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Frontiers in Endocrinology 2021Most cells use calcium (Ca) as a second messenger to convey signals that affect a multitude of biological processes. The ability of Ca to bind to proteins to alter their... (Review)
Review
Most cells use calcium (Ca) as a second messenger to convey signals that affect a multitude of biological processes. The ability of Ca to bind to proteins to alter their charge and conformation is essential to achieve its signaling role. Cytosolic Ca (Ca) concentration is maintained low at ~100 nM so that the impact of elevations in Ca is readily sensed and transduced by cells. However, such elevations in Ca must be transient to prevent detrimental effects. Cells have developed a variety of systems to rapidly clear the excess of Ca including Ca pumps, exchangers and sequestering Ca within intracellular organelles. This Ca signaling toolkit is evolutionarily adapted so that each cell, tissue, and organ can fulfill its biological function optimally. One of the most specialized cells in mammals are the enamel forming cells, the ameloblasts, which also handle large quantities of Ca. The end goal of ameloblasts is to synthesize, secrete and mineralize a unique proteinaceous matrix without the benefit of remodeling or repair mechanisms. Ca uptake into ameloblasts is mainly regulated by the store operated Ca entry (SOCE) before it is transported across the polarized ameloblasts to reach the insulated enamel space. Here we review the ameloblasts Ca signaling toolkit and address how the common electronegative non-metal fluoride can alter its function, potentially addressing the biology of dental fluorosis.
Topics: Ameloblasts; Animals; Calcification, Physiologic; Calcium; Dental Sac; Epithelial Cells; Fluorides; Humans
PubMed: 34456880
DOI: 10.3389/fendo.2021.730913 -
Journal of Dental Research Apr 2020Amelogenesis imperfecta (AI) is a collection of genetic disorders affecting the quality and/or quantity of tooth enamel. More than 20 genes are, so far, known to be...
Amelogenesis imperfecta (AI) is a collection of genetic disorders affecting the quality and/or quantity of tooth enamel. More than 20 genes are, so far, known to be responsible for this condition. In this study, we recruited 3 Turkish families with hypomaturation AI. Whole-exome sequence analyses identified disease-causing mutations in each proband, and these mutations cosegregated with the AI phenotype in all recruited members of each family. The AI-causing mutations in family 1 were a novel mutation [NM_182680.1:c.143T>C, p.(Leu48Ser)] in the proband and a novel homozygous mutation [NM_004771.3:c.616G>A, p.(Asp206Asn)] in the mother of the proband. Previously reported compound heterozygous mutations [NM_004771.3:c.103A>C, p.(Arg35=) and c.389C>T, p.(Thr130Ile)] caused the AI in family 2 and family 3. Minigene splicing analyses revealed that the missense mutation increased exonic definition of exon 4 and the synonymous mutation decreased exonic definition of exon 1. These mutations would trigger an alteration of exon usage during RNA splicing, causing the enamel malformations. These results broaden our understanding of molecular genetic pathology of tooth enamel formation.
Topics: Amelogenesis Imperfecta; Dental Enamel; Exons; Humans; Mutation; Pedigree
PubMed: 31999931
DOI: 10.1177/0022034520901708 -
European Archives of Paediatric... Dec 2022Amelogenesis imperfecta (AI) is a hereditary condition which affects the composition and structure of enamel in terms of hypoplasia and/or hypomineralization. The...
PURPOSE
Amelogenesis imperfecta (AI) is a hereditary condition which affects the composition and structure of enamel in terms of hypoplasia and/or hypomineralization. The condition severely affects patients facing such difficulties as hypersensibility, loss of tooth substance and poor aesthetics. The objective is to perform a systematic review of patient-reported outcome measures (PROMs) in patients with amelogenesis imperfecta.
METHODS
Inclusion criteria were articles written in English, including PROMs from patients with amelogenesis imperfecta. The databases PubMed, Scopus and Web of Science were searched on April 27, 2022, and eligible articles were screened. Exclusion criteria were articles based on proxy reports and single case reports.
RESULTS
405 studies were screened in terms of title and abstract, with 31 articles eligible for full-text screening, resulting in a total of 11 articles eligible for inclusion, (articles including 4-82 patients). The content was analyzed, resulting in the outcome divided into seven domains: Oral Health-Related Quality of Life (OHRQoL), Dental fear, Esthetics, Psychosocial factors, Function, Dental hypersensitivity, and Treatment outcome.
CONCLUSION
The limited quantity of research on PROMS from patients with AI indicates a significant impact of OHRQoL and daily life. A large variety of approaches have been presented in the articles. Patients report concerns of esthetics, hypersensitivity, function, and a general impact on well-being and social interaction. This highlights the importance for the need of early dental treatment.
PROSPERO REGISTRATION NUMBER
256875.
Topics: Humans; Amelogenesis Imperfecta; Quality of Life; Dental Enamel; Patient Reported Outcome Measures
PubMed: 35896941
DOI: 10.1007/s40368-022-00737-3 -
The Saudi Dental Journal Jul 2022This work aimed to study the rate and quality of maturation of the mineral component of retained teeth 3.8, 4.8 and lower jaw fragment of a human in connective tissue...
PURPOSE
This work aimed to study the rate and quality of maturation of the mineral component of retained teeth 3.8, 4.8 and lower jaw fragment of a human in connective tissue dysplasia in different periods of postpartum ontogenesis.
METHODS
The study involved 102 men (76 with connective tissue dysplasia and 26 without connective tissue dysplasia) divided into groups by age: 31-40, 41-50, 51-60 years. One tooth 3.8, 4.8 and a fragment of the alveolar part of the lower jaw in the projection of teeth 3.8, 4.8 0.5*0.5 cm in size were extracted from each examinee for medical indications.
RESULTS
Low optical density values are observed at the age of 41-50 years, at the age of 51-60 years, indicating decreased mineral density and the presence of total areas of hypomineralization from the age 31-40 years in connective tissue dysplasia. At the age of 41-50, 51-60 years, at the boundary of connective tissue structures and periosteum, a pronounced sclerosis and deformation of delineation elements were observed; at the age of 31-40 years, the indicated changes were less pronounced. At the age of 31-40 years, the level of bone plate dissection has a local character, after 40 years, it has a generalized character.
CONCLUSION
Progressive osteoporosis of the mandible and incomplete amelogenesis are an obstacle to the correct and harmonious teething of the lower wisdom teeth after the age of 30.
PubMed: 35814839
DOI: 10.1016/j.sdentj.2022.05.002 -
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 -
BMC Oral Health Nov 2023Amelogenesis imperfecta (AI) is a developmental enamel defect affecting the structure of enamel, esthetic appearance, and the tooth masticatory function. Gene mutations...
BACKGROUND
Amelogenesis imperfecta (AI) is a developmental enamel defect affecting the structure of enamel, esthetic appearance, and the tooth masticatory function. Gene mutations are reported to be relevant to AI. However, the mechanism underlying AI caused by different mutations is still unclear. This study aimed to reveal the molecular pathogenesis in AI families with 2 novel pre-mRNA splicing mutations.
METHODS
Two Chinese families with AI were recruited. Whole-exome sequencing and Sanger sequencing were performed to identify mutations in candidate genes. Minigene splicing assays were performed to analyze the mutation effects on mRNA splicing alteration. Furthermore, three-dimensional structures of mutant proteins were predicted by AlphaFold2 to evaluate the detrimental effect.
RESULTS
The affected enamel in family 1 was thin, rough, and stained, which was diagnosed as hypoplastic-hypomature AI. Genomic analysis revealed a novel splicing mutation (NM_001142.2: c.570 + 1G > A) in the intron 6 of amelogenin (AMELX) gene in family 1, resulting in a partial intron 6 retention effect. The proband in family 2 exhibited a typical hypoplastic AI, and the splicing mutation (NM_031889.2: c.123 + 4 A > G) in the intron 4 of enamelin (ENAM) gene was observed in the proband and her father. This mutation led to exon 4 skipping. The predicted structures showed that there were obvious differences in the mutation proteins compared with wild type, leading to impaired function of mutant proteins.
CONCLUSIONS
In this study, we identified two new splicing mutations in AMELX and ENAM genes, which cause hypoplastic-hypomature and hypoplastic AI, respectively. These results expand the spectrum of genes causing AI and broaden our understanding of molecular genetic pathology of enamel formation.
Topics: Humans; Female; Amelogenin; Amelogenesis Imperfecta; Dental Enamel Proteins; Mutation; Mutant Proteins; Extracellular Matrix Proteins
PubMed: 37985977
DOI: 10.1186/s12903-023-03508-8 -
International Journal of Molecular... Jun 2020With increasing life expectancy, demands for dental tissue and whole-tooth regeneration are becoming more significant. Despite great progress in medicine, including... (Review)
Review
With increasing life expectancy, demands for dental tissue and whole-tooth regeneration are becoming more significant. Despite great progress in medicine, including regenerative therapies, the complex structure of dental tissues introduces several challenges to the field of regenerative dentistry. Interdisciplinary efforts from cellular biologists, material scientists, and clinical odontologists are being made to establish strategies and find the solutions for dental tissue regeneration and/or whole-tooth regeneration. In recent years, many significant discoveries were done regarding signaling pathways and factors shaping calcified tissue genesis, including those of tooth. Novel biocompatible scaffolds and polymer-based drug release systems are under development and may soon result in clinically applicable biomaterials with the potential to modulate signaling cascades involved in dental tissue genesis and regeneration. Approaches for whole-tooth regeneration utilizing adult stem cells, induced pluripotent stem cells, or tooth germ cells transplantation are emerging as promising alternatives to overcome existing in vitro tissue generation hurdles. In this interdisciplinary review, most recent advances in cellular signaling guiding dental tissue genesis, novel functionalized scaffolds and drug release material, various odontogenic cell sources, and methods for tooth regeneration are discussed thus providing a multi-faceted, up-to-date, and illustrative overview on the tooth regeneration matter, alongside hints for future directions in the challenging field of regenerative dentistry.
Topics: Animals; Biocompatible Materials; Dental Enamel; Drug Carriers; Humans; Odontogenesis; Regeneration; Signal Transduction; Stem Cells; Tissue Engineering; Tissue Scaffolds; Tooth
PubMed: 32512908
DOI: 10.3390/ijms21114031 -
Cureus Dec 2023Odontogenic anomalies encompass deviations in dental morphology, orientation, or spatial positioning within the mandibular structures. This study probed the frequency of...
BACKGROUND
Odontogenic anomalies encompass deviations in dental morphology, orientation, or spatial positioning within the mandibular structures. This study probed the frequency of such dental malformations among orthodontic patients receiving treatment in Riyadh City, Saudi Arabia. Furthermore, the study sought to discern variations in the manifestation of these dental anomalies related to gender and nationality.
MATERIALS AND METHODS
A retrospective analysis was conducted on 384 panoramic radiographs belonging to orthodontic patients (comprising 222 males and 162 females) who sought treatment at orthodontic clinics of a privately owned university hospital in Riyadh City between 2017 and 2019. The patient records were scrutinized for various dental abnormalities, including but not limited to dilacerated teeth, supernumerary teeth, congenital absence of teeth, impactions, hyperdontia, hypodontia, taurodontism, tooth rotation, and amelogenesis imperfecta. The Chi-square test was employed to assess the correlation between the prevalence of dental anomalies and variables such as gender and nationality. A p-value of less than 0.05 was deemed statistically significant for all tests.
RESULTS
Among the assessed sample size of orthodontic patients, dental impactions emerged as the most prevalent dental anomaly, affecting 246 patients (64.1%). This was followed by the occurrence of supernumerary teeth in 31 patients (8.1%), hyperdontia in 29 patients (7.6%), and congenital absence of teeth in 28 patients (7.3%). Other less frequently observed dental irregularities included dilacerated teeth in 23 patients (6%), amelogenesis imperfecta in 12 patients (3.1%), taurodontism in 12 patients (3.1%), and tooth rotations in five patients (1.3%). A statistically significant gender-based disparity was observed, with dental impactions being more prevalent among males (n=154; 69.4%) than females (n=92; 56.8%). Conversely, supernumerary teeth were more prevalent among females (n=24; 14.8%) than males (n=7; 3.2%). No significant variation in the prevalence of dental anomalies was discernible across different nationalities.
CONCLUSION
Impactions and the presence of supernumerary teeth were the predominant dental anomalies detected among the studied orthodontic patient population. The prevalence of dental anomalies exhibited discernible variations based on gender but not nationality. These disparities could potentially influence orthodontic outcomes, underscoring the necessity for meticulous examination and tailored orthodontic treatment planning.
PubMed: 38174162
DOI: 10.7759/cureus.49893 -
Journal of Clinical Medicine Jun 2023Individuals with amelogenesis imperfecta (AI) often present with malocclusions, especially a dental or skeletal anterior open bite (AOB). (Review)
Review
BACKGROUND
Individuals with amelogenesis imperfecta (AI) often present with malocclusions, especially a dental or skeletal anterior open bite (AOB).
OBJECTIVES
To evaluate the craniofacial characteristics in individuals with AI.
MATERIAL AND METHODS
A systematic literature search was conducted with the PubMed, Web of Science, Embase and Google Scholar databases to identify studies relating to the cephalometric characteristics of individuals with AI, without any language or publication date restrictions. The grey literature was searched using Google Scholar, Opengrey and Worldcat. Only studies with a suitable control group for comparison were included. Data extraction and a risk of bias assessment were carried out. A meta-analysis was performed using the random effects model for cephalometric variables that were evaluated in at least three studies.
RESULTS
The initial literature search yielded 1857 articles. Following the removal of duplicates and a screening of the records, seven articles were included in the qualitative synthesis, representing a total of 242 individuals with AI. Four studies were included in the quantitative synthesis. The meta-analysis results showed that individuals with AI present a smaller SNB angle and larger ANB angle than those of control groups in the sagittal plane. In the vertical plane, those with AI present a smaller overbite and larger intermaxillary angle than those without AI. No statistically significant differences were found for the SNA angle when comparing the two groups.
CONCLUSIONS
Individuals with AI seem to present with more vertical craniofacial growth, leading to an increased intermaxillary angle and decreased overbite. This possibly leads to a more retrognathic mandible with a larger ANB angle due to an anticipated posterior mandibular rotation.
PubMed: 37298021
DOI: 10.3390/jcm12113826 -
International Journal of Molecular... Jun 2024mutations cause X-linked amelogenesis imperfecta (AI), known as AI types IE, IIB, and IIC in Witkop's classification, characterized by hypoplastic (reduced thickness)...
mutations cause X-linked amelogenesis imperfecta (AI), known as AI types IE, IIB, and IIC in Witkop's classification, characterized by hypoplastic (reduced thickness) and/or hypomaturation (reduced hardness) enamel defects. In this study, we conducted whole exome analyses to unravel the disease-causing mutations for six AI families. Splicing assays, immunoblotting, and quantitative RT-PCR were conducted to investigate the molecular and cellular effects of the mutations. Four pathogenic variants (NM_182680.1:c.2T>C; c.29T>C; c.77del; c.145-1G>A) and a whole gene deletion (NG_012494.2:g.307534_403773del) were identified. The affected individuals exhibited enamel malformations, ranging from thin, poorly mineralized enamel with a "snow-capped" appearance to severe hypoplastic defects with minimal enamel. The c.145-1G>A mutation caused a -1 frameshift (NP_001133.1:p.Val35Cysfs*5). Overexpression of c.2T>C and c.29T>C demonstrated that mutant amelogenin proteins failed to be secreted, causing elevated endoplasmic reticulum stress and potential cell apoptosis. This study reveals a genotype-phenotype relationship for -associated AI: While amorphic mutations, including large deletions and 5' truncations, of cause hypoplastic-hypomaturation enamel with snow-capped teeth (AI types IIB and IIC) due to a complete loss of gene function, neomorphic variants, including signal peptide defects and 3' truncations, lead to severe hypoplastic/aplastic enamel (AI type IE) probably caused by "toxic" cellular effects of the mutant proteins.
Topics: Amelogenesis Imperfecta; Humans; Amelogenin; Male; Female; Genetic Association Studies; Mutation; Pedigree; Phenotype; Child; Endoplasmic Reticulum Stress; Genotype; Exome Sequencing
PubMed: 38892321
DOI: 10.3390/ijms25116132