can also cause severe enamel defects consisting of soft enamel that easily abrades from teeth. Recently, pre-secretory ameloblasts and secretory stage ameloblasts were demonstrated to express A Disintegrin And Metallopeptidase Domain-10 (ADAM10). Although ADAM10 may facilitate enamel development, mutations are not known to cause enamel defects in humans primarily because its inactivation is likely embryonic lethal as it is in mice. Nonetheless, as discussed below, the ability of ADAM10 to precisely locate on the cell membrane holds exciting possibilities for how cohorts of secretory stage ameloblasts move relative to one another as enamel development progresses.