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Journal of Dental Research Apr 2009Amelogenin and ameloblastin, the major enamel matrix proteins, are important for enamel mineralization. To identify their synergistic roles in enamel development, we...
Amelogenin and ameloblastin, the major enamel matrix proteins, are important for enamel mineralization. To identify their synergistic roles in enamel development, we generated Amel X(-/-)/Ambn(-/-) mice. These mice showed additional enamel defects in comparison with Amel X(-/-) or Ambn(-/-) mice. In 7-day-old Amel X(-/-)/Ambn(-/-) mice, not only was the ameloblast layer irregular and detached from the enamel surface, as in Ambn(-/-), but also, the enamel width was significantly reduced in the double-null mice as compared with Amel X(-/-) or Ambn(-/-) mice. Proteomic analysis of the double-null teeth revealed increased levels of RhoGDI (Arhgdia), a Rho-family-specific guanine nucleotide dissociation inhibitor, which is involved in important cellular processes, such as cell attachment. Both Amel X(-/-)/Ambn(-/-) mice and Ambn(-/-) mice displayed positive staining with RhoGDI antibody in the irregularly shaped ameloblasts detached from the matrix. Ameloblastin-regulated expression of RhoGDI suggests that Rho-mediated signaling pathway might play a role in enamel formation.
Topics: Amelogenesis; Amelogenin; Animals; Dental Enamel; Dental Enamel Proteins; Incisor; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Molar
PubMed: 19407150
DOI: 10.1177/0022034509334749 -
Journal of Materials Science. Materials... Aug 2021Caries and dental erosion are common oral diseases. Traditional treatments involve the mechanical removal of decay and filling but these methods are not suitable for... (Review)
Review
Caries and dental erosion are common oral diseases. Traditional treatments involve the mechanical removal of decay and filling but these methods are not suitable for cases involving large-scale enamel erosion, such as hypoplasia. To develop a noninvasive treatment, promoting remineralisation in the early stage of caries is of considerable clinical significance. Therefore, biomimetic mineralisation is an ideal approach for restoring enamel. Biomimetic mineralisation forms a new mineral layer that is tightly attached to the surface of the enamel. This review details the state-of-art achievements on the application of amelogenin and non-amelogenin, amorphous calcium phosphate, ions flow and other techniques in the biomimetic mineralisation of enamel. The ultimate goal of this review was to shed light on the requirements for enamel biomineralisation. Hence, herein, we summarise two strategies of biological minimisation systems for in situ enamel restoration inspired by amelogenesis that have been developed in recent years and compare their advantages and disadvantages.
Topics: Amelogenesis; Amelogenin; Animals; Biomimetic Materials; Biomimetics; Calcification, Physiologic; Calcium Phosphates; Dental Enamel; Dental Restoration, Permanent; Humans
PubMed: 34455518
DOI: 10.1007/s10856-021-06583-x -
Journal of Dental Research Dec 2021The nanofibrous nature and its intricate structural organization are the basis for the extraordinary ability of sound enamel to outlive masticatory forces at minimal... (Review)
Review
The nanofibrous nature and its intricate structural organization are the basis for the extraordinary ability of sound enamel to outlive masticatory forces at minimal failure rates. Apatite nanofibers of several hundreds of micrometers to possibly millimeters in length originate during the secretory stage of amelogenesis as 2-nm-thin and 15-nm-wide ribbons that develop and grow in length under the guidance of a dynamic mixture of specialized proteins, the developing enamel matrix (DEM). A critical role in the unidirectional and oriented growth of enamel mineral ribbons has been attributed to amelogenin, the major constituent of the DEM. This review elaborates on recent studies on the ability of ribbon-like assemblies of amelogenin to template the formation of an amorphous calcium phosphate precursor that transforms into apatite mineral ribbons similar to the ones observed in developing enamel. A mechanistic model of the biological processes that drive biomineralization in enamel is presented in the context of a comparative analysis of enamel mouse models and earlier structural data of the DEM emphasizing a regulatory role of the matrix metalloproteinase 20 in mineral deposition and the involvement of a process-directing agent for the templated mineral growth directed by amelogenin nanoribbons.
Topics: Amelogenesis; Amelogenin; Animals; Dental Enamel; Dental Enamel Proteins; Matrix Metalloproteinase 20; Mice; Nanotubes, Carbon
PubMed: 34009057
DOI: 10.1177/00220345211012925 -
Scientifica 2021Amelogenin is a common sex typing marker encountered in forensic case work. Phenotypically normal males have been reported in the literature who exhibit anomalous...
Amelogenin is a common sex typing marker encountered in forensic case work. Phenotypically normal males have been reported in the literature who exhibit anomalous amelogenin allele. These males express only a single amelogenin peak representing AMEL-X and are called as AMEL-Y-null males. Gender misclassification of such individuals is an obvious consequence of this mutation, as a male sample would falsely appear to be a female sample. This study was aimed to attribute the AMEL-Y-null male DNA profiles encountered in forensic casework in the Pakistani population to appropriate phylogenetic clade based on shared ancestry. A total of 18 null AMEL-Y males were screened out of the sample pool of 5000 male individuals, reflecting mutational frequency of 0.36%. A common phylogenetic ancestor is suggested for 17 individuals, based on computational analysis of the Y-STR haplotypes, shown to be belonging to the J haplogroup while only one sample belonged to the R group. The samples in J groups showed homology with subclades J2b2a M241 and J2b2a PH1648, while R group individual showed 100% homology with R1a. Data are reported after haplotype network development of AMEL-Y-null Pakistani males using Network 10.0 for the study of evolutionary distances and emergence of nodes.
PubMed: 34035976
DOI: 10.1155/2021/5521411 -
Frontiers in Physiology 2016
PubMed: 27667974
DOI: 10.3389/fphys.2016.00374 -
Fa Yi Xue Za Zhi Aug 2018To observe and analyse the allelic loss in parent-child identification cases, and to explore the type and mechanism of allelic loss as well as its influence on gender...
OBJECTIVES
To observe and analyse the allelic loss in parent-child identification cases, and to explore the type and mechanism of allelic loss as well as its influence on gender identification and solutions.
METHODS
After the detection by SiFaSTR™ 23plex DNA identification system, samples had the characteristics of the peak area of X was the same as the one of adjacent heterozygote or lower than one half of adjacent homozygote in females while X loss was observed in males were selected. X chromosome STR (X-STR) typing and X sequencing were performed. The samples with Y loss in males were confirmed by the detection of Y chromosome STR typing and sex-determining region of Y (SRY). The type and rate of allelic loss were confirmed and calculated, and the mechanism and influence of this variation were also analysed.
RESULTS
X allelic loss was observed in one male sample, the mutation in primer-binding region was confirmed by sequencing. The suspected X allelic loss was observed in four female samples, but the mutation in primer-binding region was confirmed by sequencing in only one sample. Y allelic loss was observed in seven male samples, SRY positive cases was detected in five of them, and two were SRY negative. Y-STR type was detected in four cases of the five SRY positive cases, which was not detected in the two SRY negative cases. The rate of allelic loss was about 0.029%.
CONCLUSIONS
X allelic loss does not affect the gender identification, but Y allelic loss may cause wrong gender identification. Thus, Y-STR or SRY should be detected for gender confirmation. When Y-STR genotypes are not detected in a "male" whose SRY detection is also negative, then the chromosome karyotype analysis and sex differentiation related genes test should be taken to further confirm the gender.
Topics: Amelogenin; DNA; Female; Humans; Loss of Heterozygosity; Male; Sex Determination Analysis
PubMed: 30465406
DOI: 10.12116/j.issn.1004-5619.2018.04.011 -
Cellular and Molecular Life Sciences :... Jan 2007Proteins of the developing enamel matrix include amelogenin, ameloblastin and enamelin. Of these three proteins amelogenin predominates. Protein-protein interactions are... (Comparative Study)
Comparative Study
Proteins of the developing enamel matrix include amelogenin, ameloblastin and enamelin. Of these three proteins amelogenin predominates. Protein-protein interactions are likely to occur at the ameloblast Tomes' processes between membrane-bound proteins and secreted enamel matrix proteins. Such protein-protein interactions could be associated with cell signaling or endocytosis. CD63 and Lamp1 are ubiquitously expressed, are lysosomal integral membrane proteins, and localize to the plasma membrane. CD63 and Lamp1 interact with amelogenin in vitro. In this study our objective was to study the molecular events of intercellular trafficking of an exogenous source of amelogenin, and related this movement to the spatiotemporal expression of CD63 and Lamp1 using various cell lineages. Exogenously added amelogenin moves rapidly into the cell into established Lamp1-positive vesicles that subsequently localize to the perinuclear region. These data indicate a possible mechanism by which amelogenin, or degraded amelogenin peptides, are removed from the extracellular matrix during enamel formation and maturation.
Topics: Amelogenesis; Amelogenin; Animals; Antigens, CD; Biological Transport; Cell Line; DNA Primers; Dogs; Fluorescent Antibody Technique; Genetic Vectors; Green Fluorescent Proteins; Humans; Immunohistochemistry; Lysosomal-Associated Membrane Protein 1; Mice; Platelet Membrane Glycoproteins; Reverse Transcriptase Polymerase Chain Reaction; Tetraspanin 30; Transport Vesicles
PubMed: 17187173
DOI: 10.1007/s00018-006-6429-4 -
Proceedings of the National Academy of... Aug 2020As the hardest tissue formed by vertebrates, enamel represents nature's engineering masterpiece with complex organizations of fibrous apatite crystals at the nanometer...
As the hardest tissue formed by vertebrates, enamel represents nature's engineering masterpiece with complex organizations of fibrous apatite crystals at the nanometer scale. Supramolecular assemblies of enamel matrix proteins (EMPs) play a key role as the structural scaffolds for regulating mineral morphology during enamel development. However, to achieve maximum tissue hardness, most organic content in enamel is digested and removed at the maturation stage, and thus knowledge of a structural protein template that could guide enamel mineralization is limited at this date. Herein, by examining a gene-modified mouse that lacked enzymatic degradation of EMPs, we demonstrate the presence of protein nanoribbons as the structural scaffolds in developing enamel matrix. Using in vitro mineralization assays we showed that both recombinant and enamel-tissue-based amelogenin nanoribbons are capable of guiding fibrous apatite nanocrystal formation. In accordance with our understanding of the natural process of enamel formation, templated crystal growth was achieved by interaction of amelogenin scaffolds with acidic macromolecules that facilitate the formation of an amorphous calcium phosphate precursor which gradually transforms into oriented apatite fibers along the protein nanoribbons. Furthermore, this study elucidated that matrix metalloproteinase-20 is a critical regulator of the enamel mineralization as only a recombinant analog of a MMP20-cleavage product of amelogenin was capable of guiding apatite mineralization. This study highlights that supramolecular assembly of the scaffold protein, its enzymatic processing, and its ability to interact with acidic carrier proteins are critical steps for proper enamel development.
Topics: Amelogenesis; Amelogenin; Animals; Apatites; Dental Enamel; Dental Enamel Proteins; Mice; Nanofibers
PubMed: 32737162
DOI: 10.1073/pnas.2007838117 -
Journal of Structural Biology Jun 2022Amelogenin, the most abundant enamel matrix protein, plays several critical roles in enamel formation. Importantly, we previously found that the singular phosphorylation...
Amelogenin, the most abundant enamel matrix protein, plays several critical roles in enamel formation. Importantly, we previously found that the singular phosphorylation site at Ser16 in amelogenin plays an essential role in amelogenesis. Studies of genetically knock-in (KI) modified mice in which Ser16 in amelogenin is substituted with Ala that prevents amelogenin phosphorylation, and in vitro mineralization experiments, have shown that phosphorylated amelogenin transiently stabilizes amorphous calcium phosphate (ACP), the initial mineral phase in forming enamel. Furthermore, KI mice exhibit dramatic differences in the enamel structure compared with wild type (WT) mice, including thinner enamel lacking enamel rods and ectopic surface calcifications. Here, we now demonstrate that amelogenin phosphorylation also affects the organization and composition of mature enamel mineral. We compared WT, KI, and heterozygous (HET) enamel and found that in the WT elongated crystals are co-oriented within each rod, however, their c-axes are not aligned with the rods' axes. In contrast, in rod-less KI enamel, crystalline c-axes are less co-oriented, with misorientation progressively increasing toward the enamel surface, which contains spherulites, with a morphology consistent with abiotic formation. Furthermore, we found significant differences in enamel hardness and carbonate content between the genotypes. ACP was also observed in the interrod of WT and HET enamel, and throughout aprismatic KI enamel. In conclusion, amelogenin phosphorylation plays crucial roles in controlling structural, crystallographic, mechanical, and compositional characteristics of dental enamel. Thus, loss of amelogenin phosphorylation leads to a reduction in the biological control over the enamel mineralization process.
Topics: Amelogenesis; Amelogenin; Animals; Dental Enamel Proteins; Ions; Mice; Minerals; Phosphorylation
PubMed: 35219810
DOI: 10.1016/j.jsb.2022.107844 -
Monographs in Oral Science 2011Dental fluorosis occurs as a result of excess fluoride ingestion during tooth formation. Enamel fluorosis and primary dentin fluorosis can only occur when teeth are... (Review)
Review
Dental fluorosis occurs as a result of excess fluoride ingestion during tooth formation. Enamel fluorosis and primary dentin fluorosis can only occur when teeth are forming, and therefore fluoride exposure (as it relates to dental fluorosis) occurs during childhood. In the permanent dentition, this would begin with the lower incisors, which complete mineralization at approximately 2-3 years of age, and end after mineralization of the third molars. The white opaque appearance of fluorosed enamel is caused by a hypomineralized enamel subsurface. With more severe dental fluorosis, pitting and a loss of the enamel surface occurs, leading to secondary staining (appearing as a brown color). Many of the changes caused by fluoride are related to cell/matrix interactions as the teeth are forming. At the early maturation stage, the relative quantity of amelogenin protein is increased in fluorosed enamel in a dose-related manner. This appears to result from a delay in the removal of amelogenins as the enamel matures. In vitro, when fluoride is incorporated into the mineral, more protein binds to the forming mineral, and protein removal by proteinases is delayed. This suggests that altered protein/mineral interactions are in part responsible for retention of amelogenins and the resultant hypomineralization that occurs in fluorosed enamel. Fluoride also appears to enhance mineral precipitation in forming teeth, resulting in hypermineralized bands of enamel, which are then followed by hypomineralized bands. Enhanced mineral precipitation with local increases in matrix acidity may affect maturation stage ameloblast modulation, potentially explaining the dose-related decrease in cycles of ameloblast modulation from ruffle-ended to smooth-ended cells that occur with fluoride exposure in rodents. Specific cellular effects of fluoride have been implicated, but more research is needed to determine which of these changes are relevant to the formation of fluorosed teeth. As further studies are done, we will better understand the mechanisms responsible for dental fluorosis.
Topics: Ameloblasts; Amelogenesis; Amelogenin; Cariostatic Agents; Chronic Disease; Dental Enamel; Fluorides; Fluorosis, Dental; Humans; Odontogenesis; Tooth Calcification; Tooth Demineralization
PubMed: 21701193
DOI: 10.1159/000327028