MMP-20 mutation in autosomal recessive pigmented hypomaturation amelogenesis imperfecta

Abstract

During mammalian tooth formation, two proteinases are secreted by ameloblasts: enamelysin (MMP-20) and kallikrein-4 (KLK4). Enamelysin is the early protease. It is expressed by ameloblasts throughout the secretory stage and part of the maturation stage.1–3 KLK4 is the late protease; its expression by ameloblasts begins in the transition stage and continues throughout enamel maturation.4,5 Expression of these two proteases overlaps during the transition and early maturation stages, when the bulk of the organic matrix component is removed from the enamel layer. Because of its early pattern of expression, its ability to generate the same pattern of amelogenin cleavages in vitro as those observed in vivo,6 and the nature of the dental phenotype in enamelysin knockout mice,7 MMP-20 cleavages are thought to play important roles in crystal elongation, proper formation of the dentino–enamel junction (DEJ), and in the maintenance of enamel rod organisation. The extracellular protein KLK4 is believed to be the predominant degradative enzyme that clears enamel proteins from the matrix during the maturation stage.8,9,10 There are a number of recent reviews in the literature on the roles of proteolytic enzymes in dental enamel formation.11–14 Enamelysin is a matrix metalloproteinase (MMP). In humans, enamelysin is expressed from a gene on chromosome 11q22.3-q23 having 10 exons (all coding).15 The enamelysin protein has 483 amino acids, including the signal peptide, and folds into propeptide, catalytic, linker, and hemopexin domains.16 The active protease migrates as a doublet at 46 and 41 kDa on zymograms.17,18 Its only post-translational modification is a disulphide bridge connecting the first and last amino acids of the hemopexin domain.19 Inherited enamel malformations show a variety of phenotypes that are grouped according to the thickness and hardness of the enamel layer and are described …