Tooth dentin, secreted by odontoblasts, constitutes most of the tooth structure and provides support and sensory function. However, dentin defects are common and irreparable once they exceed a critical threshold. Human dentin develops from dental papilla (DP) cells under the guidance of the dental epithelium (DE). Here, we present a human tooth development atlas from initiation to erupted stage using single-cell RNA sequencing and spatial transcriptomics, focusing on epithelial-mesenchymal interactions. This atlas reveals that DE orchestrates DP differentiation in a WNT-NOTCH sequential activation model and identifies the key signaling molecules. DLX6-AS1+ DP cells respond to dental epithelial signals and can be isolated from adult dental pulp stem cells (DPSCs). Notably, DLX6-AS1+ DPSCs successfully generate tubular dentin in an in vivo disease model of dentin defects. This research provides valuable information on human tooth development and establishes a basis for repairing regenerative dental tissue.

Objective: This review aimed to analyze the role of amino acids in the modulation of oral biofilm metabolism and their influence on enamel demineralization and dental caries development. Methodology: A structured review of experimental, in vitro, and clinical literature was performed to assess the biological effects of amino acids on cariogenic processes. Searches were conducted in major scientific databases using terms related to amino acids, dental caries, bacterial metabolism, pH regulation, and enamel demineralization. Eligible studies were examined for mechanisms involving nitrogen metabolism, alkali production, and bacterial ecological balance within the oral environment. Results: The reviewed evidence indicates that specific amino acids, including arginine, glutamine, and glycine, contribute to caries prevention by modulating biofilm metabolic activity. These compounds enhance alkali generation through arginolytic and urease pathways, resulting in increased plaque pH and reduced acidogenicity. Consequently, enamel demineralization is attenuated, and the ecological balance of the oral microbiome shifts toward a less cariogenic profile. Additionally, amino acids were shown to interfere with the dominance of acid-producing bacteria, such as Streptococcus mutans, promoting a more stable oral environment. Conclusion: Amino acids play a significant biological role in regulating oral biofilm behavior and enamel integrity. Their incorporation into preventive strategies, including oral hygiene products and dietary approaches, may offer a promising adjunct for caries control. Further clinical research is needed to establish optimal formulations and long-term effectiveness in caries management.

Tartrazine (Tz) is a chemically synthesized food dye that is being used widely as a coloring agent in different foods. Growing pieces of evidence are reporting that these food additives are genotoxic. Since colored foods are particularly attractive to children, they are the most vulnerable to the adverse effects of food additives. Thus, this study was designed to elucidate the effect of Tz on tooth development in mice models. For this study, we administered Tz at 0.75 mg/Kg, 1.5 mg/Kg, and 3.0 mg/Kg intraperitoneally into two-week-old mice for 14 consecutive days. Then, the mice were euthanized, and mandibles were separated for removing molar (M) teeth and collecting tissue samples from the jaw. We assessed expressions of Adipoq, Bsp, Nqo1, and Sirt6 genes by polymerase chain reaction (PCR) in the tissue samples and measured the size of molar 1 (M1), molar 2 (M2), and molar 3 (M3) tooth. While there was no noticeable change in length, we observed that M3 tooth became thinner in Tz treated animal. Similarly, mice body weight was decreasing dose dependently, with a significant decline at the highest dose. Additionally, Bsp and Sirt6 gene expression were enhanced in Tz administration in mice. Overall, our data indicates that Tz has a negative effect on tooth development, and further research is needed for elucidating its mechanism of action. J. Bio-Sci. 33(1): 13-20, 2025

Amelogenin, the primary protein of the enamel matrix, has long been implicated in regulating crystal nucleation, growth, and spatial organization during tooth development. This study investigates how the absence of amelogenin affects enamel structure and mineralization. Using amelogenin knockout mice, we examine its role in maintaining enamel integrity, modulating ameloblast vesicle dynamics, and facilitating calcium ion transport through specific channels to the enamel surface. The goal is to uncover the mechanistic contributions of amelogenin to enamel biomineralization and its broader implications for dental tissue engineering and pathology. Our study demonstrates that the absence of amelogenin leads to profound disruptions in enamel formation and mineral transport. In amelogenin-null mice, the typical enamel layer was absent and replaced by peg-like, tapered mineral structures. These pegs stained positively for calcium (via alizarin red) and inorganic phosphate (via von Kossa's method), indicating aberrant mineral deposition. Electron diffraction revealed that the pegs contained bundles of thin, parallel-aligned crystals with patterns consistent with calcium hydroxyapatite, confirming their mineralized nature. At the cellular level, ameloblasts in wild-type mice displayed large, bilayered vesicles (∼200 nm in diameter) at their apical poles, containing inorganic phosphate as detected by modified submicroscopic von Kossa staining. In contrast, amelogenin-deficient ameloblasts lacked both the bilayer membrane structure and phosphate labeling within these vesicles, suggesting disrupted vesicular transport and ion packaging. Further, invivo calcium labeling with Fluo-4 showed successful apical transport of calcium to the enamel surface in wild-type mice. However, in the absence of amelogenin, calcium was aberrantly retained at the basal ameloblast pole and in the stratum intermedium. This mislocalization correlated with altered expression and distribution of intracellular calcium channel proteins, as shown by immunoreactivity. Together, these findings expand the functional role of amelogenin beyond structural organization during early enamel crystal formation. They reveal a previously underappreciated role in mediating vesicle architecture, phosphate loading, and directional calcium ion transport essential for proper enamel mineralization.

This study investigated trends in oral microbiota composition (index test) that could indicate potential candidates to identify children at risk for dental caries development compared with visual/tactile examination (reference test). MEDLINE/PubMed, Web of Science, Embase, Scopus, Lilacs, SciELO, and Google Scholar databases were searched up to September 2025. Methodological quality was assessed by Newcastle-Ottawa Scale and QUADAS-2. Qualitative synthesis was performed using all included studies. Thirteen studies that assessed the oral microbiota composition through high-throughput sequencing platforms were included comprising 740 caries-free participants at the baseline. Alloprevotella spp. and Megasphaera spp. were exclusively highly abundant in children who developed caries, whereas Peptostreptococcus spp. was exclusively highly abundant in caries-free children. The diagnostic value of the oral microbiota composition showed specificity, sensitivity, accuracy, and area under the receiver operating characteristics curve ranging from 0.6 to 1.0, 0.75 to 0.90, 0.73 to 0.93, and from 0.51 to 0.94, respectively. High risk of bias was found for the index test. The available evidence does not support the use of oral microbiota composition as a screening test to identify children at risk for caries development. Studies conducted at the species level are likely to provide results with greater sensitivity and specificity, improving risk assessment and understanding of caries-associated microbiota (PROSPERO CRD42023495648).

Genetic analysis of a Chinese family with non-syndromic tooth agenesis may reveal a potential multi-locus etiology.

BackgroundIn tooth development, the Wnt/β-catenin pathway has been shown to play a crucial role in tooth germ formation and tooth differentiation. Regeneration can be considered a replay of development. Understanding and reproducing the involvement of Wnt10a—which is reported to be the causative gene for congenital multiple tooth absence and participates in tooth development with spatiotemporal specificity—in pulp regeneration is essential for realizing dental regenerative medicine. Therefore, this study was initiated based on the concept that evaluating the dynamics of Wnt10a during angiogenesis, which is thought to occur early in dental pulp regeneration, could contribute to a more detailed elucidation of the dental pulp regeneration mechanism.MethodsDeciduous dental pulp stem cells (SHED) were isolated from human deciduous teeth, and conditioned medium (CM) was collected. In addition, after the induction of vascular differentiation of SHED, the temporal gene expression of Wnt10a, VEGF-A, Tie-2, and β-catenin was analyzed by q-PCR and protein expression by Western blotting and ELISA from 0 to 48 h and 3, 7, 14, and 21 days after the induction.ResultsCanonical Wnt signaling was activated during angiogenesis in regenerated pulp-like tissue induced by ectopic root grafting, and Wnt10a had spatio-temporal specificity. Tie-2 activation occurred during the process of induction of vascular differentiation in SHED.ConclusionsDuring angiogenesis in pulp regeneration, when SHED differentiate into blood vessels, Canonical Wnt signaling and VEGF-A are activated to form microvessels, and Tie-2 expression is enhanced to increase vessel circumference. Furthermore, Wnt10a was found to be activated in its early stages and decreased in its mature stages, with spatio-temporal specificity.Because its expression is very low, Wnt10a could be a biomarker to monitor the regenerative status of pulp regeneration.Supplementary InformationThe online version contains supplementary material available at 10.1186/s41232-025-00397-y.

Dental anomalies are disruptions in the normal development of teeth, primarily caused by genetic mutations, leading to variations in the number, shape, size, eruption, and formation of hard tissues. Although these abnormalities have been observed in various mammalian groups, their incidence and implications remain underexplored. We identified one specimen of Phyllostomus discolor with a dental anomaly. Following this discovery, we made a review of dental anomalies in Chiroptera searching for specific terms related to bats and dental anomalies and then conducted a linear regression to detect the trend of publications. Here, we report a new record of hypodontia in the Pale Spear-nosed bat Phyllostomus discolor. The hypodontia was identified in a male specimen of the Pale Spear-nosed bat from the Andean region of Colombia, characterized by a missing incisor adjacent to internal incisors in the mandible, resulting in three lower incisors—one fewer than normal. Understanding the patterns, incidence, and variations of dental anomalies across mammalian clades can enhance taxonomic studies and elucidate the mechanisms driving dental trait diversification. However, we highlight a low interest in publications barely averaging 0.73 reports per year. Contrary to what was expected, and unlike other genetic, eco-devo and evolutionary approaches used to investigate mammalian teeth, we evidence a clear reduction and possible lack of interest in this topic. We urge researchers and curators to document such anomalies that allow to challenge current hypotheses about their occurrence and evolutionary implications.

Reflective practice is essential for dental educators' professional development, academic and clinical performance, decision-making and problem-solving skills. It bridges the gap between theory and practice, fostering competency development and encouraging a deeper approach to learning. Reflective practice offers educators an opportunity to reflect on how their actions impact both teaching and learning. However, without proper guidance on how to reflect effectively, reflection often becomes anecdotal and lacks meaningful insights, which can lead to reluctance in engaging with the process. FOUR STRUCTURED REFLECTIVE PRACTICE MODELS FOR THE CLINICAL EDUCATOR: Recognising the significance of reflection for dental educators' professional development and the necessity of facilitating the process, this commentary explores the importance of reflective practice and highlights the value of structured models in enhancing teaching practice. We focus on four widely used models-Gibbs' reflective cycle, Kolb's experiential learning cycle, Schön's reflection in and on action, and Rolfe's framework for reflective practice-discussing their structure, applicability, and strengths and limitations for dental educators and practitioners. Practical resources and examples are provided to help educators integrate these models into their practice, aiming to enhance both teaching and clinical skills while fostering continuous professional growth. The models offer structured frameworks that educators can use to engage in a reflective process, allowing them to critically assess both positive and negative experiences, examine their actions, and deepen their understanding of educational practice. By utilising these models, educators can refine their teaching methods and contribute to the ongoing improvement of the clinical learning environment.

The relationship between prolonged breastfeeding practices and dental caries development: a narrative review

Dental age estimation is a crucial tool in forensic science and legal investigations, used to determine a person’s age based on their teeth. Teeth develop in a predictable manner, making them reliable indicators of age, even when other biological markers are unavailable. This technique is widely applied in criminal cases, identifying victims in mass disasters, and resolving legal disputes related to age, such as immigration cases and age verification for legal purposes. Several scientific methods help in estimating dental age across different age groups. In children and adolescents, there is an evaluation of the developmental stages of permanent teeth through radiographic analysis. Another common approach is the atlas method, which provides a series of reference images showing tooth development at different ages. Demerjian stages in developing teeth to estimate age in children and adolescents. For adults, age estimation relies on regressive changes in teeth, such as root translucency and secondary dentin deposition. These methods provide forensic experts with reliable tools for age estimation, though individual variations in genetics, nutrition, and environmental factors can affect accuracy. Recent advancements in digital imaging, artificial intelligence, and machine learning are improving the precision of dental age estimation. Techniques like Cone Beam Computed Tomography (CBCT) and automated analysis of dental structures are helping forensic scientists refine their assessments. Despite some limitations, dental age estimation remains one of the most effective techniques for age determination when birth records are unavailable or disputed. This review article aims to provide a comprehensive analysis of the various methods used in dental age estimation, highlighting their applications, advantages, and limitations in forensic and legal contexts. It will also explore recent advancements in imaging techniques and artificial intelligence that are enhancing the accuracy of age estimation. By examining existing methodologies and emerging technologies, this review seeks to contribute to the continuous improvement of forensic odontology, ensuring more reliable and standardised age estimation practices for legal and investigative purposes.

Odontogenesis-associated phosphoprotein (Odaph) is essential for tooth development. However, its role in osteoblast function and bone remodeling remains unclear. Recent studies suggest that Odaph may influence bone integrity, particularly in the maxillofacial region, thereby implicating it in craniofacial skeletal disorders. The study is designed to clarify the regulatory roles of Odaph in the proliferation, differentiation, and autophagy of osteoblasts, with particular emphasis on its participation in the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) signaling pathway. The MC3T3-E1 osteoblast cell line was employed as an in vitro model, and the effects of Odaph overexpression on cell proliferation, differentiation, and migration were assessed via qPCR, Western blotting, CCK-8 assay, EdU staining, alkaline phosphatase (ALP) staining, and Alizarin Red S (ARS) staining. RNA sequencing (RNA-seq) was carried out to screen for differentially expressed genes, and subsequent Kyoto Encyclopedia of Genes and Genomes (KEGG)/GO enrichment analyses were conducted to verify the participation of the AMPK/mTOR signaling pathway. Autophagy was assessed via Western blotting, fluorescence double staining, transmission electron microscopy, and autophagy tandem lentiviral detection. For exploring the function of autophagy in osteogenic differentiation, the autophagy inhibitor 3-MA was used to treat the cells. Furthermore, a mouse model was utilized to confirm the impacts of Odaph overexpression on osteogenesis and autophagy in vivo. Overexpression of Odaph markedly enhanced the proliferation, migration, and osteogenic differentiation of MC3T3-E1 cells, which was supported by the increased expression of osteogenic markers runt-related transcription factor 2 (RUNX2), Collagen I (COL1), and ALP. RNA-seq analysis demonstrated that genes regulated by Odaph were notably enriched in the AMPK/mTOR signaling pathway. Further validation demonstrated that Odaph increased AMPK phosphorylation while suppressing mTOR activity. Odaph overexpression also enhanced the expression of autophagy-related proteins LC3B-II and BECLIN1 while reducing p62 levels, whereas 3-MA treatment markedly attenuated these pro-osteogenic effects. Consistently, animal experiments confirmed that Odaph overexpression enhanced osteogenesis in vivo, accompanied by increased AMPK activation and autophagy induction. Odaph enhances osteoblast function through autophagy induction mediated by the AMPK/mTOR axis. These results reveal a new regulatory mechanism in bone biology and indicate that Odaph could serve as a potential therapeutic target for maxillofacial bone conditions, including jaw osteopenia and periodontal bone loss.

Survival rates for children treated for malignant diseases continue to improve, yet many survivors face persistent late oral complications that affect function, aesthetics, and quality of life. Oncological therapy, especially at a young age and following head and neck radiotherapy or intensive chemotherapy, can disrupt dental and craniofacial development, resulting in dental developmental disorders, enamel defects, salivary gland dysfunction, caries susceptibility, periodontal problems, trismus, and osteoradionecrosis of the jaw. Although these effects are partially known, they are frequently underrecognized in routine practice, and many children do not receive adequate long-term dental follow-up. A key challenge highlighted in the recent literature is the absence of structured, evidence-based guidelines for monitoring and managing late oral effects. The article emphasizes the need for clearer recommendations, better communication of oncological treatment histories, and stronger integration of dental professionals within survivorship care. Developing standardized follow-up protocols will be essential to ensure timely detection, consistent management, and improved oral health outcomes for childhood cancer survivors. This article is intended as a narrative review, synthesizing available evidence from key publications to highlight clinically relevant late oral complications and gaps in current survivorship care.

ABSTRACTExperimental studies have demonstrated that nutritional changes during development can result in phenotypic changes to mammalian cheek teeth. This developmental plasticity of tooth morphology is an example of phenotypic plasticity. Because tooth development occurs through complex interactions between manifold processes, there are many potential mechanisms which can contribute to a tooth's norm of reaction. Determining the identity of those mechanisms and the relative importance of each of them is one of the main challenges to understanding phenotypic plasticity. Quantitative proteomics combined with experimental studies allow for the identification of potential molecular contributors to a plastic response through quantification of expressed gene products. Here, we present the results of a quantitative proteomics analysis of mature upper first molars in Mus musculus from a controlled feeding experiment. Pregnant and nursing mothers were fed either a low‐dietary protein (10%) treatment diet or control (20%) diet. Low‐dietary protein was not associated with reduced molar size or skull length. However, expression of tooth‐related proteins, immune system proteins, and actin‐based myosin proteins were significantly altered in our low‐dietary protein proteomics sample. The differential expression of immune proteins along with systematic reduction in actin‐based myosin protein expression are novel discoveries for tooth proteomics studies. We propose that studies that aim to elucidate specific mechanisms of molar phenotypic plasticity should prioritize investigations into the relationships between IGF regulation and tooth development and actin‐based myosin expression and tooth development.

LRP6 β-Propeller Destabilization: Novel Variant, Phenotype and Diagnostic Implications in Tooth Agenesis

To investigate the impact of living in a war zone on acceleration of skeletal maturation and development of permanent teeth. A total of 272 Israeli children and adolescents aged 9-15 years participated in this study. The Gaza group included 106 participants from the Gaza envelope area (within 7 km of the Gaza Strip border), while the central group consisted of 166 participants from central Israel. Skeletal maturation and dental development were assessed using lateral cephalometric and panoramic radiographs, respectively. Significant differences were observed in all maturation variables, including skeletal maturation as well as maturation of the upper and lower second molars (right and left) and upper canines. The Gaza envelope group exhibited more advanced and accelerated maturation than the central group (P < .0005). Positive correlations were identified among tooth maturation, chronological age, and skeletal development (0.519 < r < 0.599). Linear regression analysis revealed that the maturation of the lower left second molar accounted for 47.8% of variance in skeletal maturation. In this study, we confirm that children living under the stress of a conflict zone exhibited earlier skeletal maturation and accelerated eruption of permanent second molars and upper canines than their peers. The early eruption of second molars and canines, particularly the lower left second molar, may serve as a predictive marker for pubertal progression.

Aims: Dental number anomalies (hypodontia and hyperdontia) are among the most common developmental disorders encountered during the tooth development process in humans. It is known that specific teeth or regions are more frequently affected in different ethnic groups. The aim of this study was to determine the prevalence of congenital dental number anomalies including both missing and supernumerary teeth-excluding third molars, in children living in the province of Gaziantep University. Methods: This study examined the panoramic radiographs of 4140 children aged 8 to 15 who were admitted to the Department of Pediatric Dentistry at Gaziantep University Faculty of Dentistry. Patients with tooth extraction, cleft lip and palate, and systemic diseases were excluded from the study. The cases were investigated regarding gender, age, number, and location of missing teeth. Results: The prevalence of hypodontia was 5.58%, with a total of 414 congenitally missing teeth detected. No statistically significant differences were found across age groups or between sexes (p&gt;0.05). The most frequently missing tooth was the mandibular second premolar, followed by teeth 45, 25, 15, and 22. One or two missing teeth were the most common findings among patients. The mandible exhibited a greater number of missing teeth compared with the maxilla.Hyperdontia was observed in 1.67% of the patients, with a total of 77 supernumerary teeth identified. A statistically significant sex related difference was found (p

This study investigates health, dental development, diet, and human-environment interactions in individuals buried in the necropolises of Pontecagnano (Campania, Italy, 7th-6th century BCE), using an integrated approach merging dental histomorphometry and calculus micro-residue analysis. The sample consists of 30 permanent teeth (canines, first and second molars) from 10 individuals. Histomorphometric analysis of dental thin sections allowed the estimation of crown formation times, initial cusp formation, crown completion, and enamel extension rates. The prevalence of Accentuated Lines, marking physiological stress events, was analyzed chronologically across tooth classes. Dental calculus analysis was performed on five individuals, identifying plant micro-remains and fungal spores. Crown formation times varied by tooth class, with canines forming the longest (mean = 1,977 ± 295 days), followed by second molars (mean = 1,176 ± 179 days) and first molars (mean = 1,094 ± 154 days). Initial cusp formation values, estimated through chronological overlap between teeth, allowed for a more accurate reconstruction of crown completion timing. Accentuated Lines prevalence peaked at 12 and 44 months, likely reflecting early childhood dietary transitions and the differential recording of stress events across different crown regions. Calculus analysis identified starch granules from cereals (Triticeae) and legumes (Fabaceae), fungal spores (Saccharomyces), and plant fibers, indicating diverse dietary practices, food processing, and extra-masticatory activities. This interdisciplinary approach reinforces the validity of combining histomorphometric and micro-residue analyses to reconstruct childhood health, adult diet, and lifestyle. Our findings align with previous research while emphasizing population-specific variations. This study enhances understanding of Iron Age biocultural adaptations, offering insights into developmental and dietary behaviors in this ancient Italian community.

This study investigates the microstructural and mechanical characteristics of primary teeth affected by ROD. A total of two ROD-affected primary teeth from two different cases underwent clinical examinations. In addition to control samples of caries-free retained primary teeth, the affected samples were examined using micro-computed tomography (micro-CT), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), and nanoindentation analysis. Clinical findings revealed yellowish discoloration, rough surfaces, and root resorption on the affected teeth. Radiographs indicated hypocalcified enamel, widened pulp chambers, and delayed development of permanent teeth. Micro-CT showed affected teeth with thinner and uneven enamel, disordered dentin, and reduced mineral density. XRD analysis found reduced crystallinity. SEM and TEM analyses revealed hypoplastic and loosely packed enamel crystals, whereas dentin exhibited disorganized collagen fibrils and poorly mineralized crystals. EDS analysis showed a reduced calcium/phosphorus ratio and an increased magnesium/calcium ratio in the affected enamel. Nanoindentation tests found reduced hardness and elastic modulus in ROD-affected enamel compared with control teeth. ROD-affected primary teeth display significant microstructural abnormalities and compromised mechanical properties, underscoring the need for early intervention and long-term monitoring to prevent complications.

Traditional Chinese medicine Pudilan synergizes with smc gene to impair cell growth and exopolysaccharides synthesis of Streptococcus mutans.