The different matrix components in enamel contribute to its larger and more rigid hydroxyapatite crystal structures than dentin and bone. Enamel matrix proteins are produced at their highest levels by ameloblasts

during the secretory and transition stages of amelogenesis and collectively orchestrate the proper assembly and growth small molecule library screening of crystals within mineralized enamel. These proteins are nearly completely degraded by specific proteases such as MMP-20, mainly produced during the secretory/transition stage, and KLK4, mainly produced during the transition/maturation stage, resulting in a highly ordered and purposefully designed meshwork of carbonated hydroxyapatite crystals with astonishing mechanical properties [1]. Cell adhesion to the extracellular matrix is of fundamental importance for a wide range of cellular functions, including cell differentiation, proliferation, and survival [2]. Inner and outer enamel epithelial cells interact with the basement membrane, of which major constituents are type IV collagen, laminin, and heparan-sulfate proteoglycan perlecan. For example, laminin α5 (Lama5)-deficient mice show small tooth germs without a cusp [3]. In addition, proliferation and polarization of the dental epithelium

are inhibited in these Raf inhibitor mice, indicating that interactions between the dental epithelium and the basement membrane are important to determine tooth sizes and dental epithelial cell differentiation. Ameloblasts are polarized in the secretory stage and secrete enamel matrix components, including amelogenin (AMEL), ameloblastin (AMBN), and enamelin (ENAM). Furthermore, amelotin (AMTN) and Apin/odontogenic ameloblast-associated (ODAM) are secreted from those

in the maturation stage. These enamel matrix components are considered important for enamel crystal formation. In fact, AMEL and ENAM mutations are identified in patients with amelogenesis imperfecta (AI), a common group of inherited defects of dental enamel formation that exhibit marked genetic and clinical Gemcitabine order heterogeneity, with at least 14 different sub-types recognized on the basis of their clinical appearance and mode of inheritance [4], [5] and [6]. However, a recent study that used a gene-targeting method and in vitro analysis showed that these matrices also have a large number of biological functions in addition to enamel formation, including bone formation, tumorigenesis, and the regulation of stem cell function. Mineralized tissue formation and maintenance are controlled by matrix proteins such as several secretory calcium-binding phospho-proteins (SCPPs), which are encoded by SCPP genes clustered on human chromosome 4 [7]. Half of these proteins, including bone sialoprotein, osteopontin, dentin sialophosphoprotein, and dentin matrix protein, are associated with bone and dentin formation, while the other half of consists of enamel-associated proteins, including AMBN, ENAM, AMTN, and Apin/ODAM (Table 1).