Solitary median maxillary central incisor (SMMCI) is a unique developmental anomaly in primary dentition. It involves central incisor tooth germs and may or may not be associated with other anomalies. Its presence, concomitant with fusion of right mandibular incisors has not previously been reported. A 5-year-old girl was presented with a single symmetrical primary maxillary incisor at the midline, with the absence of labial frenulum, an indistinct philtrum and a prominent midpalatal ridge. There was an associated fused tooth in the right incisor region and radiographic examination confirmed only one maxillary central incisor in both the dentitions. Family history revealed that the father of the girl also had a similar anomaly providing probable evidence of etiological role for heredity in SMMCI.

The purpose of this study involving a sample of children with single central incisor crossbite was to determine the relationship between clinical crown lengths of the crossbite and noncrossbite mandibular incisors, incisor irregularity, and orthodontic correction of the crossbite. In addition, for comparison, the normal maturational change in position of the labial gingival margin of mandibular incisors not undergoing orthodontic correction was examined. Twenty-one children treated for single central incisor crossbite were matched individually by gender and age to a comparison group. Pre- and post-treatment mandibular central incisor crown lengths and incisor irregularity were measured. In 10 of the 21 anterior crossbite cases, the crown length of the crossbite incisor was more than 1.5 mm greater than that of the noncrossbite incisor. This difference improved with orthodontic treatment by a combination of apical movement of the gingival margin of the noncrossbite incisor (0.9 +/- 0.8 mm) and coronal movement (0.2 +/- 0.6 mm) of the gingival margin of the crossbite incisor. In contrast, for the remaining 11 anterior crossbites without such a crown length difference, and for the comparison cases, the gingival margins of both mandibular central incisors moved equally from pre- to post-treatment by 0.5 +/- 0.5 mm in an apical direction. Pretreatment crown length difference between crossbite and noncrossbite incisor was associated strongly to incisor irregularity (P < or = 0.005, r = 0.65). Orthodontic correction of the crossbite produced an improvement in irregularity index (IR) that was greatest in those anterior crossbite cases with a pretreatment crown length difference.(ABSTRACT TRUNCATED AT 250 WORDS)

To test the hypothesis that in profile smiling view, for ideal aesthetics, a tangent to the labial face of the maxillary central incisor crowns should be approximately parallel to the true vertical line and thereby perpendicular to the true horizontal line.

Molar incisor hypomineralization (MIH) is an enamel condition characterized by lesions ranging in color from white to brown which present rapid caries progression, and mainly affects permanent first molars and incisors. These enamel defects usually occur when there are disturbances during the mineralization or maturation stage of amelogenesis. Both genetic and environmental factors have been suggested to play roles in MIH's development, but no conclusive risk factors have shown the source of the disease. During head and neck development, the interferon regulatory factor 6 (IRF6) gene is involved in the structure formation of the oral and maxillofacial regions, and the transforming growth factor alpha (TGFA) is an essential cell regulator, acting during proliferation, differentiation, migration and apoptosis. In this present study, it was hypothesized that these genes interact and contribute to predisposition of MIH. Environmental factors affecting children that were 3 years of age or older were also hypothesized to play a role in the disease etiology. Those factors included respiratory issues, malnutrition, food intolerance, infection of any sort and medication intake. A total of 1,065 salivary samples from four different cohorts were obtained, and DNA was extracted from each sample and genotyped for nine different single nucleotide polymorphisms. Association tests and logistic regression implemented in PLINK were used for analyses. A potential interaction between TGFA rs930655 with all markers tested in the cohort from Turkey was identified. These interactions were not identified in the remaining cohorts. Associations (p<0.05) between the use of medication after three years of age and MIH were also found, suggesting that conditions acquired at the age children start to socialize might contribute to the development of MIH.

Tooth formation can be affected by various factors, such as oral disease, drug administration, and systemic illness, as well as internal conditions including dentin formation. Dyslipidemia is an important lifestyle disease, though the relationship of aberrant lipid metabolism with tooth formation has not been clarified. This study was performed to examine the effects of dyslipidemia on tooth formation and tooth development. Dyslipidemia was induced in mice by giving a high-fat diet (HFD) for 12 weeks. Additionally, LDL receptor-deficient (Ldlr-/-) strain mice were used to analyze the effects of dyslipidemia and lipid metabolism in greater detail. In the HFD-fed mice, incisor elongation was decreased and pulp was significantly narrowed, while histological findings revealed disappearance of predentin. In Ldlr-/- mice fed regular chow, incisor elongation showed a decreasing trend and pulp a narrowing trend, while predentin changes were unclear. Serum lipid levels were increased in the HFD-fed wild-type (WT) mice, while Ldlr-/- mice given the HFD showed the greatest increase. These results show important effects of lipid metabolism, especially via the LDL receptor, on tooth homeostasis maintenance. In addition, they suggest a different mechanism for WT and Ldlr-/- mice, though the LDL receptor pathway may not be the only factor involved.

Uprighting incisors is particularly important with clear aligner therapy as incisor tip determines the mesio-distal space needed in the arch, and consequently the fit of the aligner. The objective of this study was to investigate the accuracy of ClinCheck® software to predict lower incisor tip by comparing digitally prescribed movements with actual clinical outcomes and to determine whether the presence of a vertically orientated rectangular composite attachment influences the efficacy of incisor tip.

The aim of the study is to compare the frequency and the distribution of molar incisor hypomineralization (MIH) in children with intellectual disabilities.

Objective: An insufficient mineralization (hypomineralization) in the teeth during the maturation stage of amelogenesis cause defects in 3-44% of children. Here, we describe for the first time the microbiota associated with these defects and compared it to healthy teeth within the same subjects. Methods: Supragingival dental plaque was sampled from healthy and affected teeth from 25 children with molar-incisor hypomineralization (MIH). Total DNA was extracted and the 16S rRNA gene was sequenced by Illumina sequencing in order to describe the bacterial composition. Results: We detected a higher bacterial diversity in MIH samples, suggesting better bacterial adhesion or higher number of niches in those surfaces. We found the genera Catonella, Fusobacterium, Campylobacter, Tannerella, Centipeda, Streptobacillus, Alloprevotella and Selenomonas associated with hypomineralized teeth, whereas Rothia and Lautropia were associated with healthy sites. Conclusion: The higher protein content of MIH-affected teeth could favour colonization by proteolytic microorganisms. The over-representation of bacteria associated with endodontic infections and periodontal pathologies suggests that, in addition to promote caries development, MIH could increase the risk of other oral diseases.

The aim of this study was to assess the effect of overjet and overbite on profile shape in middle-aged individuals.

In order to improve our understanding on the microbial complexity associated with Grade C/molar-incisor pattern periodontitis (GC/MIP), we surveyed the oral and fecal microbiomes of GC/MIP and compared to non-affected individuals (Control). Seven Afro-descendants with GC/MIP and seven age/race/gender-matched controls were evaluated. Biofilms from supra/subgingival sites (OB) and feces were collected and submitted to 16S rRNA sequencing. Aggregatibacter actinomycetemcomitans (Aa) JP2 clone genotyping and salivary nitrite levels were determined. Supragingival biofilm of GC/MIP presented greater abundance of opportunistic bacteria. Selenomonas was increased in subgingival healthy sites of GC/MIP compared to Control. Synergistetes and Spirochaetae were more abundant whereas Actinobacteria was reduced in OB of GC/MIP compared to controls. Aa abundance was 50 times higher in periodontal sites with PD≥ 4 mm of GC/MIP than in controls. GC/MIP oral microbiome was characterized by a reduction in commensals such as Kingella, Granulicatella, Haemophilus, Bergeyella, and Streptococcus and enrichment in periodontopathogens, especially Aa and sulfate reducing Deltaproteobacteria. The oral microbiome of the Aa JP2-like+ patient was phylogenetically distant from other GC/MIP individuals. GC/MIP presented a higher abundance of sulfidogenic bacteria in the feces, such as Desulfovibrio fairfieldensis, Erysipelothrix tonsillarum, and Peptostreptococcus anaerobius than controls. These preliminary data show that the dysbiosis of the microbiome in Afro-descendants with GC/MIP was not restricted to affected sites, but was also observed in supragingival and subgingival healthy sites, as well as in the feces. The understanding on differences of the microbiome between healthy and GC/MIP patients will help in developing strategies to improve and monitor periodontal treatment.

Tooth hypersensitivity is a common symptom in patients with molar-incisor hypomineralization (MIH). Therefore, this clinical study aimed to assess potential associations between patient- and tooth-related variables and the intensity of hypersensitivity in MIH-affected permanent teeth compared to healthy controls. Fifty-seven MIH patients and 20 healthy adolescents with a total of 350 MIH-affected and 193 healthy teeth were included in this study. The intensity of hypersensitivity was measured after cold air stimulation using the Schiff Cold Air Sensitivity Scale (SCASS) by the dentist and visual analogue scale (VAS) by the patient. Tooth hypersensitivity was low in non-MIH teeth (97.9% of the group had zero SCASS and VAS values). In contrast, MIH-affected teeth with demarcated opacities and atypical restorations had moderate SCASS and VAS values, whereas teeth with enamel breakdown were mostly linked to severe hypersensitivity. The logistic regression model confirmed a significantly lower level of hypersensitivity in MIH patients aged ≥ 8 years (OR 0.06, 95% CI 0.01-0.50, p = 0.009) and higher levels in molar teeth (OR 5.49, 95% CI 1.42-21.27, p = 0.014) and teeth with enamel disintegration (OR 4.61, 95% CI 1.68-12.63, p = 0.003). These results indicate that MIH-related tooth hypersensitivity seems to be present in disintegrated molars immediately after tooth eruption.

Molar incisor hypomineralization (MIH) is an endemic pediatric disease with an unclear pathogenesis. Considering that saliva controls enamel remineralization and that MIH is associated with higher saliva flow rate, we hypothesized that the protein composition of saliva is linked to disease. To test this, we enrolled 5 children aged 6-14 years with MIH showing at least one hypersensitive molar and 5 caries-free children without hypomineralization. Saliva samples were subjected to proteomic analysis followed by protein classification in to biological pathways. Among 618 salivary proteins identified with high confidence, 88 proteins were identified exclusively in MIH patients and 16 proteins in healthy controls only. Biological pathway analysis classified these 88 patient-only proteins to neutrophil-mediated adaptive immunity, the activation of the classical pathway of complement activation, extracellular matrix degradation, heme scavenging as well as glutathione -and drug metabolism. The 16 controls-only proteins were associated with adaptive immunity related to platelet degranulation and the lysosome. This report suggests that the proteaneous composition of saliva is affected in MIH patients, reflecting a catabolic environment which is linked to inflammation.

Molar incisor hypomineralization (MIH) frequently occurs in children worldwide. However, MIH prevalence throughout Japan has not yet been investigated. The purpose of this study was to clarify MIH prevalence rates and to consider potential regional differences throughout Japan.

Ectodysplasin (Eda) plays important roles in both shaping the developing tooth and establishing the number of teeth within the tooth row. Sonic hedgehog (Shh) has been shown to act downstream of Eda and is involved in the initiation of tooth development. Eda-/- mice possess hypoplastic and hypomineralized incisors and show changes in tooth number in the molar region. In the present study we used 3D reconstruction combined with expression analysis, cell lineage tracing experiments, and western blot analysis in order to investigate the formation of the incisor germs in Eda-/- mice. We show that a lack of functional Eda protein during early stages of incisor tooth germ development had minimal impact on development of the early expression of Shh in the incisor, a region proposed to mark formation of a rudimental incisor placode and act as an initiating signalling centre. In contrast, deficiency of Eda protein had a later impact on expression of Shh in the primary enamel knot of the functional tooth. Eda-/- mice had a smaller region where Shh was expressed, and a reduced contribution from Shh descendant cells. The reduction in the enamel knot led to the formation of an abnormal enamel organ creating a hypoplastic functional incisor. Eda therefore appears to influence the spatial formation of the successional signalling centres during odontogenesis.

Stem cells (SCs) receive inductive cues from the surrounding microenvironment and cells. Limited molecular evidence has connected tissue-specific mesenchymal stem cells (MSCs) with mesenchymal transit amplifying cells (MTACs). Using mouse incisor as the model, we discover a population of MSCs neibouring to the MTACs and epithelial SCs. With Notch signaling as the key regulator, we disclose molecular proof and lineage tracing evidence showing the distinct MSCs contribute to incisor MTACs and the other mesenchymal cell lineages. MTACs can feedback and regulate the homeostasis and activation of CL-MSCs through Delta-like 1 homolog (Dlk1), which balances MSCs-MTACs number and the lineage differentiation. Dlk1's function on SCs priming and self-renewal depends on its biological forms and its gene expression is under dynamic epigenetic control. Our findings can be validated in clinical samples and applied to accelerate tooth wound healing, providing an intriguing insight of how to direct SCs towards tissue regeneration.

Molar incisor hypomineralization (MIH) is a qualitative disturbance of the enamel of the permanent molars and/or incisors. Its etiology is not clearly defined but is connected with different factors occurring before and after birth. It remains difficult to identify a single factor or group of factors, and the problem is further complicated by various overlapping mechanisms. In this study, we attempted to determine whether DNA methylation-an epigenetic mechanism-plays a key role in the etiology of MIH. We collected the epithelium of the oral mucosa from children with MIH and healthy individuals and analyzed its global DNA methylation level in each child using a 5-mC DNA ELISA kit after DNA isolation. There was no statistically significant difference between the global DNA methylation levels in the study and control groups. Then, we also analyzed the associations of the DNA methylation levels with different prenatal, perinatal, and postnatal factors, using appropriate statistical methods. Factors such as number of pregnancies, number of births, type of delivery, varicella infection (under 3 years old), and high fever (under 3 years old) were significantly important. This work can be seen as the first step towards further studies of the epigenetic background of the MIH etiology.

Stem cell niches provide a microenvironment to support the self-renewal and multi-lineage differentiation of stem cells. Cell-cell interactions within the niche are essential for maintaining tissue homeostasis. However, the niche cells supporting mesenchymal stem cells (MSCs) are largely unknown. Using single-cell RNA sequencing, we show heterogeneity among Gli1+ MSCs and identify a subpopulation of Runx2+/Gli1+ cells in the adult mouse incisor. These Runx2+/Gli1+ cells are strategically located between MSCs and transit-amplifying cells (TACs). They are not stem cells but help to maintain the MSC niche via IGF signaling to regulate TAC proliferation, differentiation, and incisor growth rate. ATAC-seq and chromatin immunoprecipitation reveal that Runx2 directly binds to Igfbp3 in niche cells. This Runx2-mediated IGF signaling is crucial for regulating the MSC niche and maintaining tissue homeostasis to support continuous growth of the adult mouse incisor, providing a model for analysis of the molecular regulation of the MSC niche.

Our understanding of the initiation and cellular mechanisms underlying endochondral resorption of Meckel's cartilage (MC) remains limited. Several studies have shown that the resorption site of MC and the mandibular incisor tooth germ are located close to each other. However, whether incisor tooth germ development is involved in MC resorption remains unclear. In this study, we aimed to elucidate the spatio-temporal interaction between the initiation site of MC resorption and the development of incisor tooth germs in an embryonic mouse model. To this effect, we developed a histology-based three-dimensional (3D) reconstruction technique using paraffin-embedded serial sections of various tissues in the jaw. The serial sections were cut in the frontal section and the tissue constituents (e.g., MC, incisor, and mineralized mandible) were studied using conventional and enzyme-based histochemistry. The outline of each component was marked on the frontal sectional images and 3D structures were constructed. To assess the vascular architecture at the site of MC resorption, immunohistochemical staining using anti-laminin, anti-factor VIII, and anti-VEGF antibodies was performed. MC resorption was first observed on the lateral incisor-facing side of the cartilage rods at sites anterior to the mental foramen on E16.0. The 3D analysis suggested that: (a) the posterior region of the clastic cartilage resorption corresponds to the cervical loop of the incisor; (b) the cervical portion of the tooth germ inflates probably due to temporal cellular congestion prior to differentiation into matrix-producing cells; (c) the incisor tooth germ tissue is present in close proximity to MC even in mouse with continuously growing tooth and determines the disappearance of MC as the tooth development.

Cleft lip with or without cleft palate (CLP) is considered the most frequent congenital malformations of the head and neck, with cleft individuals exhibiting more chances of presenting abnormalities such as developmental defects of enamel (DDE). Matrix metallopeptidase 2 (MMP2) is a membrane-bound protein with collagen-degrading ability and has important roles in tooth formation and mineralization. The aim of this study was to evaluate the frequency, location, severity and extent of DDE found in the maxillary incisors for groups of individuals born with CLP, as well as understanding their relationship with the cleft side. Besides, this study addresses the hypothesis that DDE can be influenced by variation in the MMP2 genes (rs9923304). Individual samples, clinical history, intraoral photographs and panoramic radiographs were obtained from 233 patients under treatment at the Cleft Lip and Palate Service of the University Hospital Lauro Wanderley at the Federal University of Paraíba. Digital images were examined by the same evaluator using the Classification of Defects According to the Modified DDE Index, and then loaded into the Image Tool software, where two measurements were made: total area of the buccal surface (SA) and the area of the DDE (DA), obtaining the percentage of the surface area affected (%SAD) (ICC = 0.99). Genomic DNA was extracted from saliva samples from 124 participants. Genotyping was carried out using TaqMan chemistry for one marker in MMP2 (rs9923304). Statistical analyses were performed by The Jamovi Project software. The Shapiro-Wilk test was applied, followed by the Student's t-test and the Mann-Whitney test. Chi-square and Fisher's exact tests, and odds ratio (OR) with 95% confidence interval (CI) calculations were used to determine Hardy-Weinberg equilibrium and statistically significant differences with an alpha of 0.05. No significant differences in the prevalence and extent of enamel defects were found between male and female individuals born with CLP (p = 0.058256). The frequency of individuals presenting teeth with DDE, in relation to the cleft and non-cleft side, was statistically different (p <0.001; OR = 7.15, CI: 4.674> 7.151> 10.942). However, the averages of %SAD were similar (p = 0.18). The highest means of the %SAD were found in individuals with bilateral cleft lip with or without cleft palate (BCLP) when compared to individuals with unilateral cleft lip with or without cleft palate (UCLP), for the teeth inside (IA) and outside the cleft area (OA) (p <0.001). Regardless of the cleft side, individuals with BCLP were 7.85 times more likely to have more than one third of the tooth surface affected, showing more frequently defects in the three thirds (OA: p <0.001) (IA: p = 0.03), as well as a higher frequency of more than one type of defect (OA: p = 0.000358) (IA: p = 0.008016), whereas in UCLP, defects were isolated and restricted to only one third, more frequently, the incisal third (OA: p = 0.009) (IA: p = 0.001), with greater frequency of milder defects, such as demarcated (p = 0.02) and diffuse (p = 0.008) opacities. A higher frequency of the T allele, less common, was observed in the group of CLP individuals who had all the affected teeth or at least two teeth with %SAD greater than 20% (p = 0.019843). Our results suggest that MMP2 may have a role in the cases that presented DDE and genotyping rs9923304 could serve as the basis for a genomic approach to define risks for individuals born with CLP. Frequency and severity of DDE is strongly related to the CLP phenotype, since the highest values were found for BCLP. However, the extent of the DDE is independent of its relationship with the side of the cleft.

No abstract available