S100a6 knockdown promotes the differentiation of dental epithelial cells toward the epidermal lineage instead of the odontogenic lineage.

Tooth development is a complex process involving various signaling pathways and genes. Recent findings suggest that ion channels and transporters, including the S100 family of calcium-binding proteins, may be involved in tooth formation. However, our knowledge in this regard is limited. Therefore, this study aimed to investigate the expression of S100 family members and their functions during tooth formation. Tooth germs were extracted from the embryonic and post-natal mice and the expression of S100a6 was examined. Additionally, the effects of S100a6 knockdown and calcium treatment on S100a6 expression and the proliferation of SF2 cells were examined. Microarrays and single-cell RNA-sequencing indicated that S100a6 was highly expressed in ameloblasts. Immunostaining of mouse tooth germs showed that S100a6 was expressed in ameloblasts but not in the undifferentiated dental epithelium. Additionally, S100a6 was localized to the calcification-forming side in enamel-forming ameloblasts. Moreover, siRNA-mediated S100a6 knockdown in ameloblasts reduced intracellular calcium concentration and the expression of ameloblast marker genes, indicating that S100a6 is associated with ameloblast differentiation. Furthermore, S100a6 knockdown inhibited the ERK/PI3K signaling pathway, suppressed ameloblast proliferation, and promoted the differentiation of the dental epithelium toward epidermal lineage. Conclusively, S100a6 knockdown in the dental epithelium suppresses cell proliferation via calcium and intracellular signaling and promotes differentiation of the dental epithelium toward the epidermal lineage.

Evaluation of the effect on the permanent tooth germ and the adjacent teeth by finite element impact analysis in the traumatized primary tooth.

BACKGROUND: One of the primary concerns in the paediatric emergencies is traumatic dental injuries. OBJECTIVE: This study aimed to create trauma in primary teeth and reveal its effects finite element analysis. DESIGN: Three-dimensional models were created using cone-beam computed tomography images, representing a maxillary primary central incisor. An impact force moving at a speed of 10 m/s was simulated on the labial tooth surface in two directions: buccal and incisal. RESULTS: The stress and deformation experienced in the adjacent tooth due to the primary tooth were higher than those generated in the permanent tooth. Forces applied in the incisal direction resulted in higher levels of stress and deformation in the permanent tooth germ. The difference between the stress and deformation values in primary teeth in the forces applied in the buccal and incisal directions is 21% and 75%, respectively; in the permanent tooth germ, this difference was 233% and 100%, respectively. CONCLUSIONS: Based on the findings of this study, it is crucial to thoroughly evaluate not only the affected primary tooth but also the adjacent teeth and the permanent tooth germ in traumatic dental injuries. This comprehensive examination allows for the anticipation and management of potential long-term problems.

The Essential Role of Proteoglycans and Glycosaminoglycans in Odontogenesis.

Tooth development and regeneration are regulated through a complex signaling network. Previous studies have focused on the exploration of intracellular signaling regulatory networks, but the regulatory roles of extracellular networks have only been revealed recently. Proteoglycans, which are essential components of the extracellular matrix (ECM) and pivotal signaling molecules, are extensively involved in the process of odontogenesis. Proteoglycans are composed of core proteins and covalently attached glycosaminoglycan chains (GAGs). The core proteins exhibit spatiotemporal expression patterns during odontogenesis and are pivotal for dental tissue formation and periodontium development. Knockout of core protein genes Biglycan, Decorin, Perlecan, and Fibromodulin has been shown to result in structural defects in enamel and dentin mineralization. They are also closely involved in the development and homeostasis of periodontium by regulating signaling transduction. As the functional component of proteoglycans, GAGs are negatively charged unbranched polysaccharides that consist of repeating disaccharides with various sulfation groups; they provide binding sites for cytokines and growth factors in regulating various cellular processes. In mice, GAG deficiency in dental epithelium leads to the reinitiation of tooth germ development and the formation of supernumerary incisors. Furthermore, GAGs are critical for the differentiation of dental stem cells. Inhibition of GAGs assembly hinders the differentiation of ameloblasts and odontoblasts. In summary, core proteins and GAGs are expressed distinctly and exert different functions at various stages of odontogenesis. Given their unique contributions in odontogenesis, this review summarizes the roles of proteoglycans and GAGs throughout the process of odontogenesis to provide a comprehensive understanding of tooth development.

Spatiotemporal expression profiles of c-Mpl mRNA in the tooth germ: Comparative expression dynamics of vascularization-related genes.

BACKGROUND: Vascularization is an essential event for both embryonic organ development and tissue repair in adults. During mouse tooth development, endothelial cells migrate into dental papilla during the cap stage, and form blood vessels through angiogenesis. Megakaryocytes and/or platelets, as other hematopoietic cells, express angiogenic molecules and can promote angiogenesis in adult tissues. However, it remains unknown which cells are responsible for attracting and leading blood vessels through the dental papilla during tooth development. METHODS: Here we analyzed the spatiotemporal expression of c-Mpl mRNA in developing molar teeth of fetal mice. Expression patterns were then compared with those of several markers of hematopoietic cells as well as of angiogenic elements including CD41, erythropoietin receptor, CD34, angiopoietin-1 (Ang-1), Tie-2, and vascular endothelial growth factor receptor2 (VEGFR2) through in situ hybridization or immunohistochemistry. RESULTS: Cells expressing c-Mpl mRNA was found in several parts of the developing tooth germ, including the peridental mesenchyme, dental papilla, enamel organ, and dental lamina. This expression occurred in a spatiotemporally controlled fashion. CD41-expressing cells were not detected during tooth development. The spatiotemporal expression pattern of c-Mpl mRNA in the dental papilla was similar to that of Ang-1, which preceded invasion of endothelial cells. Eventually, at the early bell stage, the c-Mpl mRNA signal was detected in morphologically differentiating odontoblasts that accumulated in the periphery of the dental papilla along the inner enamel epithelium layer of the future cusp region. CONCLUSION: During tooth development, several kinds of cells express c-Mpl mRNA in a spatiotemporally controlled fashion, including differentiating odontoblasts. We hypothesize that c-Mpl-expressing cells appearing in the forming dental papilla at the cap stage are odontoblast progenitor cells that migrate to the site of odontoblast differentiation. There they attract vascular endothelial cells into the forming dental papilla and lead cells toward the inner enamel epithelium layer through production of angiogenic molecules (e.g., Ang-1) during migration to the site of differentiation. C-Mpl may regulate apoptosis and/or proliferation of expressing cells in order to execute normal development of the tooth.

The Prevalence, Dental Complications, and Effects of Infant Oral Mutilation.

OBJECTIVE: The aim of this scoping review on infant oral mutilation (IOM) was to study the prevalence, dental complications, and immediate and long-term effects of this practice, in addition to providing a systematic overview on existing knowledge and analysis of identified knowledge gaps on IOM. METHODS: Five electronic bibliographic databases (OVID/Medline, Embase.com, Clarivate Analytics/Web of Science Core Collection, SCOPUS, and Global Index Medicus) were searched for relevant studies. Data were entered in a bespoke data-charting form. The risk of bias was assessed by 2 independent reviewers. RESULTS: A total of 478 studies were identified from the search, out of which 42 studies were included in this review. Of the 42 studies, 19 were prevalence studies published between 1969 and 2019 which were additionally assessed for the risk of bias. We found the prevalence of IOM in Uganda was 2% to 30%; Ethiopia, 12% to 86%; Sudan, 10%; Kenya, 61% to 87%; and Tanzania 0% to 24%. Based on the prevalence studies, we observed that the most common factor motivating IOM was diarrhoea. The immediate effects of IOM were found to be infection, bleeding, anaemia, pneumonia, septicaemia, osteomyelitis, meningitis, tetanus, and blood-borne diseases, with some infants dying from these effects. Missing canines, enamel hypoplasia, malformations, abnormal eruption of permanent teeth, occlusal discrepancies, midline shift, chronic periapical infections, rotations, canine transposition, or odontomas were the long-term effects found in relation to IOM. CONCLUSIONS: IOM is a practice with serious immediate and long-term consequences that is mainly performed in East Africa (or by people originated from this region) in children aged 4 to 8 months. Most frequently affected are the deciduous canines and mostly the mandibular teeth. It is important to create professional and public awareness of the procedure in low- and high-income countries. Furthermore, there is a need for more research on the prevalence of IOM in Africa and other areas of the world to determine the long-term consequences of the practice.

Mini-Implant Insertion Using a Guide Manufactured with Computer-Aided Design and Computer-Aided Manufacturing in an Adolescent Patient Suffering from Tooth Eruption Disturbance.

Due to dental diseases, anatomical restrictions, and mixed dentition, the reduction in the number of teeth and the displacement of tooth germs pose challenges in orthodontic treatment, limiting anchorage options. The presented case demonstrates an advanced treatment solution using digital CAD/CAM-technologies and medical imaging for the creation of a mini-implant template. A 12-year-old male patient experiencing delayed tooth eruption, multiple impacted germs, and maxillary constriction underwent intraoral scanning and CBCT. Utilizing coDiagnostiXTM Version 10.2 software, the acquired data were merged to determine the mini-implant placement and to design the template. The template was then manufactured through stereolithography using surgical-guide material. Mini-implants were inserted using the produced appliance, enabling safe insertion by avoiding vital structures. Surgically exposed displaced teeth were aligned using a Hyrax screw appliance anchored on the mini-implants for rapid palatal expansion (RPE) and subsequently used as fixed orthodontics to align impacted teeth. The screw was activated daily for 10 weeks, resulting in a 7 mm posterior and 5 mm anterior maxillary transversal increase. Skeletal anchorage facilitated simultaneous RPE and tooth alignment, ensuring accuracy, patient safety, and appliance stability. The presented case shows a scenario in which computer-aided navigation for mini-implant positioning can enhance precision and versatility in challenging anatomical cases.

Arl4c is involved in tooth germ development through osteoblastic/ameloblastic differentiation.

Murine tooth germ development proceeds in continuous sequential steps with reciprocal interactions between the odontogenic epithelium and the adjacent mesenchyme, and several growth factor signaling pathways and their activation are required for tooth germ development. The expression of ADP-ribosylation factor (Arf)-like 4c (Arl4c) has been shown to induce cell proliferation, and is thereby involved in epithelial morphogenesis and tumorigenesis. In contrast, the other functions of Arl4c (in addition to cellular growth) are largely unknown. Although we recently demonstrated the involvement of the upregulated expression of Arl4c in the proliferation of ameloblastomas, which have the same origin as odontogenic epithelium, its effect on tooth germ development remains unclear. In the present study, single-cell RNA sequencing (scRNA-seq) analysis revealed that the expression of Arl4c, among 17 members of the Arf-family, was specifically detected in odontogenic epithelial cells, such as those of the stratum intermedium, stellate reticulum and outer enamel epithelium, of postnatal day 1 (P1) mouse molars. scRNA-seq analysis also demonstrated the higher expression of Arl4c in non-ameloblast and inner enamel epithelium, which include immature cells, of P7 mouse incisors. In the mouse tooth germ rudiment culture, treatment with SecinH3 (an inhibitor of the ARNO/Arf6 pathway) reduced the size, width and cusp height of the tooth germ and the thickness of the eosinophilic layer, which would involve the synthesis of dentin and enamel matrix organization. In addition, loss-of-function experiments using siRNAs and shRNA revealed that the expression of Arl4c was involved in cell proliferation and osteoblastic cytodifferentiation in odontogenic epithelial cells. Finally, RNA-seq analysis with a gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis showed that osteoblastic differentiation-related gene sets and/or GO terms were downregulated in shArl4c-expressing odontogenic epithelial cells. These results suggest that the Arl4c-ARNO/Arf6 pathway axis contributes to tooth germ development through osteoblastic/ameloblastic differentiation.

Surgical removal of third molars in a young adult: review of indications and surgical techniques.

Germectomy is a surgical method most typically performed in young adults. The indications for treatment are controversial. The purpose of this review was to determine the correct indications for germectomy and to discuss the advantages and disadvantages of the procedure. We reviewed the surgical techniques (anesthetic methods, patient preparation, and flap designs) and complications. Germectomy for orthodontic purposes is a common indication for surgical removal of tooth germ among young patients. Several studies have supported removal at an earlier age to produce fewer surgical complications. Several surgical techniques have been described in the literature.

Fibulin-1 Regulates Initiation of Successional Dental Lamina.

In humans, teeth are replaced only once, and the successional dental lamina (SDL) of the permanent tooth is maintained in a quiescent state until adolescence. Recently, we showed that biomechanical stress generated by the rapid growth of the deciduous tooth inhibits SDL development via integrin ß1-RUNX2 signaling at embryonic day 60 (E60) in miniature pigs. However, the mechanism by which RUNX2 regulates SDL initiation within the SDL stem cell niche remains unclear. In the current study, we transcriptionally profiled single cells from SDL and surrounding mesenchyme at E60 and identified the landscape of cellular heterogeneity. We then identified a specific fibroblast subtype in the dental follicle mesenchyme between the deciduous tooth and the SDL of the permanent tooth (DFDP), which constitutes the inner part of the niche (deciduous tooth side). Compared with traditional dental follicle cells, the specific expression profile of DFDP was identified and found to be related to biomechanical stress. Subsequently, we found that RUNX2 could bind to the enhancer regions of Fbln1 (gene of fibulin-1), one of the marker genes for DFDP. Through gain- and loss-of-function experiments, we proved that the biomechanical stress-mediated RUNX2-fibulin-1 axis inhibits the initiation of SDL by maintaining SDL niche homeostasis.

Resorción intracoronal preeruptiva: una revisión de la literatura / Preeruptive intracoronal resorption: a review of the literature / Reabsorção intracoronária pré-eruptiva: uma revisão da literatura

RESUMEN La resorción intracoronal preeruptiva (RIPE) es un hallazgo radiográfico que consiste en la presencia de un área radiolúcida ubicada en la dentina coronal próxima a la unión amelodentinaria en el germen de una pieza dentaria; es usualmente singular y poco profunda (menor de 1/3 de la dentina cameral). La frecuencia reportada en la literatura varía entre 0,85 % y 27,3 %; no se ha encontrado asociación con el sexo; y afecta usualmente a las piezas posteriores. Su etiología no ha sido determinada, pero evidencias histológicas apuntan a que se trataría de secuelas de resorción dentinaria. Los defectos de la RIPE deben ser considerados como lesiones de caries una vez que la pieza erupcione en boca; y aunque no se han desarrollado esquemas de tratamiento o guías de práctica clínica, los tratamientos reportados dependen de la profundidad de los defectos y son frecuentemente conservadores. El objetivo de este trabajo fue revisar los estudios descriptivos y los reportes de casos publicados acerca de la RIPE para que estos defectos sean también considerados en la práctica clínica diaria.

ABSTRACT Preeruptive intracoronal resorption (PIRR) is a radiographic phenomenon characterized by the presence of a radiolucent area situated in the coronal dentin near the amelodentine junction within the tooth's germ. Typically, this radiolucent area is singular and shallow, encompassing less than one-third of the chambered dentin. The reported frequency in the literature varies between 0.85% and 27.3%. No association with gender has been identified, and it predominantly affects posterior teeth. While its precise etiology remains undetermined, histological evidence suggests that it results from a sequelae of dentin resorption. RIPE Defects as Caries Lesions: Once the tooth erupts into the oral cavity, RIPE defects should be regarded in a manner similar to caries lesions. Despite the absence of established treatment schemes or clinical practice guidelines, reported treatments are contingent upon the depth of the defects and frequently lean towards conservative approaches. The primary aim of this study was to comprehensively review descriptive studies and published case reports focusing on RIPE defects. This effort is directed towards integrating these defects into routine clinical practice considerations.

RESUMO A reabsorção intracoronária pré-eruptiva (RIPE) é um achado radiográfico que consiste na presença de uma área radiolúcida localizada na dentina coronária próxima à junção amelodentinária no germe de um dente. Geralmente, é singular e rasa, envolvendo menos de 1/3 da dentina da câmara. A frequência relatada na literatura varia entre 0,85% e 27,3%. Não foi encontrada associação significativa com o sexo, e a RIPE tende a afetar mais comumente os dentes posteriores. Sua etiologia ainda não foi totalmente determinada, mas evidências histológicas sugerem que pode ser consequência de reabsorção da dentina. Os defeitos de RIPE devem ser considerados como lesões de cárie quando o dente irrompe na cavidade bucal. Embora não tenham sido desenvolvidos esquemas de tratamento ou diretrizes de prática clínica específicas, os tratamentos relatados para RIPE são geralmente conservadores e baseiam-se na profundidade dos defeitos. Concluindo, a revisão dos estudos descritivos e dos relatos de casos de RIPE destaca a importância de considerar esses defeitos durante a prática clínica rotineira.

A Case of Pediatric Garré's Osteomyelitis Caused by Germ Infection in the Lower Impacted Wisdom Tooth.

Garré's osteomyelitis, first described by Carl Garré in 1893, is a type of chronic osteomyelitis accompanied by hyperplastic periostitis. This condition affects relatively young patients and occurs in the fibula, femur, and other long bones as chronic non-purulent sclerosing osteomyelitis. Further, reactive periosteal bone formation develops due to chronic irritation or infection. In the maxillofacial region, it often occurs in the first molar region of the mandible due to caries and other similar causes, and it is rarely associated with impacted teeth. Herein, we present a 12-year-old female patient who primarily complained of swelling on the right side of the mandible. Despite taking antibiotics prescribed at local otolaryngologist, the swelling did not completely resolve. Thus, the patient was referred to the Department of Otorhinolaryngology at our hospital, where a dental-related disease was suspected. On a computed tomography scan, radiolucent findings were observed around the germ of the impacted wisdom tooth as well as hyperostosis in the lower jaw. Thus, Garré's osteomyelitis was suspected. The patient received oral anti-inflammatory treatment by the incision prior to surgery. Thereafter, the tooth germ was enucleated and newly-formed bone, which was laterally located to the cortical bone of the mandible, was removed under the effect of general anesthesia. On computed tomography scan 9 months after the surgery, hyperostosis in the angle of the mandible disappeared. Thereafter, pain and swelling did not recur, and the patient was doing well.

Spatial distribution of CD34 protein in primordial odontogenic tumour, ameloblastic fibroma and the tooth germ.

BACKGROUND: Primordial odontogenic tumour is a benign mixed neoplasm of recent description, which has histological similarities with other odontogenic tumours such as the ameloblastic fibroma. In this article, we investigate the architecture of the sub-epithelial layer of mesenchymal cells expressing the marker CD34 in primordial odontogenic tumour. OBJECTIVE: Analyse the spatial patterns of CD34 expression in primordial odontogenic tumour and compare them with those in ameloblastic fibroma and the normal tooth germ by means of objective imaging approaches, to better characterise these lesions. METHODS: Two cases of primordial odontogenic tumour, four cases of ameloblastic fibroma and two cases of tooth germ in cap and bell stages were used for morphological, structural and immunohistochemical analyses. RESULTS: CD34 expression was found in vascular endothelium of primordial odontogenic tumour, ameloblastic fibroma and tooth germ. In addition, a characteristic sub-epithelial expression was observed only in primordial odontogenic tumour, corresponding to 84%-86% of the sample boundaries. Moreover, the zone expressing CD34 corresponded with a higher cellularity, which was absent in ameloblastic fibroma and tooth germ. CONCLUSION: Image analysis of the primordial odontogenic tumour architecture revealed characteristics absent in other odontogenic tumours and tooth germs. This study provides additional information to support the idea that this neoplasm is a distinct entity from early stage AF or developing odontoma.

Intrauterine exposure to omeprazole increases the risk of teeth morphological anomalies in the offspring of a murine model.

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.

A deep learning approach to permanent tooth germ detection on pediatric panoramic radiographs.

Purpose: The aim of this study was to assess the performance of a deep learning system for permanent tooth germ detection on pediatric panoramic radiographs. Materials and Methods: In total, 4518 anonymized panoramic radiographs of children between 5 and 13 years of age were collected. YOLOv4, a convolutional neural network (CNN)-based object detection model, was used to automatically detect permanent tooth germs. Panoramic images of children processed in LabelImg were trained and tested in the YOLOv4 algorithm. True-positive, false-positive, and false-negative rates were calculated. A confusion matrix was used to evaluate the performance of the model. Results: The YOLOv4 model, which detected permanent tooth germs on pediatric panoramic radiographs, provided an average precision value of 94.16% and an F1 value of 0.90, indicating a high level of significance. The average YOLOv4 inference time was 90 ms. Conclusion: The detection of permanent tooth germs on pediatric panoramic X-rays using a deep learning-based approach may facilitate the early diagnosis of tooth deficiency or supernumerary teeth and help dental practitioners find more accurate treatment options while saving time and effort.

Wnt signaling promotes tooth germ development through YAP1-TGF-ß signaling.

Tooth germ development involves continuous and sequential steps with reciprocal interactions between odontogenic epithelium and the adjacent mesenchyme. Several growth factors, including Wnt, are essential for tooth germ development. Molecular mechanisms underlying Wnt/ß-catenin-regulated tooth germ development are poorly understood. In tooth germ rudiments culture, we recently demonstrated that Semaphorin 3A (Sema3A), an axonal guidance factor, stimulation reversed Wnt/ß-catenin signaling-dependent decreased cell proliferation but did not completely rescue the morphological anomalies of tooth germ, suggesting that an uncharacterized signaling pathway may be essential in Wnt/ß-catenin signaling-dependent tooth germ development. Herein, an enrichment analysis using DNA microarray data, which was obtained in our previous research, revealed that Wnt/ß-catenin signaling negatively regulates YAP1 and/or TGF-ß signalings. In odontogenic epithelial cells and tooth germ rudiments, Wnt/ß-catenin signaling activation reduced YAP1 expression, thereby suppressing YAP1 and TGF-ß signalings sequentially. Additionally, YAP1 signaling induced TGF-ß2 expression to promote TGF-ß signaling in the cells. Finally, Wnt/ß-catenin signaling-dependent disorganized tooth germ development, in which YAP1 signaling was suppressed, was reversed by TGF-ß stimulation. These results suggest that Wnt/ß-catenin signaling contributes to the tooth germ development through YAP1-TGF-ß signaling.

Ep-CAM (MOC-31) expression in tooth germ and ameloblastoma

Background: Ep-CAM, a transmembrane glycoprotein expressed in most epithelium in normal conditions, hasdiverse roles in these tissues, including in cell adhesion, proliferation, differentiation, cell cycle regu-lation, migration and intracellular signaling. It is also over-expressed in most malignant neoplasia, partic-ipating in theinitiation, progression, and metastatic dissemination of the tumor. The expression and roles of this protein in oralneoplasia, particularly in odontogenic tumors, remain unestablished. The objective of this study consisted in analyzing the expression of this protein in ameloblastoma and tooth germ.Material and Methods: Ep-CAM (MOC-31) expression was evaluated by immunohistochemistry in tooth germs(TG) (n = 16) ameloblastomas (AM) (n = 60) and 2 ameloblastic carcinomas. Sections were visualized in theirtotality with an optical microscope, and positivity observed in cell membrane and cytoplasm was graded according to the following semi-quantitative scale: Neg, "essentially unstained", for negative sections or staining <5% ofcells; + for staining of 5-50% of cells; ++ for staining >50% of cells.Results: Most tooth germs expressed MOC-31 (81.3%), strong staining was observed both in the inner epitheliumof the enamel organ and in the adjacent stellate reticulum. 16.7% of the AM cases showed MOC-31 expression,the immunoexpression expression was diffuse at the cytoplasmic and membrane level. The only two cases ofameloblastic carcinoma included were strong positive to MOC-31. No correlation was observed between proteinexpression and gender, age, clinical variants, or histological subtypes.Conclusions: Overexpression was found in TG and ameloblastic carcinoma compared to AM; further studies withdifferent experimental strategies are suggested to clarify the biological significance of this finding. (AU)

HIF-2α Inhibits Ameloblast Differentiation via Hey2 in Tooth Development.

Enamel is the highly mineralized outer layer of teeth; the cells responsible for enamel formation are ameloblasts. Local hypoxia and hypoxia inducible factor (HIF) in embryonic tissues are important to promote normal organogenesis. However, hypoxic state in tooth germs and the roles of HIF in ameloblast differentiation have not been understood. The aim of this study is to clarify the role of HIF in ameloblast differentiation during tooth germ development. We found that tooth germs were under hypoxia and HIF-1α and HIF-2α were expressed in tooth germs in embryonic mice. Then, we used HIF inhibitors to evaluate the function of HIF during tooth germ development. The HIF-2α inhibitor significantly decreased the size of tooth germs in organ culture, while the HIF-1α inhibitor did not apparently affect the size of tooth germs. The HIF-2α inhibitor enhanced the expression of amelogenin, a marker of ameloblast differentiation, in the tooth germs in organ culture and rat dental epithelial SF2 cells. Moreover, we found that the HIF-2α inhibitor-stimulating amelogenin expression was regulated by hes-related family basic helix-loop-helix transcription factor with YRPW motif 2(Hey2) in SF2 cells. These findings suggest that the HIF-2α-Hey2 axis plays an important role in ameloblast differentiation during tooth germ development.

Self-drilling screws for the prevention of dental and skeletal injuries during open reduction and internal fixation of pediatric mandibular fractures.

Facial trauma in pediatric population predisposes the child to injury of both the developing skeleton and dentition. This article aims to highlight the experience of the authors through a case report, in using self-drilling screws for fixation of mandibular fractures in pediatric age group. The use of self-drilling screws minimizes the complications such as thermal and/or mechanical damage to the developing dentition and the bone. They also provide significant advantages including ease of availability and technique, superior anchorage with primary stability, and minimizing or avoiding permanent damage to the developing tooth germs in the site of fracture. The use of self-drilling screws for mandibular open reduction and internal fixation in children is an easy, reliable, and safe technique which may have significant value addition in preventing inadvertent injury to the developing tooth germs.

[Early loss of primary molar and permanent tooth germ caused by the use of devitalizer during primary molar root canal therapy: Two cases report].

Devitalization has been widely used in the root canal therapy of primary and permanent teeth in China more than ten years ago. With the development of local anesthetic drugs and injection technologies, this treatment method with high potential risks has been gradually abandoned. However, a questionnaire survey targeted all the participants at the 2018 China Pediatric Dentistry Conference showed that the devitalizer utilization proportion was still as high as 38.1% (383/1 005), even though the ratio was much lower than 75.5% (105/139) in 2003. These doctors had pay more attention to tissue burn caused by devitalizer marginal leakage or direct leakage, and know how to identify and handle with devitalizer burn. Devitalizers were usually made of arsenic trioxide, metal arsenic or paraformaldehyde, which have cytotoxicity, allergenicity, mutagenicity, carcinogenicity, and teratogenic effects on animals. Marginal leakage of devitalizers have high risks of causing soft and hard tissue necrosis. Most of the dentists have an understanding of the potential damages of arsenic containing devitalizers, so they will choose parafor maldehyde with relatively less toxicity. Paraformaldehyde has a certain self limitation, and there are few cases reported, so some dentists lack of vigilance. Paraformaldehyde can also causes tissue necrosis if leakage happens, and the treatment methods are similar to that of arsenic containing devitalizers. When handling with devitalizers burn, the necrosed soft and hard tissue, for example gingiva, alveolar bone or teeth that cannot keep, must be completely removed until fresh blood appears, then rinse with large amount of saline and seal with iodoform gauze. This paper described two cases of devitalizer burn during the root canal treatment of primary molars, both of the doctors failed to identify the devitalizer burn symptoms in the early stage, thus didn't do proper treatments immediately after burning. Resulting in the necrosis of large area of gingiva and alveolar bone, loss of primary molars and permanent tooth germs 1-2 months after devitalizer burn. This paper reported these two cases in detail in order to warn dentists the high risks of using any kind of devitalizers, help them learn how to identify and treat devitalizer burn, and remind them to stop using devitalizers as soon as possible.

An in situ hybridization study of syndecan family during the late stages of developing mouse molar tooth germ.

Expression of syndecan-1, 2, 3, and 4 mRNAs during the late stages of tooth germ formation was investigated by in situ hybridization, using [35S]-UTP-labeled cRNA probes. Syndecan-1 mRNA was mainly expressed in the stellate reticulum and stratum intermedium as well as at the cervical region of dental papilla/dental follicle during E18.5-P3.0. Expression in the dental epithelium was enhanced during the postnatal periods, which was supported by real-time RT-PCR analysis. These spatiotemporal expression patterns may suggest specific roles of syndecan-1 in tooth formation such as tooth eruption or root formation. Syndecan-3 mRNA expression became evident in odontoblasts at E18.5, but compared to collagen type I mRNA, which was strongly expressed at this stage, syndecan-3 expression in odontoblast was restricted in mature odontoblasts beneath the cusps during the postnatal periods. This result was also supported by real-time RT-PCR analysis, and indicated that syndecan-3 may be involved in the progress of dentinogenesis rather than in the initiation of it. Syndecan-4 mRNA roughly showed comparable expression patterns to those of syndecan-3. Syndecan-2 mRNA did not show significant expression during the experimental period, but real-time RT-PCR analysis suggested that syndecan-2 expression might be enhanced with hard tissue formation.