Matrix and Mineral Changes in Developing Enamel

To create a bioceramic with unique materials properties, biomineralization exploits cells to create a tissue-specific protein matrix to control the crystal habit, timing, and position of the mineral phase. The biomineralized covering of vertebrate teeth is enamel, a distinctive tissue of ectodermal origin that is collagen-free. In forming enamel, amelogenin is the abundant protein that undergoes self-assembly to contribute to a matrix that guides its own replacement by mineral. Conserved domains in amelogenin suggest their importance to biomineralization. We used gene targeting in mice to replace native amelogenin with one of two engineered amelogenins. Replacement changed enamel organization by altering protein-to-crystallite interactions and crystallite stacking while diminishing the ability of the ameloblast to interact with the matrix. These data demonstrate that ameloblasts must continuously interact with the developing matrix to provide amelogenin-specific protein to protein, protein to mineral, and protein to membrane interactions critical to biomineralization and enamel architecture while suggesting that mutations within conserved amelogenin domains could account for enamel variations preserved in the fossil record.In mammals mesenchyme-derived bone is the dominant biomineralized tissue and is composed of substituted hydroxyapatite crystals with specific proteins distributed in an abundant collagen network (1-3). For bone, the mineral composite is dynamic with both the protein and mineral phases being constantly remodeled by cells. A notable exception to such a biomineralization theme is found in enamel, the vertebrate covering of teeth. In teeth, ectoderm-derived ameloblasts synthesize a short-lived, diverse repertoire of proteins that self-assemble to produce a matrix that directs its own replacement by the mineral phase (4, 5). Mature enamel is a bioceramic composed of less than 0.5% protein that is dispersed among the longest hydroxyapatite crystals in the vertebrate body (6 -8). Unlike mesenchyme-derived bone, enamel does not contain collagen, does not have the capacity of self-repair, and does not undergo remodeling. Nonetheless, enamel lasts the lifetime of the organism due its unique material properties and remarkable resistance to failure (9, 10). These properties are due in part to the cell-directed organization of crystallites into bundles called rods. Rods are further woven together during their formation by cell migration to form a unique three-dimensional lattice architecture that resists wear and deformation (9 -14).Amelogenin is the most abundant of the enamel matrix proteins and undergoes self-assembly to form nanospheres (15-17). Amelogenin nanospheres appear to control the habit of hydroxyapatite crystallites by directing mineral growth to the ends (cЈ axis) of the crystallites by providing the space for crystallites to grow within and by buffering the local environment against protons liberated during mineral deposition (5, 7, 18 -20). The amino acid sequence of amelogenin is highly ...

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Altering Biomineralization by Protein Design

Zhu

Paine

Luo

et al. 2006

“…The microenvironment of amelogenin in the developing enamel includes proteinases (7,16,63,64). Indeed, amelogenin is fragmented by these proteinases.…”

Section: Minimal Concentration Requiredmentioning

confidence: 99%

Tyrosyl Motif in Amelogenins BindsN-Acetyl-d-glucosamine

Ravindranath

Moradian‐Oldak

Fincham

1999

Ameloblasts secrete amelogenins on the pre-existing enamel matrix glycoproteins at the dentine-enamel junction. The hypothesis that amelogenins may interact with enamel matrix glycoproteins is tested by hemagglutination of purified, native (porcine) and recombinant murine amelogenins (rM179 and rM166) and hemagglutination inhibition with sugars. Amelogenin agglutination of murine erythrocytes was specifically inhibited by N-acetylglucosamine ( 14 C]GlcNAc did indeed bind to this "amelogenin tyrosyl motif peptide" but not when the tyrosyl residues were substituted with phenylalanine or when the third proline was replaced by threonine. Significantly, this latter modification mimics a point mutation identified in a case of human X-linked amelogenesis imperfecta. The amelogenin tyrosyl motif peptide sequence showed a similarity to the secondary GlcNAc-binding site of wheat germ agglutinin.

“…Noncollagenous proteins comprise the secreted enamel organic matrix forming a scaffold, which begins to mineralize immediately after deposition (3). During and after the secretory stage, programmed and extensive proteolysis of the enamel proteins is associated with mineral crystal growth (4,5).…”

mentioning

confidence: 99%

Partial Rescue of the Amelogenin Null Dental Enamel Phenotype

Suggs

Wright

et al. 2008

The amelogenins are the most abundant secreted proteins in developing dental enamel. Enamel from amelogenin (Amelx) null mice is hypoplastic and disorganized, similar to that observed in X-linked forms of the human enamel defect amelogenesis imperfecta resulting from amelogenin gene mutations. Both transgenic strains that express the most abundant amelogenin (TgM180) have relatively normal enamel, but strains of mice that express a mutated amelogenin (TgP70T), which leads to amelogenesis imperfecta in humans, have heterogeneous enamel structures. When Amelx null (KO) mice were mated with transgenic mice that produce M180 (TgM180), the resultant TgM180KO offspring showed evidence of rescue in enamel thickness, mineral density, and volume in molar teeth. Rescue was not observed in the molars from the TgP70TKO mice. It was concluded that a single amelogenin protein was able to significantly rescue the KO phenotype and that one amino acid change abrogated this function during development.