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Objectives: To explore the association between third molar agenesis and supernumerary tooth formation in a white‐European population. Materials and Methods: A record review in various orthodontic clinics identified 380 eligible white‐European individuals, half of whom had non‐syndromic permanent supernumerary teeth (122 males and 68 females, totalling 244 supernumerary teeth; median age: 13.1, iqr: 1.5 years), and the other half were age‐ and sex‐matched controls with full dentition, excluding the third molars. Tooth sequences were identified in panoramic radiographs. Results: In the supernumerary group, approximately 80% of the individuals had a single supernumerary tooth, followed by those having two additional teeth. In both groups, there was no sexual dimorphism in third molar agenesis severity. The prevalence of third molar agenesis in the supernumerary group was similar to that of the control group (28/190 = 14.7% in both groups; p = 1.0). In total, 53 third molars were missing in the supernumerary group (n = 190) compared to 67 in the control group (n = 190; p =.862). The ratio of bilateral to unilateral third molar agenesis was significantly lower in the supernumerary group than in the control group (1.0 vs. 3.7, respectively; p =.026). Conclusion: The presence of supernumerary teeth did not significantly alter the likelihood of third molar agenesis or its severity. Bilateral third molar agenesis was considerably less prevalent in individuals with supernumerary teeth compared to controls. The present novel findings have important clinical and developmental implications. [ABSTRACT FROM AUTHOR]

Novel methods and technologies that improve mesenchymal stem cells (MSCs) proliferation and differentiation properties are required to increase their clinical efficacy. Photobiomodulation (PBM) and low-intensity pulsed ultrasound (LIPUS) are two strategies that can be used to enhance the regenerative properties of dental MSCs. This study evaluated the cytocompatibility and osteo/odontogenic differentiation of dental pulp, periodontal ligament, and gingival MSCs after stimulation by either PBM or LIPUS and their combined effect. MTT assay, cell migration assay, osteo/odontogenic differentiation by AR staining and ALP activity, and expression of osteo/odontogenic markers (OPG, OC, RUNX2, DSPP, DMP1) by RT-qPCR were evaluated. Statistical analysis was performed using ANOVA, followed by Tukey's post hoc test, with a p-value of less than 0.05 considered significant. The results showed that combined stimulation by PBM and LIPUS resulted in significantly the highest viability of MSCs, the fastest migration, the most dense AR staining, the most increased ALP activity, and the most elevated levels of osteogenic and odontogenic markers. The synergetic stimulation of PBM and LIPUS can be utilized in cell-based regenerative approaches to promote the properties of dental MSCs. [ABSTRACT FROM AUTHOR]

The dental pulp is a highly innervated tissue transmitting pain‐related sensations in the tooth. Consequently, understanding the intricacies of its innervation mechanism in odontogenesis is crucial for gaining insights into dental pain and developing dental pain‐modulating agents. This study examined neuroregulatory molecules such as neurotrophic factors (nerve growth factor [NGF], brain‐derived neurotrophic factor [BDNF], neurotrophin‐4 [NTF‐4], and neurturin [NRTN]) and neuroinhibitory factors (slit2, ephrin isoforms and netrin‐1) in developing rat teeth with follicles. NGF, BDNF and NRTN transcriptions showed time‐dependent upregulation, particularly during the root formation stage. In contrast, NTF‐4 mRNA was highly expressed at the cap stage, but became downregulated over time. Slit2 and ephrin‐B2 expression was distinct at the cap stage and then downregulated in a time‐dependent manner. Ephrin‐A5 and netrin‐1 expression did not significantly change. Immunofluorescence analysis revealed a robust expression of both ephrin‐B2 and slit2 in the outer and inner dental epithelia of the enamel organ, a non‐neurogenic tissue, during the cap stage of 3rd molar germs. In contrast, BDNF was predominantly localized in dental papilla cells and odontoblasts during the root formation stage. These results suggest that neuroregulatory molecules, such as BDNF, slit2 and ephrin‐B2, may be important in identifying therapeutic targets for modulating dental pulp pain. [ABSTRACT FROM AUTHOR]

Objectives: A zinc‐finger transcription factor family comprising specificity proteins (SPs) and Krüppel‐like factor proteins (KLFs) plays an important role in dentin development and regeneration. However, a systematic regulatory network involving SPs/KLFs in odontoblast differentiation has not yet been described. This review examined the expression patterns of SP/KLF gene family members and their current known functions and mechanisms in odontoblast differentiation, and discussed prospective research directions for further exploration of mechanisms involving the SP/KLF gene family in dentin development. Materials and Methods: Relevant literature on SP/KLF gene family members and dentin development was acquired from PubMed and Web of Science. Results: We discuss the expression patterns, functions, and related mechanisms of eight members of the SP/KLF gene family in dentin development and genetic disorders with dental problems. We also summarize current knowledge about their complementary or synergistic actions. Finally, we propose future research directions for investigating the mechanisms of dentin development. Conclusions: The SP/KLF gene family plays a vital role in tooth development. Studying the complex complementary or synergistic interactions between SPs/KLFs is helpful for understanding the process of odontoblast differentiation. Applications of single‐cell and spatial multi‐omics may provide a more complete investigation of the mechanism involved in dentin development. [ABSTRACT FROM AUTHOR]

Objectives: Odontogenesis, an intricate process initiated by epithelium‐mesenchyme interaction, is meticulously regulated by a cascade of regulatory mechanisms. Epigenetic modifications, especially histone modification, have been found to exhibit spatiotemporal specificity during tooth development. However, the expression patterns and roles of enzymes associated with histone modifications have yet to be systematically explored in odontogenesis. This review aims to summarize the histone‐modifying enzymes in odontogenesis and their regulation mechanism during tooth development and provide the potential theoretical basis for the clinical management and intervention of dental developmental diseases. Subjects and Methods: This study conducted a systematic search across PubMed and Web of Science databases, utilizing the keywords "odontogenesis," "histone modification," and "enzyme" for pertinent articles. Results: No doubt histone modification contributes extensively to odontogenesis regulation, and the disturbances in histone modifications can derange the odontogenesis process. Conclusion: Further studies are warranted to elucidate these roles and their potential downstream effects, positioning histone modifications as a pivotal focal point for unraveling the intricacies of tooth development and regeneration. [ABSTRACT FROM AUTHOR]

The egg tooth of squamates is a true tooth that allows them to break, tear, or cut the eggshell during hatching. In this clade there are some uncertainties concerning the egg tooth implantation geometry, the number of germs, and their fates during embryonic development. Here, we used X-ray microtomography and light microscopy, focusing on the egg tooth and remaining premaxillary teeth of the sand lizard (Lacerta agilis , Squamata: Unidentata). The developing egg tooth of this species passes through all the classic stages of tooth development. We did not find any evidence that the large size of the egg tooth is related to the merging of two egg tooth germs, which has recently been suggested to occur in snakes. Instead, this feature can be attributed to the delayed formation of the neighbouring regular premaxillary teeth. This might provide more resources to the developing egg tooth. At the last developmental stage, the egg tooth is a large, midline structure, bent forward as in most oviparous Unidentata. It is characterized by pleurodont implantation, and its base is attached to the pleura and a peculiar ridge of the alveolar bone. The attachment tissue contains periodontal ligament-like tissue, acellular cementum-like tissue, and alveolar bone. [ABSTRACT FROM AUTHOR]

IntroductionThe regeneration of pulp tissue is crucial for true regenerative endodontic treatment, which requires a reduction in osteogenic differentiation. Garcinol, a histone acetyltransferase inhibitor, is a natural regulator that is known to suppress the osteogenic differentiation of dental pulp stem cells. In this study, the inhibitory effect of garcinol on the osteogenic differentiation of human dental pulp stem cells (hDPSCs) was evaluated using three-dimensional culture under in vitro and in vivo conditions.MethodshDPSCs were obtained from caries-free third molars and cultured with 10 μM garcinol for 7 days in an ultra-low attachment plate. The cell stemness and expression of osteogenic differentiation-related genes were analyzed using reverse transcription-polymerase chain reaction and single-cell analysis. A transplantation experiment was performed in mice to investigate whether garcinol-treated hDPSCs showed restrained osteogenic differentiation.ResultshDPSCs cultured in the U-shaped ultra-low attachment plate showed the highest expression of stemness-related genes. Garcinol-treated hDPSCs demonstrated downregulation of osteogenic differentiation, with lower expression of bone sialoprotein, which is related to bone formation, and higher expression of dentin sialophosphoprotein, which is related to dentin formation. However, the garcinol-treated hDPSCs did not show any alterations in their stemness. Consistent results were observed in the transplantation experiment in mice.ConclusionsGarcinol reduced the osteogenic differentiation of hDPSCs, which can contribute to true regenerative endodontic treatment.

Komal Smriti,1,* Murali Venkata Rama Mohan Kodali,2 Mathangi Kumar,1,* Anoushka Saraf,1 Medhini Madi,1 Kalyana Chakravarthy Pentapati,3 Prakashini K,4 Yogesh Chhaparwal,1 Unati Sai Kodali,5 Srikanth Gadicherla6 1Department of Oral Medicine & Radiology, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India; 2Department of Oral and Maxillofacial surgery, College of Dentistry, King Faisal University, Al Hofuf, Eastern Province-Al Ahsa, 31982, Kingdom of Saudi Arabia; 3Department of Public Health Dentistry, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104 India; 4Department of Radio Diagnosis, Kasturba Medical College & Hospital, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India; 5Dr Pinnamaneni Siddhartha Institute of Medical Sciences & Research Foundation, Dr. NTR University of Health Sciences, Vijayawada, India; 6Department of Oral & Maxillofacial Surgery, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India*These authors contributed equally to this workCorrespondence: Medhini Madi; Yogesh Chhaparwal, Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India, Email medhini.madi@manipal.edu; yogesh.chhaparwal@manipal.eduIntroduction: Dental age estimation using third molars is a reliable method for estimating the age of individuals. Recently, magnetic resonance imaging (MRI) of the head and neck has been found to be applicable for age estimation of third molar teeth. In the present study, we aimed to apply the Modified Demirjian method of age estimation to magnetic resonance (MR) image sections for dental age estimation by determining the mineralization patterns of the maxillary third molars.Methods: MRI scans of the patients were performed using SIGNA™ 3.0Tesla MRI GE Healthcare (Chicago, USA) with a moving, multifunctional coil. Two expert radiologists with more than three years of experience independently analyzed the image sections using the open-source Digital Imaging and Communications in Medicine (DICOM) viewer software. The age and sex of the patients whose images were included in the study were recorded using a specially designed proforma. The stage of development of the maxillary third molars was determined using the modified Demirjian method. Inter observer agreement was calculated using the intra class correlation coefficient. Simple linear regression analysis was used to predict the actual age at the third molar development stage.Results: There was excellent agreement between observers (ICC =0.99 (95% CI = 0.98– 0.99)). There was also a significant association between the maxillary third molar tooth development stage and chronological age of the individual (P=0.001; B=1.54; 95% CI = 0.71– 2.37).Discussion: The findings from the present study establish that the Modified Demirjian method can also be reliably applied for dental age assessment in MR sections.Keywords: third molars, forensic science, age estimation by teeth, odontogenesis

Background/purpose: Tooth development, or odontogenesis, is a complex process in which several molecular pathways play a key role. Recently, microRNAs, a class of approximately 20-nucleotide small RNA molecules that regulate gene expression, have been implicated in the odontogenesis process. This study aimed to assess the role of miRNAs in odontogenesis anomalies, specifically agenesis and impaction. Materials and methods: We analyzed a manually curated list of 82 miRNAs associated with human odontogenesis, sourced from literature data. Employing two different approaches to validate findings, we conducted functional enrichment analysis to evaluate the cell pathways, diseases, and phenotypes enriched for those miRNAs. Results: Our findings indicate that the analyzed miRNAs regulate pathways linked to tooth anomalies, including the TGFꞵ and Wnt signaling pathways, and those governing the pluripotency of stem cells, known to mediate various cellular processes, and interconnected with odontogenesis-related pathways. Furthermore, the analysis disclosed several pathways associated with tumors, including small cell lung and gastric cancer. These results were confirmed also by diseases and phenotypes enrichment evaluation. Moreover, cell network analysis disclosed that miRNAs are embedded and interconnected in networks associated with dental diseases and cancer development, thus confirming the functional enrichment analyses. Conclusion: In summary, our results offer a quantitative measure of the potential involvement of miRNAs in regulating pathways crucial for developmental processes, notably odontogenesis, and provide results suggesting potential association with oncogenesis processes as well.

The chronological age estimation of living individuals is a crucial part of forensic practice and clinical practice, such as in orthodontic treatment. It is well-known that methods for age estimation in living children should be tested on different populations. Ethnic affiliations in Brazil are divided into several major groups depending on the region, with the south of Brazil being known for its German immigration. (1) Background: This study aimed to evaluate the correlation between chronological age and dental age using Demirjian's method and Cameriere's method in a group of children from Joinville, South Brazil to investigate if both methods can be used to estimate dental age in this population. (2) Methods: The sample consisted of 229 panoramic radiographs (119 were males and were 110 females) from Brazilian children (ages ranging from 6 to 12 years). The chronological age at the time of the panoramic radiographic exam was calculated for each child. The dental age was estimated according to Demirjian's method and Cameriere's method. All continuous data were tested for normality by using the Shapiro–Wilk test. The Pearson correlation coefficient test was applied. An alpha of 5% (p < 0.05) was used for all analyses. (3) Results: The mean chronological age was 8.75 years. According to Demirjian's method, the mean dental age was 9.3 years, while according to Cameriere's method, the mean dental age was 8.66 years. A strong correlation between chronological age and dental age according to Demirjian (r = 0.776 and p < 0.0001) and Cameriere (r = 0.735 and p < 0.0001) was observed for both genders. (4) Conclusions: Both methods presented a good correlation with chronological age in the studied population and could be used to assess dental age in this population. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the impact of birth weight on tooth development in children aged 7–8 years. Materials and methods: This retrospective cohort study comprised 75 children born at Bint Al-Huda Hospital, Bojnurd, in 2013–2014. The children were categorized into three groups based on their birth weight: Normal Birth Weight (NBW), Low Birth Weight (LBW), and Very Low Birth Weight (VLBW). Panoramic radiographs were taken for orthodontic examination, and Demirjian’s 8-teeth method was employed to determine dental age. The study compared dental and chronological age within each group. Data analysis utilized SPSS software version 26, employing One-way ANOVA and chi-square tests. Statistical significance was set at P ≤ 0.05. Results: The mean difference in dental and chronological age for Very Low Birth Weight (VLBW) children was 0.22 ± 0.44 years, for Low Birth Weight (LBW) children it was 0.19 ± 0.45 years, and for Normal Birth Weight (NBW) children, it was 0.08 ± 0.46 years. Although the mean difference decreased with increasing birth weight, this trend did not achieve statistical significance (P = 0.55). Furthermore, no significant differences were observed between the weight groups (P = 0.529) or genders (P = 0.191). [ABSTRACT FROM AUTHOR]

Ameloblastoma is a non-cancerous but aggressive oral tumor emerging from odontogenic epithelial tissue involved during odontogenesis. Since there is lack in unravelling the complete molecular pathogenesis of ameloblastoma, chemotherapy is less attempted and a lot of disagreement over the optimal treatment option. Hence, till date, wide surgical resection is considered to be the reliable treatment for ameloblastoma. The Neurotrophin Signaling pathway plays an important role in neuron signaling and it is closely related with the MAPK pathway, which on the other hand regulated cell differentiation, apoptosis, proliferation, plasticity and survival. Protein- Protein Interaction analysis was analysed with STRING tool using WNL value, identified that CTNNB1, HRAS, NGFR, NGFR, and SORT1 having high interacting with BDNF, NT4, p75NTR, NGF, and NT3. The results of ontology analysis revealed that Neurotrophin signaling pathway is associated with Cell surface receptor signaling pathway, regulation of cell differentiation, regulation of development process, EGFR tyrosine kinase inhibitor resistance, MAPK signaling pathway, PI3K-Akt signaling pathway and Ras signaling pathway leading to pathogenesis involving genes. Further, clustering coefficient values of proteins BDNF, NT4, p75NTR, NGF & NT3 were identified as 0.627, 0.708, 0.367, 0.644 & 0.415. The results of molecular docking studies revealed among the selected ligands Methyl-ɣ-oresellinate, N-(4-Hydroxy-phenyl)-2-phenyl-N-phenylacetyl-acetamide, Atranorin and Oresellinate exhibited high binding affinity with selected protein. The key genes involved in Neurotrophin signaling pathway leading to ameloblastoma pathogenesis is revealed, which are closely associated with cell differentiation, cell proliferation, pro-apoptosis, and pro-survival regulations. Further it can be concluded that Neurotrophin signaling pathway could be one of the promising pathway to tailor the targeted drug therapy for Ameloblastoma treatment. [ABSTRACT FROM AUTHOR]

Mineral trioxide aggregate (MTA) is a biomaterial used in endodontics due to its high bioactivity, antibacterial behaviors, and good biocompatibility. However, it has several disadvantages related to certain physical properties, including a long setting time and poor mechanical properties. Therefore, we hypothesized that coating MTA with gallic acid (GA) would regulate physical properties and lead to enhanced adhesion, proliferation, and secretion of angiogenic- and odontogenic-related proteins. This study examined whether MTA can be modified with GA to form GAMTA cement and evaluated its physicochemical and biological behaviors and immune suppression, angiogenesis, and odontogenesis capabilities. We soaked MTA in Tris buffer containing different concentrations of GA to coat the MTA powders. X-ray diffraction (XRD) and diametral tensile strength analyses were conducted to assess the physical characteristics of GAMTA. Then, we immersed GAMTA cement in simulated body fluid to evaluate its hydroxyapatite precipitation capabilities and silicon ion release profile. We used human dental pulp stem cells to assess the cell responses and the immunosuppressive, angiogenic, and odontogenic capabilities of GAMTA. The XRD results showed that GA was successfully coated onto MTA without the disruption or loss of MTA's advantageous original structural properties. GAMTA demonstrated excellent physicochemical and biological properties, improving hydroxyapatite formation and angiogenic, odontogenic, and anti-inflammatory properties compared with MTA alone. Our results indicate that the GAMTA cement is a useful dental material for future tissue engineering and clinical applications. [ABSTRACT FROM AUTHOR]

Introduction and purpose: Hypodontia and hyperdontia are two common developmental dental anomalies characterized by an abnormal number of teeth and they present a significant challenge in dentistry, affecting both the functionality and aesthetics of the dentition. Hypodontia refers to the congenital absence of one or more teeth, while hyperdontia is characterized by the presence of supernumerary teeth in the oral cavity. These conditions can lead to various complications, such as bite issues, speech disorders, and difficulties in daily functioning. State of knowledge: Tooth number anomalies can have various causes, ranging from evolutionary reduction in dentition due to lifestyle changes over the years. The reduction in the number of teeth is currently among the most common developmental dental defects. Environmental factors also influence tooth number, acting as either local or general factors. Genetic influences should also be considered, as hypodontia and hyperdontia can be hereditary, and gender also plays a role in the predisposition to these conditions. Numerical anomalies in teeth can also be a symptom of certain genetically determined syndromes. Summary: Hypodontia and hyperdontia are examples of developmental disorders related to the number of teeth in the oral cavity, with various underlying causes. Diagnosis and subsequent treatment are crucial in managing these conditions. These disorders may require long-term therapies involving different areas of dentistry and interdisciplinary cooperation or may simply require ongoing clinical and radiological observation. Treatment depends on the severity of the disorder and the individual needs of the patient. However, thanks to advances in diagnosis and treatment, it is possible to effectively prevent complications.

Preserving vital pulp in cases of dental pulpitis is desired but remains challenging. Previous research has shown that bioactive glass (BG) possesses notable capabilities for odontogenic differentiation. However, the immunoregulatory potential of BG for inflamed pulp is still controversial, which is essential for preserving vital pulp in the context of pulpitis. This study introduces a novel approach utilizing polydopamine-coated BG (BG-PDA) which demonstrates the ability to alleviate inflammation and promote odontogenesis for vital pulp therapy. In vitro, BG-PDA has the potential to induce M2 polarization of macrophages, resulting in decreased intracellular reactive oxygen species levels, inhibition of pro-inflammatory factor, and enhancement of anti-inflammatory factor expression. Furthermore, BG-PDA can strengthen the mitochondrial function in macrophages and facilitate odontogenic differentiation of human dental pulp cells. In a rat model of pulpitis, BG-PDA exhibits the capacity to promote M2 polarization of macrophages, alleviate inflammation, and facilitate dentin bridge formation. This study highlights the notable immunomodulatory and odontogenesis-inducing properties of BG-PDA for treating dental pulpitis, as evidenced by both in vitro and in vivo experiments. These results imply that BG-PDA could serve as a promising biomaterial for vital pulp therapy.

Changes in the expression of nuclear β‐catenin are responsible for tumorigenesis. Beta‐catenin acts synergistically with the TGF‐β/BMPs pathway. This interaction leads to greater dentin deposition and may explain the differences between distinct tooth morphologies and hamartomas. The aim of this study was to investigate the role of β‐catenin, BMP4 and TGF‐β in the development of odontomas. This cross‐sectional, retrospective, immunohistochemical study evaluated 30 compound odontomas, 30 complex odontomas and 17 tooth germs. The results showed that BMP4 and TGF‐β were more immunoexpressed in the ectomesenchyme of complex odontomas (median = 33.7, p < 0.001; median = 76.4, p = 0.002, respectively). Higher immunoexpression of BMP4 and TGF‐β was also observed in the epithelium of tooth germs (median = 2.0, p < 0.001; median = 120.3, p < 0.001, respectively). TGF‐β and BMP4 showed a positive and significant correlation (p < 0.001). Both TGF‐β and BMP4 were positively correlated with nuclear β‐catenin in ectomesenchyme (p = 0.047 and p = 0.023, respectively). Developing teeth exhibited higher concentrations of the proteins studied in odontogenic epithelium, especially during the bud and cap stages. Higher immunoexpression in odontomas occurred mainly in the ectomesenchyme. We therefore suggest that changes in the ectomesenchyme can lead to the development of odontomas. [ABSTRACT FROM AUTHOR]

The current study used a three-dimensional (3D) surface homologous modeling to analyze the structure of maxillary first premolar (P1) and second premolar (P2) crowns, to identify any morphological differences between them, particularly in their cuspal structures. The study sample comprised 27 male elementary and junior high school students from Chiba Prefecture, Japan. Plaster casts were collected and the 3D coordinates were used to measure the crown structures. Thereafter, principal component (PC) analysis was carried out using the 3D coordinates of the homologous models, containing 4498 anatomical data points, including 9 landmarks. The findings indicated that P1 was significantly larger than P2, despite both teeth exhibiting similar intercuspal distances. The homologous model analysis revealed that 61.5 % of the total variance could be explained up to the fourth PC. Overall size and shape in the mesiodistal and buccolingual directions were estimated using PC1 and PC2, respectively. Both components highlighted a shape factor, indicating that the buccal cusp was more well-developed than the lingual cusp in P1 compared to P2. The variations in the size of the mesial and distal premolar teeth and the relationships between the cusps in the completed tooth crowns can be explained using molecular biology developmental models. [Display omitted] • 3D surface structures of the maxillary first and second premolars were analyzed. • The crown structures were analyzed based on the 3D coordinates of landmarks. • 3D surface crown structures were analyzed using a homologus modeling. • The interrelationships between cusps were discussed using developmental models. [ABSTRACT FROM AUTHOR]

Maxillary first premolars have a unique shape because of their curvature features, positional relationship of the cusps, and most prominent points, making them different from other teeth. This study aimed to quantitatively analyze the detailed three-dimensional morphometric structure of maxillary first premolars and sexual dimorphism. The study participants were 60 elementary and junior high school students (30 boys and 30 girls) in Japan. The distance between landmarks was measured using the three-dimensional coordinates of plaster casts, and the data collected was statistically analyzed. Sexual dimorphism was greater in the lingual cusp, showing greater variation in size than the buccal cusp. Boys exhibited significantly larger relative distances in the mesiodistal and buccolingual directions than girls; particularly, regarding mesiodistal diameter of the central groove, mesial slope of the buccal cusp, and distal slope of the lingual cusp. These results may be due to a slight difference in the timing of secondary enamel knots between boys and girls during the developmental stage, which was reflected in the sexual dimorphism of the completed teeth. Curvature features, cusp positions, and most prominent points were considered individual traits because they were not interrelated. Subtle differences during the developmental stage may lead to sexual dimorphism of the completed crown. Furthermore, the morphological characteristics of the maxillary first premolars may be related to their location in the dental arch. [ABSTRACT FROM AUTHOR]

Studies on odontogenesis are of great importance to treat dental abnormalities and tooth loss. However, the odontogenesis process was poorly studied in humans, especially at the early developmental stages. Here, we combined RNA sequencing (RNA-seq) with Laser-capture microdissection (LCM) to establish a spatiotemporal transcriptomic investigation for human deciduous tooth germs at the crucial developmental stage to offer new perspectives to understand tooth development and instruct tooth regeneration. Several hallmark events, including angiogenesis, ossification, axonogenesis, and extracellular matrix (ECM) organization, were identified during odontogenesis in human dental epithelium and mesenchyme from the cap stage to the early bell stage. ECM played an essential role in the shift of tooth-inductive capability. Species comparisons demonstrated these hallmark events both in humans and mice. This study reveals the hallmark events during odontogenesis, enriching the transcriptomic research on human tooth development at the early stage.

Ameloblastic carcinoma is a malignant odontogenic neoplasm that has been reported only rarely in veterinary species. A 16-y-old Arabian crossbred mare was presented for evaluation of a hard mass on the body of the mandible, with evidence of osteolysis on radiographs. Incisional biopsies revealed an invasive neoplasm comprised of spindloid epithelial cells with a high mitotic count and partial dual cytokeratin-vimentin immunoreactivity. The horse was euthanized because of rapid tumor progression 3 mo after presentation. Postmortem evaluation revealed partial obliteration of the mandible by a large, firm-to-hard, tan, locally destructive and invasive mass with no gross or histologic evidence of metastasis. Postmortem histology revealed a poorly differentiated epithelial neoplasm with variably prominent features suggestive of odontogenic histogenesis: a plexiform ribbon architecture, infrequent basilar palisading with antibasilar nuclei, rare basilar cytoplasmic clearing, subepithelial matrix hyalinization, and partial dual cytokeratin-vimentin immunoreactivity. Features of malignancy included regions of necrosis, pronounced cellular atypia, a high mitotic count, extensive tissue invasion and local tissue destruction, and extension of neoplastic cells beyond the margins of the mandibular bone. Collectively, these features are most consistent with mandibular ameloblastic carcinoma. Including our case described here, ameloblastic carcinoma has been reported in only 5 horses. The microscopic features reported most consistently are dual cytokeratin-vimentin immunoreactivity, a high mitotic count, and basilar palisading. Ameloblastic carcinoma should be considered as a differential diagnosis for rapidly growing, locally invasive masses arising from the dentate jaw of horses.

Glomerular epithelial protein-1 (Glepp1), a R3 subtype family of receptor-type protein tyrosine phosphatases, plays important role in the activation of Src family kinases and regulates cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, we firstly examined the functional evaluation of Glepp1 in tooth development and morphogenesis. The precise expression level and developmental function of Glepp1 were examined by RT-qPCR, in situ hybridization, and loss and gain of functional study using a range of in vitro organ cultivation methods. Expression of Glepp1 was detected in the developing tooth germs in cap and bell stage of tooth development. Knocking down Glepp1 at E13 for 2 days showed the altered expression levels of tooth development-related signaling molecules, including Bmps, Dspp, Fgf4, Lef1, and Shh. Moreover, transient knock down of Glepp1 revealed alterations in cellular physiology, examined by the localization patterns of Ki67 and E-cadherin. Similarly, knocking down of Glepp1 showed disrupted enamel rod and interrod formation in 3-week renal transplanted teeth. In addition, due to attrition of odontoblastic layers, the expression signals of Dspp and the localization of NESTIN were almost not detected after knock down of Glepp1; however, their expressions were increased after Glepp1 overexpression. Thus, our results suggested that Glepp1 plays modulating roles during odontogenesis by regulating the expression levels of signaling molecules and cellular events to achieve the proper structural formation of hard tissue matrices in mice molar development. [ABSTRACT FROM AUTHOR]

Copyright of Brazilian Dental Science is the property of Brazilian Dental Science Journal-ICT-UNESP and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Stomatologica Croatica is the property of Acta Stomatologica Croatica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The variability in tooth crown size (TCS) is influenced by genetic factors and might be regulated by the difference in hormonal response. Materials and Methods: This study aimed to evaluate the association between variations in TCS of permanent teeth with associated factors and genetic polymorphisms in hormonal‐related genes (ESR1, ESR2 and PTH). This cross‐sectional study involved dental casts from 86 individuals of both sexes. Dental casts were used to determine the maximum TCS of all fully erupted permanent teeth (except third molars) in the mesiodistal (MD) and buccolingual (BL) dimensions. Data such as sex, ethnicity, dental group (incisor, canine, premolar and molar), dental arch (upper and lower) and genetic polymorphisms of hormonal‐related genes were used. The DNA from each patient was collected to evaluate the genetic polymorphisms in ESR1 (rs2234693 and rs9340799), ESR2 (rs1256049 and rs4986938) and PTH (rs694, rs6256 and rs307247) through real‐time PCR. The data were submitted to statistical analysis with a significance level of 0.05. Results: In the MD dimension, the sex, dental group and dental arch were associated with variation in TCS (P <.05). In the BL dimension, the sex, dental group, dental arch and polymorphism in rs694 and rs307247 were associated with variation in TCS. Conclusions: In short, this study suggests that genetic polymorphisms of PTH are associated with variations in the BL TCS of permanent human teeth. [ABSTRACT FROM AUTHOR]

Abstract Background CDC42 is a member of Rho GTPase family, acting as a molecular switch to regulate cytoskeleton organization and junction maturation of epithelium in organ development. Tooth root pattern is a highly complicated and dynamic process that dependens on interaction of epithelium and mesenchyme. However, there is a lack of understanding of the role of CDC42 during tooth root elongation. Methods The dynamic expression of CDC42 was traced during tooth development through immunofluorescence staining. Then we constructed a model of lentivirus or inhibitor mediated Cdc42 knockdown in Herwig’s epithelial root sheath (HERS) cells and dental papilla cells (DPCs), respectively. Long-term influence of CDC42 abnormality was assessed via renal capsule transplantation and in situ injection of alveolar socket. Results CDC42 displayed a dynamic spatiotemporal pattern, with abundant expression in HERS cells and apical DPCs in developing root. Lentivirus-mediated Cdc42 knockdown in HERS cells didn’t disrupt cell junctions as well as epithelium-mesenchyme transition. However, inhibition of CDC42 in DPCs undermined cell proliferation, migration and odontogenic differentiation. Wnt/β-catenin signaling as the downstream target of CDC42 modulated DPCs’ odontogenic differentiation. The transplantation and in situ injection experiments verified that loss of CDC42 impeded root extension via inhibiting the proliferation and differentiation of DPCs. Conclusions We innovatively revealed that CDC42 was responsible for guiding root elongation in a mesenchyme-specific manner. Furthermore, CDC42-mediated canonical Wnt signaling regulated odontogenic differentiation of DPCs during root formation.

Statement of the Problem: Enamel organ (EO) is an ectodermal derived structure, which is involved in the different aspects of tooth development. Tooth development shares the same regulatory molecules and genes expressed in other developing organs. Endothelin- 1 (ET-1) and Endothelin A receptor (ETAR), (ET-1/ETAR) axis, are involved in differentiation of embryonic stem cells and organ development.Purpose: The present study aimed to investigate the ET-1 and ETAR expression profiles during the development of human primary tooth EO with the relatively large sample size.Materials and Method: In this experimental study, 33 human fetuses aged from 13 to 23 weeks (3 samples from each fetal age) were collected. The samples were divided into three age groups (

Abstract Objectives Molar-root incisor malformation (MRIM) is a seldom reported condition characterised by disturbances in root development of first permanent molars. This systematic review aimed to collate the clinical characteristics of individuals diagnosed with MRIM. Materials and methods A systematic search strategy using PubMed, Embase, Web of Science, and SCOPUS databases was performed through to March 2023. Inclusion criteria were case reports or case series including a diagnosis consistent with MRIM. Critical appraisal for all included studies utilised the Joanna Briggs Institute (JBI) critical appraisal checklist for case reports and case series and collation of clinical characteristics was performed in JBI System for the Unified Management, Assessment and Review of Information program. Results The search identified 157 studies from which 35 satisfied the inclusion criteria. After full-text review, a total of 23 papers described the MRIM dental anomaly and were included in this paper. A total of 130 reported cases were retrieved, with age ranging 3–32 years, and males affected 1.16:1 females. Presence of neurological conditions, premature birth history, medication, and surgery within first years of life were synthesised and described. Conclusions The aetiology of MRIM is yet to be determined but epigenetic changes from significant medical history in the first years of life are likely to influence the development of this root malformation. First permanent molars were most commonly affected, but clinicians should be aware that permanent central incisors, primary teeth and other permanent teeth may also be affected.

The chronological age estimation of living individuals is a crucial part of forensic practice and clinical practice, such as in orthodontic treatment. It is well-known that methods for age estimation in living children should be tested on different populations. Ethnic affiliations in Brazil are divided into several major groups depending on the region, with the south of Brazil being known for its German immigration. (1) Background: This study aimed to evaluate the correlation between chronological age and dental age using Demirjian’s method and Cameriere’s method in a group of children from Joinville, South Brazil to investigate if both methods can be used to estimate dental age in this population. (2) Methods: The sample consisted of 229 panoramic radiographs (119 were males and were 110 females) from Brazilian children (ages ranging from 6 to 12 years). The chronological age at the time of the panoramic radiographic exam was calculated for each child. The dental age was estimated according to Demirjian’s method and Cameriere’s method. All continuous data were tested for normality by using the Shapiro–Wilk test. The Pearson correlation coefficient test was applied. An alpha of 5% (p < 0.05) was used for all analyses. (3) Results: The mean chronological age was 8.75 years. According to Demirjian’s method, the mean dental age was 9.3 years, while according to Cameriere’s method, the mean dental age was 8.66 years. A strong correlation between chronological age and dental age according to Demirjian (r = 0.776 and p < 0.0001) and Cameriere (r = 0.735 and p < 0.0001) was observed for both genders. (4) Conclusions: Both methods presented a good correlation with chronological age in the studied population and could be used to assess dental age in this population.

Background: Tooth development involves reciprocal interactions between the oral epithelium and ectomesenchyme. The inner layer cells of the enamel organ (EO), known as the inner enamel epithelium (IEE), undergo differentiation into preameloblasts and subsequently mature ameloblasts. These ameloblasts play a crucial role in the secretion of enamel matrix proteins, including amelogenin. This experimental study aimed to analyze the expression profile of amelogenin in various histological structures of human primary developing teeth, employing a relatively large sample size. Methods: This experimental study included 33 human fetuses aged between 13 and 23 weeks, with three samples obtained from each gestational age. The samples were categorized into three age groups of ≥13 and

Introduction and aim: Human dentition is an object of interest of both dentistry and dental anthropology, and a source of diverse information about human evolution, variability of populations, individual development or pathological cases. Both subjects often study the clinically visible result of phylogeny and ontogeny: a tooth crown. Tooth crown especially of the posterior dentition, i.e., premolars and molars, is characterized by complex morphology which is formed by iterative processes of genetic, epigenetic, and environmental character. After its completion, a tooth crown can be altered only by destruction of hard tissues, e.g., dental caries, trauma or tooth wear. Size and shape of tooth crown is traditionally studied by linear dimensions or by observation and scoring of the discrete morphological traits. With the expansion of modern imaging technologies, new methodological approaches are used increasingly. These approaches are more suitable for describing the variation of dentition and their results are potentially more informative about the biological basis of dental variability. The aim of this study is to describe and summarize the current trends of tooth morphology quantification in dental anthropology. Methods: Study was based on the survey of research papers and books focused on tooth morphology and approaches of dental anthropology to its study. Mostly the Web of Science and PubMed databases were used for the survey. Conclusion: The review is focused on the methods of quantification of human dental morphology and their use with respect to the development of tooth morphology.

Variation in tooth crown morphology plays a crucial role in species diagnoses, phylogenetic inference, and the reconstruction of the evolutionary history of the primate clade. While a growing number of studies have identified developmental mechanisms linked to tooth size and cusp patterning in mammalian crown morphology, it is unclear (1) to what degree these are applicable across primates and (2) which additional developmental mechanisms should be recognized as playing important roles in odontogenesis. From detailed observations of lower molar enamel–dentine junction morphology from taxa representing the major primate clades, we outline multiple phylogenetic and developmental components responsible for crown patterning, and formulate a tooth crown morphology framework for the holistic interpretation of primate crown morphology. We suggest that adopting this framework is crucial for the characterization of tooth morphology in studies of dental development, discrete trait analysis, and systematics. [ABSTRACT FROM AUTHOR]

Tooth gemination is a dental anomaly that results from an incomplete attempt of a single tooth germ to separate during morphodifferentiation stage of odontogenesis, and it usually exhibits a large bifid crown with a single common root and root canal. This developmental anomaly more commonly affects primary dentition than the permanent, with an infrequent occurrence reported of posterior teeth. Among the posterior teeth, mandibular second premolars have reportedly shown an elevated possibility of agenesis, delayed odontogenesis, and variability of crown morphology. Both unilateral and bilateral cases of isolated macrodontia of mandibular second premolar secondary to gemination or fusion have been reported, but there is no evidence of microdontia associated with gemination in the literature till date. This case presentation reports an unusual case of isolated unilateral gemination-associated microdontia of the left mandibular second premolar in a nonsyndromic patient. [ABSTRACT FROM AUTHOR]

Supernumerary teeth form at an incidence of about 3% in the population, with differences among races and various clinical consequences. Information on detailed patterns, and especially on white subjects, is scarce in the literature. Therefore, we aimed to investigate the patterns of non-syndromic permanent supernumerary teeth in a white European population. A record review was performed in different orthodontic clinics and identified 207 eligible individuals with 258 supernumerary teeth. Approximately 80% of the subjects had one supernumerary tooth, while 15% had two. Supernumerary tooth formation was more often evident in males (male/female: 1.65). However, there was no sexual dimorphism in its severity. The following pattern sequences, with decreasing prevalence order, were observed in the maxilla: 21 > 11 > 12 > 18 > 28 and in the mandible: 34 > 44 > 35 > 45 > 42. Supernumerary teeth were most often unilaterally present, without sexual dimorphism. In the maxilla, they were more often anteriorly present, whereas in the mandible, an opposite tendency was observed. Supernumerary teeth were consistently more often observed in the maxilla than in the mandible; 74% were impacted, 80% had normal orientation (13% horizontal, 7% inverted), and 53% had normal size. The present thorough supernumerary tooth pattern assessment enables a better understanding of this condition with clinical, developmental, and evolutionary implications. [ABSTRACT FROM AUTHOR]

Background: CDC42 is a member of Rho GTPase family, acting as a molecular switch to regulate cytoskeleton organization and junction maturation of epithelium in organ development. Tooth root pattern is a highly complicated and dynamic process that dependens on interaction of epithelium and mesenchyme. However, there is a lack of understanding of the role of CDC42 during tooth root elongation. Methods: The dynamic expression of CDC42 was traced during tooth development through immunofluorescence staining. Then we constructed a model of lentivirus or inhibitor mediated Cdc42 knockdown in Herwig's epithelial root sheath (HERS) cells and dental papilla cells (DPCs), respectively. Long-term influence of CDC42 abnormality was assessed via renal capsule transplantation and in situ injection of alveolar socket. Results: CDC42 displayed a dynamic spatiotemporal pattern, with abundant expression in HERS cells and apical DPCs in developing root. Lentivirus-mediated Cdc42 knockdown in HERS cells didn't disrupt cell junctions as well as epithelium-mesenchyme transition. However, inhibition of CDC42 in DPCs undermined cell proliferation, migration and odontogenic differentiation. Wnt/β-catenin signaling as the downstream target of CDC42 modulated DPCs' odontogenic differentiation. The transplantation and in situ injection experiments verified that loss of CDC42 impeded root extension via inhibiting the proliferation and differentiation of DPCs. Conclusions: We innovatively revealed that CDC42 was responsible for guiding root elongation in a mesenchyme-specific manner. Furthermore, CDC42-mediated canonical Wnt signaling regulated odontogenic differentiation of DPCs during root formation. [ABSTRACT FROM AUTHOR]

In recent research, there has been a growing awareness of the role of genetic factors in the positioning and eruption of teeth in the maxilla and mandible. This study aimed to evaluate the potential of specific polymorphic markers of single nucleotide polymorphisms (SNPs) located within the PAX9, MSX1, AXIN2, and IRF6 genes to determine the predisposition to tooth impaction. The study participants were divided into two groups: the first group consisted of individuals with at least one impacted secondary tooth. In contrast, the second group (control group) had no impacted teeth in their jaws. To analyze the genes, real-time PCR (polymerase chain reaction) and TaqMan probes were utilized to detect the selected polymorphisms. The findings suggest that disruptions in the structure and function of the mentioned genetic factors such as polymorphic and haplotype variants of PAX9, MSX1, AXIN2, and IRF6 genes, which play a direct role in tooth and periodontal tissue development, might be significant factors in tooth impaction in individuals with genetic variations. Therefore, it is reasonable to hypothesize that tooth impaction may be influenced, at least in part, by the presence of specific genetic markers, including different allelic variants of the PAX9, AXIN2, and IRF6 genes, and especially MSX1. [ABSTRACT FROM AUTHOR]

Objective: Herein, we evaluated pinealectomy-induced melatonin absence to determine its effects on craniofacial and dental development in the offspring. Design: Female Wistar rats in three groups, i.e., intact pregnant rats, pinealectomized pregnant rats (PINX), and pinealectomized pregnant rats subjected to oral melatonin replacement therapy, were crossed 30 days after surgery. The heads of 7-day-old pups were harvested for cephalometric and histological analyses, and maxillae and incisors were collected for mRNA expression analysis. Results: The PINX pups exhibited a reduction in neurocranial and facial parameters such as a decrease in alveolar bone area, incisor size and proliferation, and an increase in odontoblasts and the dentin layer. Based on incisor mRNA expression analysis, we found that Dmp1 expression was upregulated, whereas Col1a1 expression was downregulated. Maxillary mRNA expression revealed that Rankl expression was upregulated, whereas that of Opn and Osx was downregulated. Conclusion: Our results demonstrated that the absence of maternal melatonin during early life could affect dental and maxillary development in offspring, as well as delay odontogenesis and osteogenesis in maxillary tissues. Clinical relevance: Our findings suggest that disruptions or a lack of melatonin during pregnancy may cause changes in craniofacial and dental development, at least in animal experiments; however, in humans, these feedings are still poorly understood, and thus careful evaluations of melatonin levels in humans need to be investigated in craniofacial alterations. [ABSTRACT FROM AUTHOR]

Objectives: Molar-root incisor malformation (MRIM) is a seldom reported condition characterised by disturbances in root development of first permanent molars. This systematic review aimed to collate the clinical characteristics of individuals diagnosed with MRIM. Materials and methods: A systematic search strategy using PubMed, Embase, Web of Science, and SCOPUS databases was performed through to March 2023. Inclusion criteria were case reports or case series including a diagnosis consistent with MRIM. Critical appraisal for all included studies utilised the Joanna Briggs Institute (JBI) critical appraisal checklist for case reports and case series and collation of clinical characteristics was performed in JBI System for the Unified Management, Assessment and Review of Information program. Results: The search identified 157 studies from which 35 satisfied the inclusion criteria. After full-text review, a total of 23 papers described the MRIM dental anomaly and were included in this paper. A total of 130 reported cases were retrieved, with age ranging 3–32 years, and males affected 1.16:1 females. Presence of neurological conditions, premature birth history, medication, and surgery within first years of life were synthesised and described. Conclusions: The aetiology of MRIM is yet to be determined but epigenetic changes from significant medical history in the first years of life are likely to influence the development of this root malformation. First permanent molars were most commonly affected, but clinicians should be aware that permanent central incisors, primary teeth and other permanent teeth may also be affected. [ABSTRACT FROM AUTHOR]

Development has often been viewed as a constraining force on morphological adaptation, but its precise influence, especially on evolutionary rates, is poorly understood. Placental mammals provide a classic example of adaptive radiation, but the debate around rate and drivers of early placental evolution remains contentious. A hallmark of early dental evolution in many placental lineages was a transition from a triangular upper molar to a more complex upper molar with a rectangular cusp pattern better specialized for crushing. To examine how development influenced this transition, we simulated dental evolution on "landscapes" built from different parameters of a computational model of tooth morphogenesis. Among the parameters examined, we find that increases in the number of enamel knots, the developmental precursors of the tooth cusps, were primarily influenced by increased self-regulation of the molecular activator (activation), whereas the pattern of knots resulted from changes in both activation and biases in tooth bud growth. In simulations, increased activation facilitated accelerated evolutionary increases in knot number, creating a lateral knot arrangement that evolved at least ten times on placental upper molars. Relatively small increases in activation, superimposed on an ancestral tritubercular molar growth pattern, could recreate key changes leading to a rectangular upper molar cusp pattern. Tinkering with tooth bud geometry varied the way cusps initiated along the posterolingual molar margin, suggesting that small spatial variations in ancestral molar growth may have influenced how placental lineages acquired a hypocone cusp. We suggest that development could have enabled relatively fast higher-level divergence of the placental molar dentition.

Abstract Background Epithelium-mesenchymal interactions are involved in odontogenic processes. Previous studies have focused on the intracellular signalling regulatory network in tooth development, but the functions of extracellular regulatory molecules have remained unclear. This study aims to explore the gene profile of extracellular proteoglycans and their glycosaminoglycan chains potentially involved in dental epithelium-mesenchymal interactions using high-throughput sequencing to provide new understanding of early odontogenesis. Results Whole transcriptome profiles of the mouse dental epithelium and mesenchyme were investigated by RNA sequencing (RNA-seq). A total of 1,281 and 1,582 differentially expressed genes were identified between the dental epithelium and mesenchyme at E11.5 and E13.5, respectively. Enrichment analysis showed that extracellular regions and ECM-receptor interactions were significantly enriched at both E11.5 and E13.5. Polymerase chain reaction analysis confirmed that the extracellular proteoglycan family exhibited distinct changes during epithelium-mesenchymal interactions. Most proteoglycans showed higher transcript levels in the dental mesenchyme, whereas only a few were upregulated in the epithelium at both stages. In addition, 9 proteoglycans showed dynamic expression changes between these two tissue compartments. Gpc4, Sdc2, Spock2, Dcn and Lum were expressed at higher levels in the dental epithelium at E11.5, whereas their expression was significantly higher in the dental mesenchyme at E13.5, which coincides with the odontogenic potential shift. Moreover, the glycosaminoglycan biosynthetic enzymes Ext1, Hs3st1/5, Hs6st2/3, Ndst3 and Sulf1 also exhibited early upregulation in the epithelium but showed markedly higher expression in the mesenchyme after the odontogenic potential shift. Conclusion This study reveals the dynamic expression profile of extracellular proteoglycans and their biosynthetic enzymes during the dental epithelium–mesenchymal interaction. This study offers new insight into the roles of extracellular proteoglycans and their distinct sulfation underlying early odontogenesis.

BackgroundThe formation of supernumerary teeth is an excellent model for studying the molecular mechanisms that control stem/progenitor cell homeostasis needed to generate a renewable source of replacement cells and tissues. Although multiple growth factors and transcriptional factors have been associated with supernumerary tooth formation, the regulatory inputs of extracellular matrix in this regenerative process remains poorly understood.ResultsIn this study, we present evidence that disrupting glycosaminoglycans (GAGs) in the dental epithelium of mice by inactivating FAM20B, a xylose kinase essential for GAG assembly, leads to supernumerary tooth formation in a pattern reminiscent of replacement teeth. The dental epithelial GAGs confine murine tooth number by restricting the homeostasis of Sox2(+) dental epithelial stem/progenitor cells in a non-autonomous manner. FAM20B-catalyzed GAGs regulate the cell fate of dental lamina by restricting FGFR2b signaling at the initial stage of tooth development to maintain a subtle balance between the renewal and differentiation of Sox2(+) cells. At the later cap stage, WNT signaling functions as a relay cue to facilitate the supernumerary tooth formation.ConclusionsThe novel mechanism we have characterized through which GAGs control the tooth number in mice may also be more broadly relevant for potentiating signaling interactions in other tissues during development and tissue homeostasis.

Dental enamel is hardest tissue in the body and is produced by dental epithelial cells residing in the tooth. Their cell fates are tightly controlled by transcriptional programs that are facilitated by fate determining transcription factors and chromatin regulators. Understanding the transcriptional program controlling dental cell fate is critical for our efforts to build and repair teeth. In this review, we describe the current understanding of these regulators essential for regeneration of dental epithelial stem cells and progeny, which are identified through transgenic mouse models. We first describe the development and morphogenesis of mouse dental epithelium in which different subpopulations of epithelia such as ameloblasts contribute to enamel formation. Then, we describe the function of critical factors in stem cells or progeny to drive enamel lineages. We also show that gene mutations of these factors are associated with dental anomalies in craniofacial diseases in humans. We also describe the function of the master regulators to govern dental lineages, in which the genetic removal of each factor switches dental cell fate to that generating hair. The distinct and related mechanisms responsible for the lineage plasticity are discussed. This knowledge will lead us to develop a potential tool for bioengineering new teeth.

Abstract Background Genetic polymorphisms have been shown to influence several physiological traits, including dental and craniofacial characteristics. Understanding the clinical relevance of genetic polymorphisms in dental practice is crucial to personalize treatment plans and improve treatment outcomes. Objective to evaluate the association between dental age and genetic polymorphisms in genes encoding estrogen receptors alpha and beta (ESR1 and ESR2, respectively) in a sample of Brazilian children. Methodology This retrospective cross-sectional study was performed with children undergoing orthodontic treatment. Patients with syndromes, congenital anomalies, craniofacial deformities, under hormonal or systemic treatment, and with a previous history of facial trauma were excluded. Panoramic radiographs were used to assess dental age according to the Demirjian, Goldstein, and Tanner method. A delta [dental age-chronological age (DA-CA)] was obtained, which shows whether the patient tends to have a normal, delayed (negative values), or advanced (positive values) dental age. DNA isolated from buccal cells was used to genotype four genetic polymorphisms: rs9340799 (A>G) and rs2234693 (C>T), located in ESR1; and rs1256049 (C>T) and rs4986938 (C>T), located in ESR2. A statistical analysis was performed and values of p0.05). Genetic polymorphisms in ESR1 and ESR2 were not associated with dental age (p>0.05). Conclusion The studied genetic polymorphisms in ESR1 and ESR2 were not associated with dental age in Brazilian children.

Background: Tooth development involves reciprocal interactions between the oral epithelium and ectomesenchyme. The inner layer cells of the enamel organ (EO), known as the inner enamel epithelium (IEE), undergo differentiation into preameloblasts and subsequently mature ameloblasts. These ameloblasts play a crucial role in the secretion of enamel matrix proteins, including amelogenin. This experimental study aimed to analyze the expression profile of amelogenin in various histological structures of human primary developing teeth, employing a relatively large sample size. Methods: This experimental study included 33 human fetuses aged between 13 and 23 weeks, with three samples obtained from each gestational age. The samples were categorized into three age groups of ≥13 and <16 gestational weeks (g.w.), <19 g.w., as well as ≥19 and ≤ 23 g.w. Hematoxylin and eosin staining, as well as immunohistochemistry staining, were performed on the samples. To assess the expression level of amelogenin in different histological structures of human primary teeth, a two-way ANOVA test was employed. The statistical significance threshold was set at P≤0.05. Results: There were statistically significant differences regarding the expression level of amelogenin in various histological structures of human primary teeth in different fetal ages (13-23 weeks), except for the maxillary central incisor and mandibular central incisor. Conclusion: Due to the profile of expression of amelogenin, it can be concluded that amelogenin expression could be associated with ameloblast and odontoblast differentiation, as well as enamel and dentin matrix deposition. In addition, the results of this study may shed light on the role of the cervical and coronal portions of the EO as stem cell reservoirs. [ABSTRACT FROM AUTHOR]

The enamel knot (EK), located at the center of cap stage tooth germs, is a transitory cluster of nondividing epithelial cells. The EK acts as a signaling center that provides positional information for tooth morphogenesis and regulates the growth of tooth cusps. To identify species-specific cuspal patterns, this study analyzed the cellular mechanisms in the EK that were related to bone morphogenetic protein (Bmp), which plays a crucial role in cell proliferation and apoptosis. To understand the cellular mechanisms in the EK, the differences between 2 species showing different cuspal patterning, mouse (pointy bunodont cusp) and gerbil (flat lophodont cusp), were analyzed with quantitative reverse transcriptase polymerase chain reaction and immunofluorescent staining. Based on these, we performed protein-soaked bead implantation on tooth germs of the 2 different EK regions and compared the cellular behavior in the EKs of the 2 species. Many genes related with cell cycle, cell apoptosis, and cell proliferation were involved in BMP signaling in the EK during tooth development. A comparison of the cell proliferation and apoptosis associated with Bmp revealed distinctive patterns of the cellular mechanisms. Our findings indicate that the cellular mechanisms, such as cell proliferation and apoptosis, in the EK are related to Bmp4 and play an important role in tooth morphogenesis. [ABSTRACT FROM AUTHOR]

The presence of supernumerary tooth (SNT) in the nasal cavity is a rare condition with limited literature data. We report two cases with a history of nasal obstruction and difficulty breathing. In both cases, clinical and radiological examination confirmed intranasal SNT. Extractions were executed in general anesthesia using Rochester-Pean instruments transnasally. In addition, a literature review of intranasal SNT was performed. The database search retrieved a total number of 50 cases in time period from 1970. to 2020. Mean age of patients was 22.5 years. Most common symptoms were unilateral obstruction of breathing and headache. Surgical extraction of intranasal SNT is recommended to eliminate the symptoms.

Tooth gemination is a dental anomaly that results from an incomplete attempt of a single tooth germ to separate during morphodifferentiation stage of odontogenesis, and it usually exhibits a large bifid crown with a single common root and root canal. This developmental anomaly more commonly affects primary dentition than the permanent, with an infrequent occurrence reported of posterior teeth. Among the posterior teeth, mandibular second premolars have reportedly shown an elevated possibility of agenesis, delayed odontogenesis, and variability of crown morphology. Both unilateral and bilateral cases of isolated macrodontia of mandibular second premolar secondary to gemination or fusion have been reported, but there is no evidence of microdontia associated with gemination in the literature till date. This case presentation reports an unusual case of isolated unilateral gemination-associated microdontia of the left mandibular second premolar in a nonsyndromic patient.

Abstract Background The preservation of biological and physiological vitality as well as the formation of dentin are among the main tasks of human dental pulp for a life time. Odontoblastic differentiation of human dental pulp stem cells (hDPSCs) exhibits the capacity of dental pulp regeneration and dentin complex rebuilding. Exploration of the mechanisms regulating differentiation and proliferation of hDPSCs may help to investigate potential clinical applications. BTB and CNC homology 1 (BACH1) is a transcription repressor engaged in the regulation of multiple cellular functions. This study aimed to investigate the effects of BACH1 on the proliferation and odontoblastic differentiation of hDPSCs in vitro. Methods hDPSCs and pulpal tissues were obtained from extracted human premolars or third molars. The distribution of BACH1 was detected by immunohistochemistry. The mRNA and protein expression of BACH1 were examined by qRT-PCR and Western blot analysis. BACH1 expression was regulated by stable lentivirus-mediated transfection. Cell proliferation and cell cycle were assessed by cell counting kit-8 assay, 5-Ethynyl-2'-deoxyuridine assay and flow cytometry. The expression of mineralization markers, alkaline phosphatase (ALP) activity and alizarin red S staining were conducted to assess the odontoblastic differentiation ability. Results BACH1 expression was stronger in the odontoblast layer than in the cell rich zone. The total and nuclear protein level of BACH1 during odontoblastic differentiation was downregulated initially and then upregulated gradually. Knockdown of BACH1 greatly inhibited cell proliferation, arrested cell cycle, upregulated the heme oxygenase-1 (HO-1) expression and attenuated ALP activity, decreased calcium deposits and downregulated the expression of mineralization markers. Treatment of Tin-protoporphyrin IX, an HO-1 inhibitor, failed to rescue the impaired odonto/osteogenic differentiation capacity. Overexpression of BACH1 increased cell proliferation, ALP activity and the expression of mineralization markers. Conclusions Our findings suggest that BACH1 is an important regulator of the proliferation and odontoblastic differentiation of hDPSCs in vitro. Manipulation of BACH1 expression may provide an opportunity to promote the regenerative capacity of hDPSCs.

Abstract Objectives The objective of this study is to confirm the developmental origin of the enamel organ and evaluate the role of E‐cadherin in tooth development by conditional deletion in the oral epithelium and its enamel organ progeny. K5‐Cre;ROSA26 compound mice were included in this study in order to confirm the oral epithelial origin of the enamel organ, as well as of the action of the K5‐Cre transgene in ablating E‐cadherin in the enamel organ. K5‐Cre;Ecadfl/fl knockout mice were included to evaluate the effects of the conditional E‐cadherin ablation onto tooth development. Material and Methods K5‐Cre transgenic mice were crossed into the ROSA26 reporter mouse to trace the cell fate of the oral epithelium and its progeny in vivo. Moreover, K5‐Cre mice were crossed into the Ecadfl/fl mice to produce K5‐Cre;Ecadfl/fl compound mouse, as well as K5‐Cre;Ecadfl/+ and Ecadfl/fl littermate controls. These litters were euthanized at postnatal day P2 to study the effects of conditional E‐cadherin ablation in vivo. Results The K5‐Cre;ROSA26 compound mouse demonstrated that the origin of the enamel organ and the structures thereof are of oral epithelial origin. Furthermore, using the K5‐Cre;Ecadfl/fl compound mouse, we determined that conditional ablation of E‐cadherin in the oral epithelium, and its progeny, results in dental anomalies involving elongation of the molar root, shrinkage of the pulp space, and alterations of the periapical area, including cementum hyperplasia. The K5‐Cre;Ecadfl/fl mice also displayed a smaller overall stature compared with heterozygotes and wild‐type littermates. Conclusions E‐cadherin is important in tooth development, including the formation of enamel, the crown, pulp space, and the roots.

Background: Epithelium-mesenchymal interactions are involved in odontogenic processes. Previous studies have focused on the intracellular signalling regulatory network in tooth development, but the functions of extracellular regulatory molecules have remained unclear. This study aims to explore the gene profile of extracellular proteoglycans and their glycosaminoglycan chains potentially involved in dental epithelium-mesenchymal interactions using high-throughput sequencing to provide new understanding of early odontogenesis. Results: Whole transcriptome profiles of the mouse dental epithelium and mesenchyme were investigated by RNA sequencing (RNA-seq). A total of 1,281 and 1,582 differentially expressed genes were identified between the dental epithelium and mesenchyme at E11.5 and E13.5, respectively. Enrichment analysis showed that extracellular regions and ECM-receptor interactions were significantly enriched at both E11.5 and E13.5. Polymerase chain reaction analysis confirmed that the extracellular proteoglycan family exhibited distinct changes during epithelium-mesenchymal interactions. Most proteoglycans showed higher transcript levels in the dental mesenchyme, whereas only a few were upregulated in the epithelium at both stages. In addition, 9 proteoglycans showed dynamic expression changes between these two tissue compartments. Gpc4, Sdc2, Spock2, Dcn and Lum were expressed at higher levels in the dental epithelium at E11.5, whereas their expression was significantly higher in the dental mesenchyme at E13.5, which coincides with the odontogenic potential shift. Moreover, the glycosaminoglycan biosynthetic enzymes Ext1, Hs3st1/5, Hs6st2/3, Ndst3 and Sulf1 also exhibited early upregulation in the epithelium but showed markedly higher expression in the mesenchyme after the odontogenic potential shift. Conclusion: This study reveals the dynamic expression profile of extracellular proteoglycans and their biosynthetic enzymes during the dental epithelium–mesenchymal interaction. This study offers new insight into the roles of extracellular proteoglycans and their distinct sulfation underlying early odontogenesis. [ABSTRACT FROM AUTHOR]

Conditions experienced in early life have long-lasting effects on offspring health. Despite this, little is known about how maternal exposure to drugs during pregnancy affects offspring teeth morphogenesis. In humans, omeprazole is a common drug used to mitigate Gastroesophageal Reflux Disease. Importantly, omeprazole is a non-specific proton-pump inhibitor, which may inhibit the proton pumps expressed in the developing tooth germ. To date, however, the effects of intrauterine life exposure to omeprazole on offspring tooth development remain unknown. In this study, we addressed this gap in a murine model. Pregnant female Swiss mice were exposed to daily doses of 40 mg/kg of omeprazole from the 5th to the 17th day of pregnancy and the effects of such exposure on offspring odontogenesis parameters such as morphological abnormalities, disruptions in the ameloblast and odontoblast layers and the presence of dentin matrix were measured. Omeprazole exposure significantly increased the prevalence (control: 21.6%; treatment: 60%; p = 0.001) and the risk (posterior mean and 95% credible interval; control: 0.230 [0.129; 0.347]; treatment: 0.593 [0.449; 0.730]) of offspring teeth morphological abnormalities, although there were no statistically significant effects of omeprazole exposure on other parameters of tooth development. These findings suggest that there are potential side-effects to offspring oral health of omeprazole use during pregnancy. [ABSTRACT FROM AUTHOR]