Search Results (38)

Excessive fluoride ingestion during tooth development can cause dental fluorosis. Previously, we reported that fluoride activates histone acetyltransferase (HAT) to acetylate p53, promoting fluoride toxicity in mouse ameloblast-like LS8 cells. However, the roles of HAT and histone acetylation status in fluoride-mediated gene expression remain unidentified. Here, we demonstrate that fluoride-mediated histone modification causes gene expression alterations in LS8 cells. LS8 cells were treated with or without fluoride followed by ChIP-Seq analysis of H3K27ac. Genes were identified by differential H3K27ac peaks within ±1 kb from transcription start sites. The levels of mRNA of identified genes were assessed using rea-time PCR (qPCR). Fluoride increased H3K27ac peaks associated with Bax, p21, and Mdm2 genes and upregulated their mRNA levels. Fluoride decreased H3K27ac peaks and p53, Bad, and Bcl2 had suppressed transcription. HAT inhibitors (Anacardic acid or MG149) suppressed fluoride-induced mRNA of p21 and Mdm2, while fluoride and the histone deacetylase (HDAC) inhibitor sodium butyrate increased Bad and Bcl2 expression above that of fluoride treatment alone. To our knowledge, this is the first study that demonstrates epigenetic regulation via fluoride treatment via H3 acetylation. Further investigation is required to elucidate epigenetic mechanisms of fluoride toxicity in enamel development. Full article

Amelogenesis imperfecta (AI) is a genetic disease characterized by poor formation of tooth enamel. AI occurs due to mutations, especially in AMEL, ENAM, KLK4, MMP20, and FAM83H, associated with changes in matrix proteins, matrix proteases, cell-matrix adhesion proteins, and transport proteins of enamel. Due to the wide variety of phenotypes, the diagnosis of AI is complex, requiring a genetic test to characterize it better. Thus, there is a demand for developing low-cost, noninvasive, and accurate platforms for AI diagnostics. This case-control pilot study aimed to test salivary vibrational modes obtained in attenuated total reflection fourier-transformed infrared (ATR-FTIR) together with machine learning algorithms: linear discriminant analysis (LDA), random forest, and support vector machine (SVM) could be used to discriminate AI from control subjects due to changes in salivary components. The best-performing SVM algorithm discriminates AI better than matched-control subjects with a sensitivity of 100%, specificity of 79%, and accuracy of 88%. The five main vibrational modes with higher feature importance in the Shapley Additive Explanations (SHAP) were 1010 cm⁻¹, 1013 cm⁻¹, 1002 cm⁻¹, 1004 cm⁻¹, and 1011 cm⁻¹ in these best-performing SVM algorithms, suggesting these vibrational modes as a pre-validated salivary infrared spectral area as a potential biomarker for AI screening. In summary, ATR-FTIR spectroscopy and machine learning algorithms can be used on saliva samples to discriminate AI and are further explored as a screening tool. Full article

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, Ilex guayusa and Piper marginatum, 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 I. guayusa and P. marginatum 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, I. guayusa and P. marginatum 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. Full article

AMELX 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 AMELX 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 AMELX 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 AMELX-associated AI: While amorphic mutations, including large deletions and 5′ truncations, of AMELX 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. Full article

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. Full article

Hereditary conditions that affect tooth enamel in quantity and/or quality are called amelogenesis imperfecta (AI). AI can occur as an isolated condition or as a symptom of a syndrome. An OMIM search with the term “AI” yielded 79 result entries. Mutations in the same gene cause syndromic or non-syndromic AI, depending on the nature of the mutations. In this study, we recruited two AI families and performed mutational analysis using whole-exome sequencing. The proband of family 1, with hypoplastic pitted AI and mild localized atopic dermatitis, had compound heterozygous COL17A1 mutations (paternal NM_000494.4: c.3598G>T, p.Asp1200Tyr and maternal c.1700G>A, p.Gly567Glu). The proband of family 2, with hypoplastic pitted AI and Jervell and Lange-Nielsen syndrome, had a recurrent LAMB3 mutation (NM_000228.3: c.3463_3475del, p.(Glu1155Thrfs*51)) in addition to compound heterozygous mutations in the KCNQ1 gene. Full article

Fluoride (F) ions actively participate in the dental enamel remineralisation process and inhibit the activity of cariogenic bacteria of the oral biofilm. However, increased systemic intake of F during critical periods of amelogenesis can lead to dental fluorosis (DF). The necessity of our study stemmed from the growing consumption of bottled water, as water is one of the primary sources of F in humans, and labelling F concentration is optional. Our aim was to evaluate the F concentration in bottled natural mineral or spring still waters available on the market in Iasi, Romania. We purchased forty different brands of still bottled water from the major grocery stores and tested them using an ion-selective electrode method. The reliability of the data was assessed by the intraclass correlation coefficient (ICC), while the differences between the obtained and labelled F values were examined using a paired samples t-test. The tested F levels ranged between 0.0338 and 4.6262 milligrams per litter (mg/L). The majority of the samples, around 85% recorded F values ranging from 0.232 to 0.0338 mg/L, offering slight or no benefit in caries prevention. Another 10% of the samples had F values ranging between 0.3 and 0.4 mg/L and could provide a dental health benefit. A percentage of 5% of the tested samples recorded F levels above the optimal level of 0.7 mg/L, as set by the American Dental Association (ADA) and the United States Department of Health and Human Services (U.S. HHS). This elevated F concentration poses a potential risk for DF in infants and toddlers, indicating that regular consumption of these samples may be unsafe. Full article

Molar incisor hypomineralization (MIH) is a significant health problem that can affect the child’s quality of life by negatively affecting their esthetics and function. This review aimed to summarize the etiology and pathogenesis of MIH. It also aimed to summarize the recent studies on MIH in children and adolescents, focusing on diagnosis, prevention, and clinical management. An electronic search on the PubMed, Cochrane Database of Systematic Reviews, MEDLINE, MedlinePlus, WHO reports, and Google Scholar databases was performed. The volume of research on the etiology, presentation, and clinical management of MIH is still expanding. The creation and validation of indices for the diagnosis and management of MIH, as well as any potential genetic aspects appear to be the main areas of current research. Notably, MIH was linked to childhood illnesses, the use of antibiotics, and early childhood fever. Although many studies discuss the different options for managing MIH lesions, evidence-based studies that address the long-term outcomes of MIH are still lacking. Indeed, future clinical studies should be directed to evaluate the impact of each systemic etiological factor and its different types of management on normal amelogenesis. Regarding the diagnosis, future research should focus on the pre-eruption diagnosis and early approaches to prevent the post-eruption breakdown and caries. Regarding the treatment of MIH, future investigations should emphasize further improvements in adhesion and the use of new materials and techniques, such as digital dentistry. Full article

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. Full article

Pediatric esthetic dentistry is a sensitive technique, as children can be less cooperative; hence, minimal appointments are preferred. The most conservative treatment modality for anterior esthetic rehabilitation is using direct composite veneer restorations. In many instances, esthetic improvements using composite resin are the only possible option until the growth phase of the pediatric patient is complete. In this article, we present three different case scenarios in young teenagers with different treatment needs requiring esthetic restorations. The first case report is a patient with amelogenesis imperfecta, the second is with generalized spacing, and the third is with localized microdontia. All three patients were followed up for six months post direct composite veneering and were highly satisfied with their treatment outcomes, which boosted their self-confidence. Full article

Dental enamel is a specialized tissue that has adapted over millions of years of evolution to enhance the survival of a variety of species. In humans, enamel evolved to form the exterior protective layer for the crown of the exposed tooth crown. Its unique composition, structure, physical properties and attachment to the underlying dentin tissue allow it to be a resilient, although not self-repairing, tissue. The process of enamel formation, known as amelogenesis, involves epithelial-derived cells called ameloblasts that secrete a unique extracellular matrix that influences the structure of the mineralizing enamel crystallites. There are over 115 known genetic conditions affecting amelogenesis that are associated with enamel phenotypes characterized by either a reduction of enamel amount and or mineralization. Amelogenesis involves many processes that are sensitive to perturbation and can be altered by numerous environmental stressors. Genetics, epigenetics, and environment factors can influence enamel formation and play a role in resistance/risk for developmental defects and the complex disease, dental caries. Understanding why and how enamel is affected and the enamel phenotypes seen clinically support diagnostics, prognosis prediction, and the selection of treatment approaches that are appropriate for the specific tissue defects (e.g., deficient amount, decreased mineral, reduced insulation and hypersensitivity). The current level of knowledge regarding the heritable enamel defects is sufficient to develop a new classification system and consensus nosology that effectively communicate the mode of inheritance, molecular defect/pathway, and the functional aberration and resulting enamel phenotype. Full article

Amelogenesis imperfecta (AI) is a heterogeneous collection of hereditary enamel defects. The affected enamel can be classified as hypoplastic, hypomaturation, or hypocalcified in form. A better understanding of normal amelogenesis and improvements in our ability to diagnose AI through genetic testing can be realized through more complete knowledge of the genes and disease-causing variants that cause AI. In this study, mutational analysis was performed with whole exome sequencing (WES) to identify genetic etiology underlying the hypomaturation AI condition in affected families. Mutational analyses identified biallelic WDR72 mutations in four hypomaturation AI families. Novel mutations include a homozygous deletion and insertion mutation (NM_182758.4: c.2680_2699delinsACTATAGTT, p.(Ser894Thrfs*15)), compound heterozygous mutations (paternal c.2332dupA, p.(Met778Asnfs*4)) and (maternal c.1287_1289del, p.(Ile430del)) and a homozygous 3694 bp deletion that includes exon 14 (NG_017034.2:g.96472_100165del). A homozygous recurrent mutation variant (c.1467_1468delAT, p.(Val491Aspfs*8)) was also identified. Current ideas on WDR72 structure and function are discussed. These cases expand the mutational spectrum of WDR72 mutations causing hypomaturation AI and improve the possibility of genetic testing to accurately diagnose AI caused by WDR72 defects. Full article

Background: A prompt and accurate diagnosis of developmental defects of enamel (DDE) is mandatory for proper treatment management. This cross-sectional survey, designed and carried out using anonymous self-administered questionnaires, aimed to assess dental and dental hygiene students’ knowledge and their capability to identify different enamel development defects. Methods: The questionnaire consisted of twenty-eight closed-ended questions. Two different samples of undergraduate students were selected and enrolled: a group of dental hygiene (GDH) students and a group of dental (GD) students. A multivariate logistic regression was performed by adopting the correct answers as explanatory variables to assess the difference between the two groups. Results: Overall, 301 completed questionnaires were analyzed: 157 from the GDH and 144 from the GD. The dental student group showed better knowledge than the GDH of enamel hypomineralization and hypoplasia (p = 0.03 for both). A quarter (25.25%) of the total sample correctly identified the period of development of dental fluorosis with a statistically significant difference between the groups (p < 0.01). Amelogenesis imperfecta (AI) was identified as a genetic disease by 64.45% of the sample, with a better performance from the GD (p = 0.01), while no statistical differences were found between the groups regarding molar incisor hypomineralization. Multivariate analysis showed that AI (OR = 0.40, [0.23;0.69], p < 0.01) and caries lesion (OR = 0.58, [0.34;0.94], p = 0.03) were better recognized by the GD. Conclusions: Disparities exist in the knowledge and management of DDE among dental and dental hygiene students in Italy; however, significant knowledge gaps were found in both groups. Education on the diagnosis and treatment of DDE during the training for dental and dental hygiene students needs to be strongly implemented. Full article

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders of dental enamel. X-linked AI results from disease-causing variants in the AMELX gene. In this paper, we characterise the genetic aetiology and enamel histology of female AI patients from two unrelated families with similar clinical and radiographic findings. All three probands were carefully selected from 40 patients with AI. In probands from both families, scanning electron microscopy confirmed hypoplastic and hypomineralised enamel. A neonatal line separated prenatally and postnatally formed enamel of distinctly different mineralisation qualities. In both families, whole exome analysis revealed the intron variant NM_182680.1: c.103-3T>C, located three nucleotides before exon 4 of the AMELX gene. In family I, an additional variant, c.2363G>A, was found in exon 5 of the FAM83H gene. This report illustrates a variant in the AMELX gene that was not previously reported to be causative for AI as well as an additional variant in the FAM83H gene with probably limited clinical significance. Full article

There is currently no consensus among researchers on the optimal level of fluoride for human growth and health. As drinking water is not the sole source of fluoride for humans, and fluoride can be found in many food sources, this work aimed to determine the incidence and severity of dental fluorosis in Poland, in areas where a low fluoride content characterizes the drinking water, and to assess the impact of fluoride on the enamel composition and microstructure. The dental examination involved 696 patients (aged 15–25 years) who had since birth lived in areas where the fluoride concentration in drinking water did not exceed 0.25 mg/L. The severity of the condition was evaluated using the Dean’s Index. Both healthy teeth and teeth with varying degrees of fluorosis underwent laboratory tests designed to assess the total protein and fluoride content of the enamel. Protein amount was assessed spectrophotometrically while the level of fluoride ions was measured by DX-120 ion chromatography. The clinical study revealed 89 cases (12.8%) of dental fluorosis of varying severity. The enamel of teeth with mild and moderate fluorosis contained a significantly higher protein (p-value < 0.001 and 0.002, respectively) and fluoride level (p < 0.001) than those with no clinical signs of fluorosis. SEM images showed irregularities in the structure of the fluorotic enamel. An excessive fluoride level during amelogenesis leads to adverse changes in the chemical composition of tooth enamel and its structure. Moreover, dental fluorosis present in areas where drinking water is low in fluorides indicates a need to monitor the supply of fluoride from other possible sources, regardless of its content in the water. Full article