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Journal of Dental Research Jan 2024Dental enamel formation is coordinated by ameloblast differentiation, production of enamel matrix proteins, and crystal growth. The factors regulating ameloblast...
Dental enamel formation is coordinated by ameloblast differentiation, production of enamel matrix proteins, and crystal growth. The factors regulating ameloblast differentiation are not fully understood. Here we show that the high mobility group N (HMGN) nucleosomal binding proteins modulate the rate of ameloblast differentiation and enamel formation. We found that HMGN1 and HMGN2 proteins are downregulated during mouse ameloblast differentiation. Genetically altered mice lacking HMGN1 and HMGN2 proteins show faster ameloblast differentiation and a higher rate of enamel deposition in mice molars and incisors. In vitro differentiation of induced pluripotent stem cells to dental epithelium cells showed that HMGN proteins modulate the expression and chromatin accessibility of ameloblast-specific genes and affect the binding of transcription factors epiprofin and PITX2 to ameloblast-specific genes. Our results suggest that HMGN proteins regulate ameloblast differentiation and enamel mineralization by modulating lineage-specific chromatin accessibility and transcription factor binding to ameloblast regulatory sites.
Topics: Animals; Mice; Ameloblasts; HMGN2 Protein; HMGN1 Protein; Epigenesis, Genetic; Cell Differentiation; HMGN Proteins; Transcription Factors; Dental Enamel Proteins; Chromatin; Amelogenin
PubMed: 37950483
DOI: 10.1177/00220345231202468 -
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 -
Ecotoxicology and Environmental Safety Oct 2022Sulphur dioxide (SO) and fluoride are among the most common environmental pollutants affecting human health, and both co-exist in areas predominantly consuming coal. It...
Sulphur dioxide (SO) and fluoride are among the most common environmental pollutants affecting human health, and both co-exist in areas predominantly consuming coal. It is vital to analyse the combined toxicity of SO and fluoride, and their effects on health and the underlying mechanisms of their co-exposure have not yet been adequately assessed. In the present study, we used ICR mice and LS8 cells to investigate the toxicity of SO and fluoride exposure to the enamel, alone or in combination. Factorial design analysis was used to reveal the combined toxicity in vitro and in vivo. Co-exposure to SO and fluoride exacerbated enamel injury, resulting in more severe hypomineralization of incisor, and enamel structure disorders in mice, and could induce the accumulation of protein residue in the matrix of the enamel. Amelogenin expression was increased upon exposure to SO and fluoride, but enamel matrix proteases were not affected. Consistent with our in vivo results, co-exposure of SO and fluoride aggravated amelogenin expression in LS8 cells, and increased the YAP and RUNX2 levels. Co-exposure to SO and fluoride resulted in greater toxicity than individual exposure, both in vitro and in vivo, indicating that residents of areas exposed to SO and fluoride may have an increased risk of developing enamel damage.
Topics: Amelogenin; Animals; Coal; Core Binding Factor Alpha 1 Subunit; Environmental Pollutants; Fluorides; Humans; Incisor; Mice; Mice, Inbred ICR; Peptide Hydrolases; Signal Transduction; Sulfur Dioxide; Up-Regulation; YAP-Signaling Proteins
PubMed: 36155332
DOI: 10.1016/j.ecoenv.2022.114106 -
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 -
Legal Medicine (Tokyo, Japan) Sep 2021In this study, we located eight samples with null alleles of amelogenin out of 10,750 cases, and discussed the influence in gender identification and forensic personal...
In this study, we located eight samples with null alleles of amelogenin out of 10,750 cases, and discussed the influence in gender identification and forensic personal identification. Amelogenin was detected and retested by several autosomal STR kits and sex chromosomal STR kits, and the causes were analyzed by chromosome karyotype analysis and Y chromosome microdeletion detection if necessary. Suspected AMEL-X loss was observed in five samples, but no abnormality was detected in the X-STR loci. AMEL-X was recovered when samples were retested by other detection systems designed with different primers. One sample had AMEL-X and X-STR loci loss, and the karyotype was chimeric 45,X0[70]/46,X,+mar[13].Two male samples lost AMEL-Y fragment, and both of them lost DYS522-DYS570-DYS576 loci, but no abnormalities were found in the STS loci of SRY and AZF regions. Therefore, when carrying out gender identification by using amelogenin, it is essential to focus on null alleles of amelogenin. In especially, deal with the samples collected from the individuals who had chromosomal hereditary disorders(e.g. Turner Syndrome and Oligospermia / Azoospermia). In order to achieve this, laboratories should have various techniques to verify the null alleles of amelogenin and ensure accurate genotyping. Accurate genotyping of amelogenin and DNA database establishment are vital for personal identification.
Topics: Alleles; Amelogenin; Chromosomes, Human, Y; DNA Primers; Humans; Male
PubMed: 34052679
DOI: 10.1016/j.legalmed.2021.101899 -
Journal of Materials Chemistry. B Mar 2020The regenerative materials for hard tissues, i.e. tooth (enamel, dentin, and cementum) and bone, require extremely high standards in terms of their mechanical... (Review)
Review
The regenerative materials for hard tissues, i.e. tooth (enamel, dentin, and cementum) and bone, require extremely high standards in terms of their mechanical properties, biocompatibility, bioactivity, and multiple-functionality. Among them, the biomedical materials inspired from various natural proteins have attracted increasing research attention. These blueprint proteins include various hard-tissue-related proteins, such as collagen and non-collagenous proteins (e.g. amelogenin, dentin phosphoprotein, bone sialoprotein, and osteopontin), as well as other natural proteins like mussel foot proteins. The current review highlights the structure-function relationship of protein bioinspired biomedical materials (e.g. polymers and polypeptides) and their applications for tooth and bone regeneration. Specifically, the materials bioinspired from salivary acquired pellicle proteins, which have a strong affinity to hydroxyapatite surfaces, are discussed in detail. Finally, the challenges associated with these protein bioinspired materials and their industrialization potentials are discussed.
Topics: Amelogenin; Animals; Biocompatible Materials; Biological Products; Bone and Bones; Collagen; Durapatite; Extracellular Matrix Proteins; Humans; Integrin-Binding Sialoprotein; Mechanical Phenomena; Nanostructures; Osteopontin; Phosphoproteins; Polymers; Proteins; Regeneration; Sialoglycoproteins; Tissue Engineering; Tissue Scaffolds; Tooth
PubMed: 32091067
DOI: 10.1039/d0tb00139b -
Journal of Forensic Dental Sciences 2018Forensic odontology is the application of dental principles to legal issues. It is an investigative aspect of dentistry that analyzes dental evidence for human... (Review)
Review
Forensic odontology is the application of dental principles to legal issues. It is an investigative aspect of dentistry that analyzes dental evidence for human identification. Sex determination is a subdivision of forensic odontology, and it is important especially when information relating to the deceased is unavailable. Sex determination becomes the first priority in the process of identification of a person by a forensic investigator in the case of mishaps, chemical and nuclear bomb explosions, natural disasters, crime investigations, and ethnic studies. Determination of sex/gender using skeletal remains presents a great problem to forensic experts, especially when only fragments of body are recovered. Forensic odontologist can assist other experts to determine the sex of the remains using teeth and skull traits. Various features of teeth such as morphology, crown size, and root length are characteristics for male and female sexes. There are also differences in the skull pattern and skull traits of two sexes. These will help forensic odontologists to identify the sex of the remains. The library dissertation contents and several articles and books were electronically searched in Google using the keywords "sex determination," "forensic dentistry," "sex determination in forensic dentistry." The contents were screened between 1950 and 2015 by going through the title and abstracts and full-text reading. The purpose of this article is to familiarize the different methods of sex determination.
PubMed: 30745778
DOI: 10.4103/jfo.jfds_55_17 -
Materials Today. Advances Jun 2023Organic macromolecules exert remarkable control over the nucleation and growth of inorganic crystallites during (bio)mineralization, as exemplified during enamel...
Organic macromolecules exert remarkable control over the nucleation and growth of inorganic crystallites during (bio)mineralization, as exemplified during enamel formation where the protein amelogenin regulates the formation of hydroxyapatite (HAP). However, it is poorly understood how fundamental processes at the organic-inorganic interface, such as protein adsorption and/or incorporation into minerals, regulates nucleation and crystal growth due to technical challenges in observing and characterizing mineral-bound organics at high-resolution. Here, atom probe tomography techniques were developed and applied to characterize amelogenin-mineralized HAP particles , revealing distinct organic-inorganic interfacial structures and processes at the nanoscale. Specifically, visualization of amelogenin across the mineralized particulate demonstrates protein can become entrapped during HAP crystal aggregation and fusion. Identification of protein signatures and structural interpretations were further supported by standards analyses, i.e., defined HAP surfaces with and without amelogenin adsorbed. These findings represent a significant advance in the characterization of interfacial structures and, more so, interpretation of fundamental organic-inorganic processes and mechanisms influencing crystal growth. Ultimately, this approach can be broadly applied to inform how potentially unique and diverse organic-inorganic interactions at different stages regulates the growth and evolution of various biominerals.
PubMed: 37324279
DOI: 10.1016/j.mtadv.2023.100378 -
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