Scientists at the University of Southern California have identified a small region of the ameloblastin protein that plays an important role in the formation of the proper structure of tooth enamel. Experiments in genetically modified mice showed that without this region, enamel can reach nearly normal thickness but loses its characteristic internal architecture and becomes significantly less mineralized. The findings were published in the International Journal of Oral Science.
Enamel is the hardest tissue in the human body. At first glance, it appears to be a smooth surface, but under a microscope it has a complex, highly organized structure consisting of enamel rods and interrod substance. It is formed by elongated cells called ameloblasts, which acquire a specific shape and polarity as enamel develops. Until now, scientists have not fully understood the molecular mechanism that helps these cells orient themselves correctly and organize the tissue they produce.
Professor Janet Moradian-Oldak of the University of Southern California and her colleagues focused on ameloblastin (Ambn), the second most abundant extracellular matrix protein in developing enamel. The researchers studied a small region of this protein that forms an amphiphilic helix and is capable of interacting with cell membranes. Nine of the 11 amino acids in this region are identical in mice, pigs, and humans, indicating that it is evolutionarily conserved.
Using CRISPR-Cas9 technology, the scientists created mice in which hydrophobic amino acids in this region of ameloblastin were deleted. Additional experiments showed that the mutation did not destroy the protein itself: the altered ameloblastin was still able to assemble into structures on its own. However, its ability to interact with ameloblast-lineage cells was significantly reduced.
The researchers also detected changes in several signaling pathways, including Wnt, TGF-β, and RhoA-ROCK, which may be involved in regulating cell polarity and tissue organization. Even mice carrying only one altered copy of the gene showed abnormalities in enamel architecture and cell polarity, although the mineral density of the enamel remained normal.
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