AMTN transgenic mice under the control of the amelogenin gene promoter show a histological appearance similar to that of ameloblasts or supporting cellular structures, while expressions of the enamel proteins AMEL and AMBN are not altered [46]. These results suggest that AMTN plays a primary role in the late stages of enamel mineralization [47]. Apin/ODAM is identified in calcified epithelial odontogenic tumor (CEOT) specimens. Tanespimycin clinical trial Its subcellular localization varies during ameloblast differentiation, though it is stage-specific. Apin/ODAM mRNA is not expressed in pre-ameloblasts and only weakly expressed in secretory ameloblasts, whereas expression is strong in

maturation-stage ameloblasts as well as the junctional epithelium attached to the enamel of erupted molars. In maturation-stage

ameloblasts, Apin/ODAM protein is conspicuous in the supranuclear area (Golgi complex) of smooth-ended ameloblasts as well as in both the supranuclear area and the ruffle end of ruffle-ended ameloblasts. Furthermore, its overexpression and inactivation cause an increase in matrix metalloproteinase-20 (MMP-20) expression and a decrease in tuftelin expression, indicating that Apin/ODAM plays a functional role in enamel mineralization and maturation that is mediated by the expression of MMP-20 and Ibrutinib tuftelin [48]. The Apin/ODAM gene is highly conserved in mammals, while it is absent in fish, birds, and amphibians, as seen with AMTN [49]. The Apin/ODAM protein is modified in a post-translational

manner, which is consistent with the presence of predicted sites for phosphorylation and O-linked glycosylation. The presence of Apin/ODAM at cell-tooth interfaces suggests that it is involved in adhesive mechanisms active at these sites, while its presence in other epithelial tissues indicates that it likely possesses broader physiological roles [49]. The expression of Apin/ODAM click here is increased in the secretory-stage ameloblasts of AMTN transgenic animals, indicating that AMTN may regulate its expression [46]. Both Apin/ODAM and AMTN are localized in the basal lamina of maturation-stage ameloblasts. At the beginning of maturation, a concentration of Apin/ODAM exists on the cell side of the basal lamina, while AMTN appears to be more concentrated on the enamel side. In the late maturation stage, such differential distribution is no longer apparent [50]. Using two-yeast hybrid screening systems, AMTN interacts with itself and ODAM, but not with AMEL, AMBN, or ENAM. Using ODAM as bait, the interaction with AMTN is confirmed. ODAM binds to itself and AMBN, as well as weakly to AMEL, but not to ENAM. The distinct expressions of AMTN and ODAM and their interaction are involved in defining the enamel microstructure on the enamel’s surface [51]. Most ECM proteins contain domain structures such as EGF-like, fibronectin type III (FN3), laminin G (LamG), Ig-like, thrombospondin (TSPN), von Willebrand factor A (VWA), and collagenous domains.