MicroRNA-93-5p regulates odontogenic differentiation and dentin formation via KDM6B.

BACKGROUND: Epigenetic factors influence the odontogenic differentiation of dental pulp stem cells and play indispensable roles during tooth development. Some microRNAs can epigenetically regulate other epigenetic factors like DNA methyltransferases and histone modification enzymes, functioning as epigenetic-microRNAs. In our previous study, microarray analysis suggested microRNA-93-5p (miR-93-5p) was differentially expressed during the bell stage in human tooth germ. Prediction tools indicated that miR-93-5p may target lysine-specific demethylase 6B (KDM6B). Therefore, we explored the role of miR-93-5p as an epi-miRNA in tooth development and further investigated the underlying mechanisms of miR-93-5p in regulating odontogenic differentiation and dentin formation. METHODS: The expression pattern of miR-93-5p and KDM6B of dental pulp stem cells (DPSCs) was examined during tooth development and odontogenic differentiation. Dual luciferase reporter and ChIP-qPCR assay were used to validate the target and downstream regulatory genes of miR-93-5p in human DPSCs (hDPSCs). Histological analyses and qPCR assays were conducted for investigating the effects of miR-93-5p mimic and inhibitor on odontogenic differentiation of hDPSCs. A pulpotomy rat model was further established, microCT and histological analyses were performed to explore the effects of KDM6B-overexpression and miR-93-5p inhibition on the formation of tertiary dentin. RESULTS: The expression level of miR-93-5p decreased as odontoblast differentiated, in parallel with elevated expression of histone demethylase KDM6B. In hDPSCs, miR-93-5p overexpression inhibited the odontogenic differentiation and vice versa. MiR-93-5p targeted 3' untranslated region (UTR) of KDM6B, thereby inhibiting its protein translation. Furthermore, KDM6B bound the promoter region of BMP2 to demethylate H3K27me3 marks and thus upregulated BMP2 transcription. In the rat pulpotomy model, KDM6B-overexpression or miR-93-5p inhibition suppressed H3K27me3 level in DPSCs and consequently promoted the formation of tertiary dentin. CONCLUSIONS: MiR-93-5p targets epigenetic regulator KDM6B and regulates H3K27me3 marks on BMP2 promoters, thus modulating the odontogenic differentiation of DPSCs and dentin formation.

Histone-modifying enzymes: Roles in odontogenesis and beyond.

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.

Global bibliometric mapping of dental development research for the period 2012-2021.

BACKGROUND: Dental development is a complex long-term biological process, significant attention should be paid to the dental development and health of this critical time window in childhood for the oral health of the whole life cycle. AIM: This study aimed to conduct bibliometric studies on the scientific outputs of global dental development research by the CiteSpace software. DESIGN: The global scientific outputs about dental development between January 1, 2012, and December 31, 2021, retrieved from Web of Science Core Collection, CiteSpace, and Microsoft Excel were applied for this bibliometric study. RESULTS: A total of 3746 reviews and articles were obtained from the Web of Science core database for exploring the basic publication characteristics, hotspots, and frontiers of this research field. The results showed that dental development is gaining more researcher's attention over time. In terms of countries, the USA and China were the major contributors to this research area. At the institutional level, Sichuan University ranked first. Meanwhile, international cooperation across regions was quite active. The Journal of Dental Research has exerted a broad and far-reaching influence on dental development research in both publications and citations. James P Simmer, Jungwook Kim, Charles E Smith, and Jan CC Hu are among the most influential scholars in this field. Finally, the future hotspots were proposed, covering three directions: dental analysis, tooth development, and post-translational phosphorylation of histones. CONCLUSION: In the past decade, the field of dental development has developed rapidly, and the cooperation between scholars, institutions, and researchers has become increasingly close.

Appropriate timing of treatment contributes to better root development of impacted anterior teeth in children.

INTRODUCTION: This study investigated the effects of different timings of orthodontic treatment on the root development of impacted anterior teeth in children. METHODS: The cone-beam computed tomography (CBCT) data of 45 children with impacted anterior teeth were divided into unformed root (UR) group or basically formed root (BFR) group to evaluate root length (RL) and root growth length (RGL) of impacted teeth and contralateral nonimpacted teeth pretreatment and posttreatment. In addition, 22 patients with impacted dilaceration were selected to assess the effects of the crown-root angle and root development stage on RL and RGL. The Student t test, Wilcoxon test, analysis of variance, and multiple linear regression analysis were used for statistical evaluations. RESULTS: The RL of treated impacted teeth pretreatment and posttreatment was significantly shorter than contralateral nonimpacted teeth values (P <0.05). Posttreatment, the RL and RGL of impacted teeth of the UR group were significantly greater than those of the BFR group (P <0.05). The RGL of the dilacerated root in the UR group was considerably higher than in the BFR group (P <0.05). The larger crown-root angle group had a longer posttreatment RL (P <0.05). Multiple linear regression analysis revealed that the Nolla stage of impacted teeth and RL of contralateral teeth pretreatment significantly influenced the RL of impacted teeth posttreatment. CONCLUSIONS: Prompt orthodontic treatment is necessary for children with impacted anterior teeth to release the impacted state and achieve better root development. The root length of a dilacerated tooth continued to develop under treatment, but the crown-root angle partly constrained it.

LncRNA CARMN facilitates odontogenic differentiation of dental pulp cells by impairing EZH2.

OBJECTIVE: This study aimed to reveal the potential role of CARMN in odontogenic differentiation of dental pulp cells (DPCs). METHODS: Laser capture microdissection was used to detect Carmn in DPCs and odontoblasts in P0 mice. After manipulating CARMN expression in odontogenic differentiation induced hDPCs, the state of odontogenic differentiation was evaluated by ALP staining, ARS, and related marker expression in qRT-PCR and western blotting. The subcutaneous transplantation of HA/ß-TCP loaded with hDPCs was performed to verify CARMN's role in promoting odontogenic differentiation in vivo. RNAplex and RIP were employed to reveal potential mechanism of CARMN in hDPCs. RESULTS: CARMN expressed more abundantly in odontoblasts than DPCs in P0 mice. CARMN expression boosted during in vitro odontogenic differentiation of hDPCs. CARMN overexpression enhanced odontogenic differentiation of hDPCs in vitro, while inhibition impaired the process. CARMN overexpression in HA/ß-TCP composites promoted more mineralized nodule formation in vivo. CARMN knockdown led to soared EZH2, while CARMN overexpression brought about EZH2 inhibition. CARMN functioned via direct interaction with EZH2. CONCLUSIONS: The results uncovered CARMN as a modulator during the odontogenic differentiation of DPCs. CARMN promoted odontogenic differentiation of DPCs by impairing EZH2.

Epigenetics in developmental defects of enamel: A scoping review.

OBJECTIVES: The significant role of epigenetics has been revealed in normal enamel formation process and occurrence of developmental defects. This presented literature is aiming at summarizing the regulatory function of epigenetics in physiological amelogenesis process and reviewing the epigenetic mechanisms in occurrence of developmental defects of enamel (DDE), so as to provide biological foundation evidence to support early predication and clinical management of DDE. METHOD: An extensive literature review was conducted using electronic databases MEDLINE (through PubMed), Web of Science and EMBASE up to November 30, 2022. Studies about epigenetic effects on enamel tissue or cells associated with amelogenesis, including in vivo studies using human or animal models, and in vitro studies, are selected. RESULTS: A total of 22 studies were included. Epigenetic factors or effects specifically activate or silence certain genes, which may regulate related biological activities including cell proliferation, cell differentiation, enamel secretion, and mineralization during the process of amelogenesis. Once the status of epigenetic modification is altered, the quantity and quality of enamel may both be disturbed, which can finally result in DDE. CONCLUSION: Epigenetics plays a noteworthy role of regulating the amelogenesis process and DDE potentially by altering the expression levels of genes related to enamel formation, providing a new perspective of early predication and clinical management of DDE.

METTL3 enhances dentinogenesis differentiation of dental pulp stem cells via increasing GDF6 and STC1 mRNA stability.

BACKGROUND: The dentinogenesis differentiation of dental pulp stem cells (DPSCs) is controlled by the spatio-temporal expression of differentiation related genes. RNA N6-methyladenosine (m6A) methylation, one of the most abundant internal epigenetic modification in mRNA, influences various events in RNA processing, stem cell pluripotency and differentiation. Methyltransferase like 3 (METTL3), one of the essential regulators, involves in the process of dentin formation and root development, while mechanism of METTL3-mediated RNA m6A methylation in DPSC dentinogenesis differentiation is still unclear. METHODS: Immunofluorescence staining and MeRIP-seq were performed to establish m6A modification profile in dentinogenesis differentiation. Lentivirus were used to knockdown or overexpression of METTL3. The dentinogenesis differentiation was analyzed by alkaline phosphatase, alizarin red staining and real time RT-PCR. RNA stability assay was determined by actinomycin D. A direct pulp capping model was established with rat molars to reveal the role of METTL3 in tertiary dentin formation. RESULTS: Dynamic characteristics of RNA m6A methylation in dentinogenesis differentiation were demonstrated by MeRIP-seq. Methyltransferases (METTL3 and METTL14) and demethylases (FTO and ALKBH5) were gradually up-regulated during dentinogenesis process. Methyltransferase METTL3 was selected for further study. Knockdown of METTL3 impaired the DPSCs dentinogenesis differentiation, and overexpression of METTL3 promoted the differentiation. METTL3-mediated m6A regulated the mRNA stabiliy of GDF6 and STC1. Furthermore, overexpression of METTL3 promoted tertiary dentin formation in direct pulp capping model. CONCLUSION: The modification of m6A showed dynamic characteristics during DPSCs dentinogenesis differentiation. METTL3-mediated m6A regulated in dentinogenesis differentiation through affecting the mRNA stability of GDF6 and STC1. METTL3 overexpression promoted tertiary dentin formation in vitro, suggesting its promising application in vital pulp therapy (VPT).

The Role of TNF-α in the Pathogenesis of Temporomandibular Disorders.

Temporomandibular disorder (TMD) is an oral dentofacial disease that is related to multiple factors such as disordered dental occlusion, emotional stress, and immune responses. In the past decades, tumor necrosis factor-alpha (TNF-α), a pleiotropic cytokine, has provided valuable insight into the pathogenesis of TMD, particularly in settings associated with inflammation. It is thought that TNF-α participates in the pathogenesis of TMD by triggering immune responses, deteriorating bone and cartilage, and mediating pain in the temporomandibular joint (TMJ). Initially, TNF-α plays the role of "master regulator" in the complex immune network by increasing or decreasing the production of other inflammatory cytokines. Then, the effects of TNF-α on cells, particularly on chondrocytes and synovial fibroblasts, result in pathologic cartilage degradation in TMD. Additionally, multiple downstream cytokines induced by TNF-α and neuropeptides can regulate central sensitization and inflammatory pain in TMD. Previous studies have also found some therapies target TMD by reducing the production of TNF-α or blocking TNF-α-induced pathways. All this evidence highlights the numerous associations between TNF-α and TMD; however, they are currently not fully understood and further investigations are still required for specific mechanisms and treatments targeting specific pathways. Therefore, in this review, we explored general mechanisms of TNF-α, with a focus on molecules in TNF-α-mediated pathways and their potential roles in TMD treatment. In view of the high clinical prevalence rate of TMD and damage to patients' QOL, this review provides adequate evidence for studying links between inflammation and TMD in further research and investigation.

Cell cycle control, DNA damage repair, and apoptosis-related pathways control pre-ameloblasts differentiation during tooth development.

BACKGROUND: Ameloblast differentiation is the most critical stepwise process in amelogenesis, and it is controlled by precise molecular events. To better understand the mechanism controlling pre-ameloblasts (PABs) differentiation into secretory ameloblasts (SABs), a more precise identification of molecules and signaling networks will elucidate the mechanisms governing enamel formation and lay a foundation for enamel regeneration. RESULTS: We analyzed transcriptional profiles of human PABs and SABs. From a total of 28,869 analyzed transcripts, we identified 923 differentially expressed genes (DEGs) with p < 0.05 and Fold-change > 2. Among the DEGs, 647 genes showed elevated expression in PABs compared to SABs. Notably, 38 DEGs displayed greater than eight-fold changes. Comparative analysis revealed that highly expressed genes in PABs were involved in cell cycle control, DNA damage repair and apoptosis, while highly expressed genes in SABs were related to cell adhesion and extracellular matrix. Moreover, coexpression network analysis uncovered two highly conserved sub-networks contributing to differentiation, containing transcription regulators (RUNX2, ETV1 and ETV5), solute carrier family members (SLC15A1 and SLC7A11), enamel matrix protein (MMP20), and a polymodal excitatory ion channel (TRPA1). CONCLUSIONS: By combining comparative analysis and coexpression networks, this study provides novel biomarkers and research targets for ameloblast differentiation and the potential for their application in enamel regeneration.

[Adhesion of Streptococcus mutans to removable denture crowns].

OBJECTIVE: To determine adhesion of Streptococcus mutans (S. mutans) to different kinds of removable denture crowns for the purpose of minimizing influence of removable denture on oral environment. METHODS: Three kinds of removable denture crowns (single color synthetic resin teeth, alloy pin porcelain tooth and minute color synthetic resin teeth) were adsorbed S. mutans for 24 h in sterile saliva, The adhered bacteria were counted by means of sonic oscillation and bacteria coating. RESULTS: Highest level of adhesion was found on ,the single color synthetic resin teeth was adsorbed mostly, followed by alloy pin porcelain teeth. Minute color synthetic resin teeth had far less adhesion than the others (P<0.01). CONCLUSION: Minute color synthetic resin teeth have less adhesion of S. mutans, which may be associated with their lower level of surface free energy.

Comprehensive dental treatment for "meth mouth": a case report and literature review.

Methamphetamine-induced caries (MIC) is the rampant caries often found in methamphetamine (MA) users and is often called "meth mouth". It leads to devastating effects on dentition and is the major reason that brings patients to professional help. Dental management of these patients is challenging and the most important factor is cessation of MA use. Dentists must be aware of the signs and medical risks associated with this serious condition. If duly attended to, the dental team can help patients on many levels. Treatment plans can be simplified, so that each visit does not last too long. Finally, more attention should be paid topostoperative care. This case report presents a 40-year-old man with rampant caries caused by MA abuse with poor oral hygiene and smoking habits. He was advised to stop the drug abuse and the affected teeth underwent endodontic, restorative and prosthetic rehabilitation. One year later, the patient had some secondary caries but had stopped all drug abuse.

Dental caries status and oral health behavior among civilian pilots.

OBJECTIVES: This study was aimed at investigating the caries status of Chinese civilian pilots and the relationship between caries and oral health behaviors, including sugar intake, smoking, alcohol consumption, tooth brushing, and dental check-up attendance. METHODS: This cross-sectional investigation enrolled pilots from Shenzhen Airline. A questionnaire was used to collect general information and oral health behaviors. The Decayed, Missing, and Filled Teeth (DMFT) Index, International Caries Detection and Assessment System (ICDAS) II, caries prevalence, and rate of missing teeth were recorded via oral examination. Rank correlation was used to reveal the correlation between caries and oral health behavior. RESULTS: All of the pilots were men ages 21-58 yr (mean, 31.48 ± 7.20). In the caries group (CG), the frequency of tooth brushing and flossing was a little higher; more subjects had already given up smoking; more subjects had higher alcohol consumption; the sugar intake index (SII) was a little bit higher; and the last dental attendance time (LDAT) was shorter than that in the noncaries group (NCG). A total of 211 pilots (37.95%) had caries and 85 (15.29%) had missing teeth. The average DMFT was 2.19, while the mean ICDAS was 0.72. The frequency of sugary beverage consumption was negatively correlated with caries (r = -0.088), while a positive relationship was found between LDAT and caries (r = 0.094). CONCLUSIONS: Chinese civilian pilots have relatively good oral hygiene behavior and dental health. A relationship was found between sugary beverage consumption/LDAT and caries.

[Effects of vinegar on tooth bleaching and dental hard tissues in vitro].

OBJECTIVE: To determine the effects of three acidoid bleaching agents on tooth color and dental hard tissues. METHODS: Bovine tooth blocks with 5 mm x 3 mm enamel surface exposure were randomly divided into four groups: white vinegar group (group A),apple vinegar group (group B), 30% hydrogen peroxid group (group C) and deionized water (group D), each containing ninety blocks. In each group, the tooth blocks were further equally divided into three sub groups, exposing to their respective bleaching agents for 30 s, 1 min and 3 min, respectively. The experiment was performed under simulated oral environment. The changes in color,microhardness and morphological characteristics of the tooth blocks were tested by ShadeEye NCC,microhardness tester and SEM. RESULTS: Tooth blocks exposed to white vinegar had the most notable decrease in hardness, changes in color and morphological characteristics enamel surface. CONCLUSION: White vinegar, apple vinegar and hydrogen peroxidhave bleaching effects on teeth, but white vinegar may causehigher levels of damage to the hardness and surface configuration of teeth.

Salicin alleviates periodontitis via Tas2r143/gustducin signaling in fibroblasts.

Introduction: Cells expressing taste signaling elements in non-gustatory tissues have been described as solitary chemosensory cells (SCCs) or tuft cells. These "taste-like" cells play a critical role in the maintenance of tissue homeostasis. Although the expression of SCC markers and taste signaling constituents has been identified in mouse gingivae, their role in periodontal homeostasis is still unclear. Methods: Public RNA sequencing datasets were re-analyzed and further validated with RT-PCR/qRT-PCR and immunofluorescent staining to explore the expression of TAS2Rs and downstream signaling constituents in mouse gingival fibroblasts (MGFs). The specific action of salicin on MGFs via Tas2r143 was validated with RNA silence, heterologous expression of taste receptor/Gα-gustducin and calcium imaging. The anti-inflammatory effects of salicin against LPS-induced MGFs were investigated in cell cultures, and were further validated with a ligature-induced periodontitis mouse model using Ga-gustducin-null (Gnat3-/-) mice. Results: The expression of Tas2r143, Gnat3, Plcb2, and TrpM5 was detected in MGFs. Moreover, salicin could activate Tas2r143, elicited taste signaling and thus inhibited LPS-induced chemokines expression (CXCL1, CXCL2, and CXCL5) in MGFs. Consistently, salicin-treatment inhibited periodontal bone loss, inflammatory/chemotactic factors expression, and neutrophil infiltration in periodontitis mice, while these effects were abolished in Gnat3-/- mice. Discussion: Gingival fibroblasts play a critical role in the maintenance of periodontal homeostasis via "SCC-like" activity. Salicin can activate Tas2r143-mediated bitter taste signaling and thus alleviate periodontitis in mouse, indicating a promising approach to the resolution of periodontal inflammation via stimulating the "SCC-like" function of gingival fibroblasts.

Inductive ability of human developing and differentiated dental mesenchyme.

The development of cell-based therapeutic strategies to bioengineer tooth tissue is a promising approach for the treatment of lost or damaged tooth tissue. The lack of a readily available cell source for human dental epithelial cells (ECs) severely constrains the progress of tooth bioengineering. Previous studies in model organisms have demonstrated that developing dental mesenchyme can instruct nondental epithelium to differentiate into enamel-forming epithelium. In this study, we characterized the ability of fetal and adult human dental mesenchyme to promote differentiation of human embryonic stem cell (hESC)-derived ECs (ES-ECs) into ameloblast-lineage cells. ES-ECs were co-cultured either with human fetal dental mesenchymal cells (FDMCs) or with adult dental mesenchymal cells (ADMCs) in either a three-dimensional culture system, or in the renal capsules of SCID mice. When co-cultured with FDMCs in vitro, ES-ECs polarized and expressed amelogenin. Tooth organ-like structures assembled with epithelium and encased mesenchyme and developing enamel-like structures could be detected in the complexes resulting from in vitro and ex vivo co-culture of ES-ECs and FDMCs. In contrast, co-cultured ES-ECs and ADMCs formed amorphous spherical structures and occasionally formed hair. Transcription factors were significantly upregulated in FDMCs compared to ADMCs including MSX1, GLI1, LHX6, LHX8,LEF1 and TBX1. In summary, FDMCs but not ADMCs had the capacity to induce differentiation of ES-ECs into ameloblast lineage cells. Further characterization of the functional differences between these two types of dental mesenchyme could enable reprogramming of ADMCs to enhance their odontogenic inductive competence.

Tooth loss, denture use, and all-cause and cause-specific mortality in older adults: a community cohort study.

Objectives: The available evidence on the connections between tooth loss, denture use, and mortality from all causes or specific causes among older adults is inconclusive. Therefore, we aimed to investigate the association between tooth loss, denture use, and all-cause and cause-specific mortality in older adults. Methods: A cohort of 5,403 participants aged 65 and older were recruited in the 2014 Chinese Longitudinal Healthy Longevity Survey wave and followed up in the 2018 wave. Cox proportional hazard models were used to examine the association between the number of natural teeth, denture use, and all-cause and cause-specific mortality. Results: During a mean (SD) follow-up of 3.1 years (1.3), 2,126 deaths (39.3%) occurred. Individuals with 0 and 1-9 teeth had higher mortality due to all-cause, cardiovascular disease (CVD), cancer, and other causes (all p-trend <0.05) than those with 20+ teeth. At the same time, no association was found with respiratory disease mortality. Participants who used dentures had lower mortality due to all causes [hazard ratios (HR) 0.79, 95% confidence intervals (CI) 0.71-0.88], CVD (HR 0.80, 95% CI 0.64-1.00), respiratory disease (HR 0.66, 95% CI 0.48-0.92), and other causes (HR 0.77, 95% CI 0.68-0.88) than those without dentures. Joint analysis revealed that older adults with fewer natural teeth and no dentures had higher mortality. Additionally, interaction analyses showed that the effects of the number of natural teeth on all-cause mortality were more pronounced in older adults aged <80 years (p-value for interaction = 0.03). Conclusion: Having fewer natural teeth, particularly less than 10 teeth, is linked to an increased risk of mortality from all causes, including CVD, cancer, and other causes, but not respiratory disease. The use of dentures would mitigate the adverse impact of tooth loss on all-cause and some cause-specific mortality.

Corrigendum: Tooth loss, denture use, and all-cause and cause-specific mortality in older adults: a community cohort study.

[This corrects the article DOI: 10.3389/fpubh.2023.1194054.].

Different Sources of Bone Marrow Mesenchymal Stem Cells: A Comparison of Subchondral, Mandibular, and Tibia Bone-derived Mesenchymal Stem Cells.

BACKGROUND: Stem cell properties vary considerably based on the source and tissue site of mesenchymal stem cells (MSCs). The mandibular condyle is a unique kind of craniofacial bone with a special structure and a relatively high remodeling rate. MSCs here may also be unique to address specific physical needs. OBJECTIVE: The aim of this study was to compare the proliferation and multidirectional differentiation potential among MSCs derived from the tibia (TMSCs), mandibular ramus marrow (MMSCs), and condylar subchondral bone (SMSCs) of rats in vitro. METHODS: Cell proliferation and migration were assessed by CCK-8, laser confocal, and cell scratch assays. Histochemical staining and real-time PCR were used to evaluate the multidirectional differentiation potential and DNA methylation and histone deacetylation levels. RESULTS: The proliferation rate and self-renewal capacity of SMSCs were significantly higher than those of MMSCs and TMSCs. Moreover, SMSCs possessed significantly higher mineralization and osteogenic differentiation potential. Dnmt2, Dnmt3b, Hdac6, Hdac7, Hdac9, and Hdac10 may be instrumental in the osteogenesis of SMSCs. In addition, SMSCs are distinct from MMSCs and TMSCs with lower adipogenic differentiation and chondrogenic differentiation potential. The multidirectional differentiation capacities of TMSCs were exactly the opposite of those of SMSCs, and the results of MMSCs were intermediate. CONCLUSION: This research offers a new paradigm in which SMSCs could be a useful source of stem cells for further application in stem cell-based medical therapies due to their strong cell renewal and osteogenic capacity.

IGFs in Dentin Formation and Regeneration: Progress and Remaining Challenges.

Tertiary dentin results from the interplay between the host defense and dental injury or infection. Modern endodontics aiming vital pulp treatment take the tertiary dentin formation as the interim step, with the final goal of a physiological pulp-dentin like tissue regeneration. Dental pulp stem cells have been nominated for contributing to differentiating into odontoblast-like cells who are responsible for reparative dentin formation. Understanding the original dentin formation mechanism provides us a blueprint while exploring the reparative dentin formation mechanism builds bridge to bonafide pulp-dentin tissue regeneration. Among all the regulators, growth factors have long been revealed under the spotlight. The insulin-like growth factor (IGF) family has been implicated in critical events of inducing dentin formation, which is essential for pulp treatment. The expression of IGF family members including IGF1, IGF1R, IGF2, and IGF2R has been well characterized in dental papilla cells, dental pulp stem cells, and periodontal ligament cells. Recent studies indicated IGF binding to the receptors activated pathways, including MAPK pathway, and AKT pathway, orchestrated proliferation, and differentiation, and finally, contributed to dentin formation. This review summarizes the role of IGF family in dentin formation during tooth development and tertiary dentin formation during dentin-pulp repair and sheds light on key parts of research for future treatment improvements.

Artificial intelligence-aided detection of ectopic eruption of maxillary first molars based on panoramic radiographs.

OBJECTIVES: Ectopic eruption (EE) of maxillary permanent first molars (PFMs) is among the most frequent ectopic eruption, which leads to premature loss of adjacent primary second molars, impaction of premolars and a decrease in dental arch length. Apart from oral manifestations such asdelayed eruption of PFMs and discoloration of primary second molars, panoramic radiographs can reveal EE of maxillary PFMs as well. Identifying eruption anomalies in radiographs can be strongly experience-dependent, leading us to develop here an automatic model that can aid dentists in this task and allow timelier interventions. METHODS: Panoramic X-ray images from 1480 patients aged 4-9 years old were used to train an auto-screening model. Another 100 panoramic images were used to validate and test the model. RESULTS: The positive and negative predictive values of this auto-screening system were 0.86 and 0.88, respectively, with a specificity of 0.90 and a sensitivity of 0.86. Using the model to aid dentists in detecting EE on the 100 panoramic images led to higher sensitivity and specificity than when three experienced pediatric dentists detected EE manually. CONCLUSIONS: Deep learning-based automatic screening system is useful and promising in the detection EE of maxillary PFMs with relatively high specificity. However, deep learning is not completely accurate in the detection of EE. To minimize the effect of possible false negative diagnosis, regular follow-ups and re-evaluation are required if necessary. CLINICAL SIGNIFICANCE: Identification of EE through a semi-automatic screening model can improve the efficacy and accuracy of clinical diagnosis compared to human experts alone. This method may allow earlier detection and timelier intervention and management.