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Journal of Dental Research Sep 2021Biomineralization of enamel, dentin, and bone involves the deposition of apatite mineral crystals within an organic matrix. Bone and teeth are classic examples of... (Review)
Review
Biomineralization of enamel, dentin, and bone involves the deposition of apatite mineral crystals within an organic matrix. Bone and teeth are classic examples of biomaterials with unique biomechanical properties that are crucial to their function. The collagen-based apatite mineralization and the important function of noncollagenous proteins are similar in dentin and bone; however, enamel is formed in a unique amelogenin-containing protein matrix. While the structure and organic composition of enamel are different from those of dentin and bone, the principal molecular mechanisms of protein-protein interactions, protein self-assembly, and control of crystallization events by the organic matrix are common among these apatite-containing tissues. This review briefly summarizes enamel and dentin matrix components and their interactions with other extracellular matrix components and calcium ions in mediating the mineralization process. We highlight the crystallization events that are controlled by the protein matrix and their interactions in the extracellular matrix during enamel and dentin biomineralization. Strategies for peptide-inspired biomimetic growth of tooth enamel and bioinspired mineralization of collagen to stimulate repair of demineralized dentin and bone tissue engineering are also addressed.
Topics: Amelogenin; Biomineralization; Collagen; Dental Enamel; Dentin
PubMed: 34151644
DOI: 10.1177/00220345211018405 -
Orphanet Journal of Rare Diseases Apr 2007Amelogenesis imperfecta (AI) represents a group of developmental conditions, genomic in origin, which affect the structure and clinical appearance of enamel of all or... (Review)
Review
Amelogenesis imperfecta (AI) represents a group of developmental conditions, genomic in origin, which affect the structure and clinical appearance of enamel of all or nearly all the teeth in a more or less equal manner, and which may be associated with morphologic or biochemical changes elsewhere in the body. The prevalence varies from 1:700 to 1:14,000, according to the populations studied. The enamel may be hypoplastic, hypomineralised or both and teeth affected may be discoloured, sensitive or prone to disintegration. AI exists in isolation or associated with other abnormalities in syndromes. It may show autosomal dominant, autosomal recessive, sex-linked and sporadic inheritance patterns. In families with an X-linked form it has been shown that the disorder may result from mutations in the amelogenin gene, AMELX. The enamelin gene, ENAM, is implicated in the pathogenesis of the dominant forms of AI. Autosomal recessive AI has been reported in families with known consanguinity. Diagnosis is based on the family history, pedigree plotting and meticulous clinical observation. Genetic diagnosis is presently only a research tool. The condition presents problems of socialisation, function and discomfort but may be managed by early vigorous intervention, both preventively and restoratively, with treatment continued throughout childhood and into adult life. In infancy, the primary dentition may be protected by the use of preformed metal crowns on posterior teeth. The longer-term care involves either crowns or, more frequently these days, adhesive, plastic restorations.
Topics: Adolescent; Adult; Amelogenesis Imperfecta; Amelogenin; Child; Child, Preschool; Dental Enamel; Dental Enamel Proteins; Diagnosis, Differential; Genetic Diseases, X-Linked; Humans; Infant; Kallikreins; Matrix Metalloproteinase 20; Mutation; Syndrome
PubMed: 17408482
DOI: 10.1186/1750-1172-2-17 -
International Journal of Oral Science Jan 2019Tooth enamel is a complex mineralized tissue consisting of long and parallel apatite crystals configured into decussating enamel rods. In recent years, multiple... (Review)
Review
Tooth enamel is a complex mineralized tissue consisting of long and parallel apatite crystals configured into decussating enamel rods. In recent years, multiple approaches have been introduced to generate or regenerate this highly attractive biomaterial characterized by great mechanical strength paired with relative resilience and tissue compatibility. In the present review, we discuss five pathways toward enamel tissue engineering, (i) enamel synthesis using physico-chemical means, (ii) protein matrix-guided enamel crystal growth, (iii) enamel surface remineralization, (iv) cell-based enamel engineering, and (v) biological enamel regeneration based on de novo induction of tooth morphogenesis. So far, physical synthesis approaches using extreme environmental conditions such as pH, heat and pressure have resulted in the formation of enamel-like crystal assemblies. Biochemical methods relying on enamel proteins as templating matrices have aided the growth of elongated calcium phosphate crystals. To illustrate the validity of this biochemical approach we have successfully grown enamel-like apatite crystals organized into decussating enamel rods using an organic enamel protein matrix. Other studies reviewed here have employed amelogenin-derived peptides or self-assembling dendrimers to re-mineralize mineral-depleted white lesions on tooth surfaces. So far, cell-based enamel tissue engineering has been hampered by the limitations of presently existing ameloblast cell lines. Going forward, these limitations may be overcome by new cell culture technologies. Finally, whole-tooth regeneration through reactivation of the signaling pathways triggered during natural enamel development represents a biological avenue toward faithful enamel regeneration. In the present review we have summarized the state of the art in enamel tissue engineering and provided novel insights into future opportunities to regenerate this arguably most fascinating of all dental tissues.
Topics: Acid Etching, Dental; Amelogenin; Biomimetics; Dental Enamel; Dental Enamel Proteins; Dentistry; Tissue Engineering; Tooth Remineralization
PubMed: 30610185
DOI: 10.1038/s41368-018-0038-6 -
Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi... Aug 2021To investigate the dynamic process of the self-assembly behaviors of a full-length human amelogenin (AM) and its functional fragments tyrosine-rich amelogenin peptide...
OBJECTIVES
To investigate the dynamic process of the self-assembly behaviors of a full-length human amelogenin (AM) and its functional fragments tyrosine-rich amelogenin peptide (TRAP) and leucine-rich amelogenin peptide(LRAP) and its role in hydroxyapatite (HA) crystal formation.
METHODS
The full-length human AM and its functional fragments, TRAP and LRAP, were reassembled and purified . The protein solution of 100 µg‧mL, pH=8, was prepared in Tris-HCl and incubated at room temperature for 1-15 min. Their self-assembly behaviors were observed and compared under a transmission electron microscope (TEM). The full-length AM was added to artificial saliva and incubated for 3 days. A scanning electron microscope (SEM) was used in observing the morphology of the induced new crystals. Then, TARP and LRAP were added. The resulting solution was incubated for 3 days and then observed again.
RESULTS
When pH=8, the full-length human AM and TRAP assembly started spontaneously and formed "nanospheres" after 15 min.The nanospheres formed by TRAP existed independently, with a uniform size but without obvious internal structures. The full-length AM was assembled hierarchically, which formed "nanospheres" and further extended in all directions, formed a chain structure, and then aggregated into a net. The self-assembly behavior of LRAP was not obvious. Proteins mostly existed in the form of monomers without "nanosphere" formation. Only few oligomers were observed. The full-length AM was induced independently for 3 days to form rod-shaped HA crystals. TRAP and LRAP proteins were added, after 3 days the crystal elongation was obvious in the c axis, but the growth in plane A and plane B was poor.
CONCLUSIONS
The self-assembly and mineralization behaviors of full-length human AM, TRAP, and LRAP were consistent with the directional growth mechanism of HA crystals , providing a theoretical basis for the role of the fragments in the growth and maturation of HA crystals.
Topics: Amelogenin; Dental Enamel Proteins; Durapatite; Humans
PubMed: 34409797
DOI: 10.7518/hxkq.2021.04.007 -
Journal of Materials Chemistry. B 2015Mature tooth enamel is acellular and does not regenerate itself. Developing technologies that rebuild tooth enamel and preserve tooth structure is therefore of great...
Mature tooth enamel is acellular and does not regenerate itself. Developing technologies that rebuild tooth enamel and preserve tooth structure is therefore of great interest. Considering the importance of amelogenin protein in dental enamel formation, its ability to control apatite mineralization , and its potential to be applied in fabrication of future bio-inspired dental material this review focuses on two major subjects: amelogenin and enamel biomimetics. We review the most recent findings on amelogenin secondary and tertiary structural properties with a focus on its interactions with different targets including other enamel proteins, apatite mineral, and phospholipids. Following a brief overview of enamel hierarchical structure and its mechanical properties we will present the state-of-the-art strategies in the biomimetic reconstruction of human enamel.
PubMed: 26251723
DOI: 10.1039/C5TB00163C -
Frontiers in Physiology 2022Enamel research experienced an unprecedented period of growth during the latter part of the 20th century until today. This growth is in part due to the contributions of... (Review)
Review
Enamel research experienced an unprecedented period of growth during the latter part of the 20th century until today. This growth is in part due to the contributions of a number of iconic scientists such as Alan G. Fincham, the focus of the present review. Alan was involved in many of the seminal discoveries of this time, including the identification of the critical amelogenin peptides TRAP and LRAP, the determination of the amelogenin amino acid sequence, the identification of the sole serin-16 phosphorylation site, and the amelogenin nanosphere theory. Alan was also a superb mentor to graduate students and others. His experience and leadership related to problem-based learning greatly affected predoctoral dental education at the University of Southern California and in the United States.
PubMed: 36545279
DOI: 10.3389/fphys.2022.1071265 -
Frontiers in Bioscience (Landmark... Jun 2012Enamel is a hard nanocomposite bioceramic with significant resilience that protects the mammalian tooth from external physical and chemical damages. The remarkable... (Review)
Review
Enamel is a hard nanocomposite bioceramic with significant resilience that protects the mammalian tooth from external physical and chemical damages. The remarkable mechanical properties of enamel are associated with its hierarchical structural organization and its thorough connection with underlying dentin. This dynamic mineralizing system offers scientists a wealth of information that allows the study of basic principels of organic matrix-mediated biomineralization and can potentially be utilized in the fields of material science and engineering for development and design of biomimetic materials. This chapter will provide a brief overview of enamel hierarchical structure and properties and the process and stages of amelogenesis. Particular emphasis is given to current knowledge of extracellular matrix protein and proteinases, and the structural chemistry of the matrix components and their putative functions. The chapter will conclude by discussing the potential of enamel for regrowth.
Topics: Amelogenesis Imperfecta; Amelogenin; Animals; Biomimetic Materials; Dental Enamel; Dental Enamel Proteins; Dental Materials; Extracellular Matrix Proteins; Humans; Hydrogen-Ion Concentration; Minerals; Peptide Hydrolases; Protein Multimerization; Tooth Calcification
PubMed: 22652761
DOI: 10.2741/4034 -
Journal of Structural Biology Dec 2021During enamel formation, the organic enamel protein matrix interacts with calcium phosphate minerals to form elongated, parallel, and bundled enamel apatite crystals of... (Review)
Review
During enamel formation, the organic enamel protein matrix interacts with calcium phosphate minerals to form elongated, parallel, and bundled enamel apatite crystals of extraordinary hardness and biomechanical resilience. The enamel protein matrix consists of unique enamel proteins such as amelogenin, ameloblastin, and enamelin, which are secreted by highly specialized cells called ameloblasts. The ameloblasts also facilitate calcium and phosphate ion transport toward the enamel layer. Within ameloblasts, enamel proteins are transported as a polygonal matrix with 5 nm subunits in secretory vesicles. Upon expulsion from the ameloblasts, the enamel protein matrix is re-organized into 20 nm subunit compartments. Enamel matrix subunit compartment assembly and expansion coincide with C-terminal cleavage by the MMP20 enamel protease and N-terminal amelogenin self-assembly. Upon enamel crystal precipitation, the enamel protein phase is reconfigured to surround the elongating enamel crystals and facilitate their elongation in C-axis direction. At this stage of development, and upon further amelogenin cleavage, central and polyproline-rich fragments of the amelogenin molecule associate with the growing mineral crystals through a process termed "shedding", while hexagonal apatite crystals fuse in longitudinal direction. Enamel protein sheath-coated enamel "dahlite" crystals continue to elongate until a dense bundle of parallel apatite crystals is formed, while the enamel matrix is continuously degraded by proteolytic enzymes. Together, these insights portrait enamel mineral nucleation and growth as a complex and dynamic set of interactions between enamel proteins and mineral ions that facilitate regularly seeded apatite growth and parallel enamel crystal elongation.
Topics: Ameloblasts; Amelogenesis; Amelogenin; Animals; Apatites; Calcium; Calcium Phosphates; Crystallization; Dental Enamel; Dental Enamel Proteins; Humans; Microscopy, Electron; Minerals
PubMed: 34748943
DOI: 10.1016/j.jsb.2021.107809 -
Frontiers in Physiology 2022Phosphorylation of serine residues has been recognized as a pivotal event in the evolution of mineralized tissues in many biological systems. During enamel development,...
Phosphorylation of serine residues has been recognized as a pivotal event in the evolution of mineralized tissues in many biological systems. During enamel development, the extracellular matrix protein amelogenin is most abundant and appears to be critical to the extreme high aspect ratios (length:width) of apatite mineral fibers reaching several millimeters in larger mammalian teeth. A 14-residue peptide (14P2, residues Gly8 to Thr21) was previously identified as a key sequence mediating amelogenin assembly formation, the domain also contains the native single phosphoserine residue (Ser16) of the full-length amelogenin. In this research, 14P2 and its phosphorylated form (p14P2) were investigated at pH 6.0 with various calcium and phosphate ion concentrations, indicating that both peptides could self-assemble into amyloid-like conformation but with differences in structural details. With calcium, the distance between P within the p14P2 self-assemblies is averaged to be 4.4 ± 0.2Å, determined by solid-state NMR P PITHIRDS-CT experiments. Combining with other experimental results, solid-state Nuclear Magnetic Resonance (SSNMR) suggests that the p14P2 self-assemblies are in parallel in-register -sheet conformation and divalent calcium ions most likely connect two adjacent peptide chains by binding to the phosphate group of Ser16 and the carboxylate of Glu18 side-chain. This study on the interactions between calcium ions and amelogenin-derived peptides provides insights on how amelogenin may self-assemble in the presence of calcium ions in early enamel development.
PubMed: 36589425
DOI: 10.3389/fphys.2022.1063970 -
The International Journal of... Feb 1995Amelogenin is a major protein constituent of the developing enamel matrix. This protein is now well characterized from the data of amino acid sequences which have been... (Review)
Review
Amelogenin is a major protein constituent of the developing enamel matrix. This protein is now well characterized from the data of amino acid sequences which have been shown to be at a high degree of homology between all species investigated to date. The gene structure of this protein has been demonstrated and it is confirmed that there are two amelogenin genes, one on the X-chromosome and the other on the Y-chromosome in humans. The mapping of human amelogenin gene in the p22 region on the X-chromosome and the gene on the Y-chromosome was established. It has been confirmed that several types of X-linked amelogenesis imperfecta are caused by structural defects in the amelogenin gene on the X-chromosome. The physiological importance of amelogenin in the enamel formation is suggested by the symptoms of this inherited disease in addition to inhibition experiments of amelogenin transcription and translation (Couwenhoven et al., J. Craniofac. Genet. Dev. Biol. 13:259-269, 1993; Diekwisch et al., Development 117:471-482, 1993). Recently, an attempt to synthesize recombinant mouse amelogenin by E. coli was also undertaken (Simmer et al., Calcif. Tissue Int. 54:312-319, 1994). The regulation of amelogenin expression is now under investigation (Chen et al., Dev. Dynamics 199:189-198, 1994) and the elucidation of this mechanism will contribute a great deal to the study of tooth development.
Topics: Alternative Splicing; Amelogenin; Animals; Base Sequence; Biological Evolution; Chromosome Mapping; DNA; Dental Enamel Proteins; Humans; Molecular Sequence Data; RNA, Messenger; X Chromosome; Y Chromosome
PubMed: 7626398
DOI: No ID Found