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Dentistry Journal Jun 2024Amelogenesis imperfecta is a hereditary disorder affecting dental enamel. Among its phenotypes, hypocalcified AI is characterized by mineral deficiency, leading to...
BACKGROUND
Amelogenesis imperfecta is a hereditary disorder affecting dental enamel. Among its phenotypes, hypocalcified AI is characterized by mineral deficiency, leading to tissue wear and, consequently, dental sensitivity. Excessive fluoride intake (through drinking water, fluoride supplements, toothpaste, or by ingesting products such as pesticides or insecticides) can lead to a condition known as dental fluorosis, which manifests as stains and teeth discoloration affecting their structure. Our recent studies have shown that extracts from Colombian native plants, and , deposit mineral ions such as phosphate and orthophosphate into the dental enamel structure; however, it is unknown whether these extracts produce toxic effects on the dental pulp.
OBJECTIVE
To assess cytotoxicity effects on human dental pulp stem cells (hDPSCs) exposed to extracts isolated from and . and, hence, their safety for clinical use.
METHODS
Raman spectroscopy, fluorescence microscopy, and flow cytometry techniques were employed. For Raman spectroscopy, hDPSCs were seeded onto nanobiochips designed to provide surface-enhanced Raman spectroscopy (SERS effect), which enhances their Raman signal by several orders of magnitude. After eight days in culture, and extracts at different concentrations (10, 50, and 100 ppm) were added. Raman measurements were performed at 0, 12, and 24 h following extract application. Fluorescence microscopy was conducted using an OLIMPUS fv1000 microscope, a live-dead assay was performed using a kit employing a BD FACS Canto TM II flow cytometer, and data analysis was determined using a FlowJo program.
RESULTS
The Raman spectroscopy results showed spectra consistent with viable cells. These findings were corroborated using fluorescence microscopy and flow cytometry techniques, confirming high cellular viability.
CONCLUSIONS
The analyzed extracts exhibited low cytotoxicity, suggesting that they could be safely applied on enamel for remineralization purposes. The use of nanobiochips for SERS effect improved the cell viability assessment.
PubMed: 38920890
DOI: 10.3390/dj12060189 -
Journal of Dentistry Jun 2024To summarize studies published between 2017 and 2023 examining the clinical diagnosis and restorative management of amelogenesis imperfecta (AI) in children and... (Review)
Review
OBJECTIVE
To summarize studies published between 2017 and 2023 examining the clinical diagnosis and restorative management of amelogenesis imperfecta (AI) in children and adolescents.
DATA
The review incorporated publications on clinical diagnosis, patient-reported outcomes, clinical trials, cohort studies, and case reports that included individuals below 19 years of age with non-syndromic AI.
SOURCES
A literature search was conducted across electronic databases, PubMed, Web of Science, and CINAHL, including papers published between 2017 and 2023. The search yielded 335 unique results, of which 38 were eligible for inclusion.
RESULTS
New evidence on the genetic background of AI makes it now advisable to recommend genetic testing to supplement a clinical AI diagnosis. The discussions of the dental profession and the public on social media do not always incorporate recent scientific evidence. Interview studies are finding that the impact of AI on quality of life is more severe than previously appreciated. New evidence suggests that single-tooth ceramic crowns should be the first choice of treatment. Due to incomplete reporting, case reports have been of limited value.
CONCLUSION
In young patients with AI symptoms of pain and hypersensitivity decreased, and aesthetics were improved following all types of restorative therapy. Resin composite restorations were mainly performed in cases with hypoplastic AI and mild symptoms. Single tooth ceramic crown restorations have a high success rate in all types of AI and can be used in young individuals with AI.
CLINICAL SIGNIFICANCE
Prosthetic rehabilitation in adolescents with severe AI is cost effective, improves esthetics, reduces tooth sensitivity, and improves oral health-related quality of life.
PubMed: 38909645
DOI: 10.1016/j.jdent.2024.105149 -
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 -
Head & Face Medicine Jun 2024Amelogenesis imperfecta (AI) is a genetically determined, non-syndromic enamel dysplasia that may manifest as hypoplasia, hypomaturation, or hypocalcification and can...
INTRODUCTION
Amelogenesis imperfecta (AI) is a genetically determined, non-syndromic enamel dysplasia that may manifest as hypoplasia, hypomaturation, or hypocalcification and can commonly be classified into four primary groups. In this retrospective analysis, specific orofacial characteristics are described and associated with each of the AI types based on a patient cohort from Witten/Herdecke University, Germany.
METHODS
Data from 19 patients (ten male and nine female, mean age 12.27 ± 4.06 years) with AI who presented at the Department of Orthodontics between July 2011 and December 2023 were analyzed. Baseline skeletal and dental conditions were assessed, including the presence of hypodontia, displacements, and taurodontism. AI was classified into classes I-IV based on phenotype. Treatment needs were evaluated according to the main findings following the German KIG classification, while the radiological enamel situation was determined using panoramic radiographs.
RESULTS
An approximately equal distribution between classes II and III was found and a slight inclination toward a dolichofacial configuration (ΔML-NSL: 5.07 ± 9.23°, ΔML-NL: 4.24 ± 8.04°). Regarding orthodontic findings, disturbance in tooth eruption as well as open bite were the most prevalent issues (both 36.8%, n = 7). The most common AI classes were type I and II, which show an almost even distribution about the skeletal classes in sagittal dimension, while dolichofacial configuration was found most frequently in vertical dimension.
CONCLUSION
Both clinical and radiological orthodontic findings in context with AI are subject to extensive distribution. It seems that no specific orofacial findings can be confirmed in association with AI with regard to the common simple classes I-IV. It may be more appropriate to differentiate the many subtypes according to their genetic aspects to identify possible associated orthodontic findings.
Topics: Humans; Amelogenesis Imperfecta; Male; Female; Retrospective Studies; Child; Adolescent; Germany; Radiography, Panoramic; Orthodontics, Corrective; Malocclusion
PubMed: 38877506
DOI: 10.1186/s13005-024-00436-y -
Archives of Oral Biology Sep 2024This study aimed to reveal the effects of SET domain bifurcated 1 (SETDB1) on epithelial cells during tooth development.
OBJECTIVE
This study aimed to reveal the effects of SET domain bifurcated 1 (SETDB1) on epithelial cells during tooth development.
DESIGN
We generated conditional knockout mice (Setdb1 mice), in which Setdb1 was deleted only in epithelial cells. At embryonic day 14.5 (E14.5), immunofluorescence staining was performed to confirm the absence of SETDB1 within the epithelium of tooth embryos from Setdb1 mice. Mouse embryos were harvested after reaching embryonic day 13.5 (E13.5), and sections were prepared for histological analysis. To observe tooth morphology in detail, electron microscopy and micro-CT analysis were performed at postnatal months 1 (P1M) and 6 (P6M). Tooth embryos were harvested from postnatal day 7 (P7) mice, and the epithelial components of the tooth embryos were isolated and examined using quantitative RT-PCR for the expression of genes involved in tooth development.
RESULTS
Setdb1 mice exhibited enamel hypoplasia, brittle and fragile dentition, and significant abrasion. Coronal sections displayed abnormal ameloblast development, including immature polarization, and a thin enamel layer that detached from the dentinoenamel junction at P7. Electron microscopic analysis revealed characteristic findings such as an uneven surface and the absence of an enamel prism. The expression of Msx2, Amelogenin (Amelx), Ameloblastin (Ambn), and Enamelin (Enam) was significantly downregulated in the epithelial components of tooth germs in Setdb1 mice.
CONCLUSIONS
These results indicate that SETDB1 in epithelial cells is important for tooth development and clarify the relationship between the epigenetic regulation of SETDB1 and amelogenesis imperfecta for the first time.
Topics: Animals; Mice; Histone-Lysine N-Methyltransferase; Epithelial Cells; Mice, Knockout; Odontogenesis; Amelogenin; X-Ray Microtomography; Ameloblasts; Dental Enamel; Tooth; Microscopy, Electron; Real-Time Polymerase Chain Reaction
PubMed: 38875772
DOI: 10.1016/j.archoralbio.2024.106026 -
STAR Protocols Jun 2024Adult humans cannot regenerate the enamel-forming cell type, ameloblasts. Hence, human induced pluripotent stem cell (hiPSC)-derived ameloblasts are valuable for...
Adult humans cannot regenerate the enamel-forming cell type, ameloblasts. Hence, human induced pluripotent stem cell (hiPSC)-derived ameloblasts are valuable for investigating tooth development and regeneration. Here, we present a protocol for generating three-dimensional induced early ameloblasts (ieAMs) utilizing serum-free media and growth factors. We describe steps for directing hiPSCs toward oral epithelium and then toward ameloblast fate. These cells can form suspended early ameloblast organoids. This approach is critical for understanding, treating, and promoting regeneration in diseases like amelogenesis imperfecta. For complete details on the use and execution of this protocol, please refer to Alghadeer et al..
Topics: Ameloblasts; Humans; Culture Media, Serum-Free; Induced Pluripotent Stem Cells; Cell Culture Techniques; Intercellular Signaling Peptides and Proteins; Cell Differentiation; Cells, Cultured
PubMed: 38824640
DOI: 10.1016/j.xpro.2024.103100 -
Matrix Biology : Journal of the... Aug 2024Extracellular matrix proteins play crucial roles in the formation of mineralized tissues like bone and teeth via multifunctional mechanisms. In tooth enamel,... (Review)
Review
Extracellular matrix proteins play crucial roles in the formation of mineralized tissues like bone and teeth via multifunctional mechanisms. In tooth enamel, ameloblastin (Ambn) is one such multifunctional extracellular matrix protein implicated in cell signaling and polarity, cell adhesion to the developing enamel matrix, and stabilization of prismatic enamel morphology. To provide a perspective for Ambn structure and function, we begin this review by describing dental enamel and enamel formation (amelogenesis) followed by a description of enamel extracellular matrix. We then summarize the established domains and motifs in Ambn protein, human amelogenesis imperfecta cases, and genetically engineered mouse models involving mutated or null Ambn. We subsequently delineate in silico, in vitro, and in vivo evidence for the amphipathic helix in Ambn as a proposed cell-matrix adhesive and then more recent in vitro evidence for the multitargeting domain as the basis for dynamic interactions of Ambn with itself, amelogenin, and membranes. The multitargeting domain facilitates tuning between Ambn-membrane interactions and self/co-assembly and supports a likely overall role for Ambn as a matricellular protein. We anticipate that this review will enhance the understanding of multifunctional matrix proteins by consolidating diverse mechanisms through which Ambn contributes to enamel extracellular matrix mineralization.
Topics: Humans; Animals; Dental Enamel Proteins; Amelogenesis; Amelogenesis Imperfecta; Mice; Dental Enamel; Extracellular Matrix; Amelogenin; Cell Adhesion
PubMed: 38815936
DOI: 10.1016/j.matbio.2024.05.007 -
Dentistry Journal May 2024Familial isolated hypoparathyroidism is a rare genetic disorder due to no or low production of the parathyroid hormone, disturbing calcium and phosphate regulation. The...
OBJECTIVE
Familial isolated hypoparathyroidism is a rare genetic disorder due to no or low production of the parathyroid hormone, disturbing calcium and phosphate regulation. The resulting hypocalcemia may lead to dental abnormalities, such as enamel hypoplasia. The aim of this paper was to describe the full-mouth rehabilitation of a 15-year-old girl with chronic hypocalcemia due to a rare congenital hypoparathyroidism.
CLINICAL CONSIDERATIONS
In this patient, in the young adult dentition, conservative care was preferred. Onlays or stainless-steel crowns were performed on the posterior teeth, and direct or indirect (overlays and veneerlays) were performed on the maxillary premolars, canines, and incisors, using a digital wax-up. The mandibular incisors were bleached. The treatment clearly improved the patient's oral quality of life, with fewer sensitivities, better chewing, and aesthetic satisfaction. The difficulties were the regular monitoring and the limited compliance of the patient.
CONCLUSION
Despite no clinical feedback in the literature, generalized hypomineralized/hypoplastic teeth due to hypoparathyroidism in a young patient can be treated as amelogenesis imperfecta (generalized enamel defects) with a conservative approach for medium-term satisfactory results.
HIGHLIGHTS
This study provides new insights into the management of enamel hypoplasia caused by familial isolated hypoparathyroidism, helping to improve patient outcomes in similar cases.
PubMed: 38786528
DOI: 10.3390/dj12050130 -
Archives of Oral Biology Aug 2024To identify the genetic cause of a Chinese family with hypomaturation amelogenesis imperfecta (AI) and to characterize the structure of GPR68 mutated enamel in order to...
OBJECTIVES
To identify the genetic cause of a Chinese family with hypomaturation amelogenesis imperfecta (AI) and to characterize the structure of GPR68 mutated enamel in order to develop a deeper understanding of the role of the GPR68 protein during the intricate process of amelogenesis.
DESIGN
One Chinese family with generalized hypomaturation AI was recruited. Two of the third molars from the proband were subjected to scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). Whole exome sequencing (WES) was performed, and the identified mutation was confirmed by Sanger sequencing. Bioinformatics studies were further conducted to analyze the potential deleterious effects of the mutation.
RESULTS
The proband presented with a hypomaturation AI phenotype, characterized by fragile and discolored enamel surface. The AI enamel showed prismatic structure, which was sporadically obscured by areas of amorphous material and porous structure. EDX analysis showed the proband's enamel demonstrated a significant decrease in calcium and phosphorus content and a significant increase in oxygen compared with normal enamel. A novel homozygous mutation of G protein-coupled receptor 68 (GPR68) (c .149 T > A, p.Ile50Asn) was identified in the proband. Bioinformatics analysis indicated that the mutation site displayed a high level of evolutionary conservation among species, and the mutation might impact the stability and conformation of the protein.
CONCLUSION
The novel homozygous GPR68 mutation resulted in hypomaturation AI. We first described the effect of GPR68 mutation on enamel structure. Our results provide new genetic evidence that mutations involved in GPR68 contribute to hypomaturation AI.
Topics: Female; Humans; Male; Amelogenesis Imperfecta; China; Computational Biology; Dental Enamel; Exome Sequencing; Microscopy, Electron, Scanning; Mutation; Pedigree; Phenotype; Receptors, G-Protein-Coupled; Spectrometry, X-Ray Emission
PubMed: 38761453
DOI: 10.1016/j.archoralbio.2024.105991 -
Swiss Dental Journal Feb 2024The aim of the treatment of this case was to restore the form, function and aesthetics of all teeth in a patient with amelogenesis imperfecta within the age limit of the...
The aim of the treatment of this case was to restore the form, function and aesthetics of all teeth in a patient with amelogenesis imperfecta within the age limit of the disability insurance (IV). Single-tooth zirconia crowns were selected as the treatment of choice and cemented with a conventional glass ionomer cement. For the maintenance of the oral rehabilitation and the protection of the reconstructions a michigan splint was produced and instructed to be carried over night.
Topics: Humans; Amelogenesis Imperfecta; Crowns; Glass Ionomer Cements; Zirconium; Female; Male; Esthetics, Dental; Dental Prosthesis Design; Occlusal Splints
PubMed: 38739045
DOI: 10.61872/sdj-2024-03-02