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AbstractDental trauma is considered a complication in oral health, which has attracted the attention of researchers, as its prevalence has increased in recent years. Dental trauma in primary dentition can lead to early tooth loss and impairment of permanent successor teeth, depending on the stage of development of the tooth germ. The aim of the present study was to describe a clinical case of a 4-year-old child who was referred to a pediatric dentist after dental trauma and early loss of deciduous teeth. During the anamnesis, it was observed that the upper deciduous teeth (#51 and #61) were affected by successive traumas, resulting in the early loss of the affected teeth. Nance arch device with a tube-bar system was selected to restore function and aesthetics to the child, while the eruption of the successor permanent teeth was monitored. During the follow-up period, a delay in the eruption of #21 tooth was observed, and ulectomy of the region was indicated to allow the tooth eruption and the proper alignment of the central incisors, which occurred after 5 months of the surgical procedure. Through this report it was possible to conclude that the early diagnosis and the long-term periodic control of traumatic dental lesions in the primary dentition are of fundamental importance to prevent and minimize the damages that can occur to the permanent dentition. Keywords: Tooth Avulsion. Tooth, Deciduous. Dentition, Permanent. ResumoO traumatismo dentário é considerado uma complicação à saúde bucal que vem chamando a atenção de pesquisadores, pois sua prevalência tem aumentado nos últimos anos. O trauma dentário na dentição decídua pode ocasionar a perda precoce dos dentes, e comprometimento dos dentes sucessores permanentes, dependendo do estágio de desenvolvimento do germe dentário. O objetivo do presente estudo foi descrever um caso clínico de uma criança de 4 anos de idade que foi encaminhada ao odontopediatra após traumatismo dentário e perda precoce de dente decíduo. Durante a anamnese, foi observado que os dentes decíduos incisivos superiores (#51 e #61) foram afetados por sucessivos traumas, resultando na perda precoce dos dentes afetados. O dispositivo arco de Nance com sistema do tipo tubo-barra foi selecionado para devolver função e estética à criança, enquanto a irrupção dos dentes permanentes sucessores foi acompanhada. Durante consulta de controle, um atraso na erupção do dente #21 foi observado e a ulectomia da região foi indicada para permitir a irrupção do dente e o alinhamento adequado dos incisivos centrais, que ocorreu após 5 meses do procedimento cirúrgico. Por meio do presente relato foi possível concluir que o diagnóstico precoce e o controle periódico a longo prazo das lesões dentárias traumáticas na dentição decídua são de fundamental importância para prevenir e minimizar os prejuízos que podem ocorrer à dentição permanente. Palavras-chave: Avulsão Dentária. Dente Decíduo. Dentição Permanente.

The mammalian dentition is a serially homogeneous structure that exhibits wide numerical and morphological variation among multiple different species. Patterning of the dentition is achieved through complex reiterative molecular signaling interactions that occur throughout the process of odontogenesis. The secreted signaling molecule Sonic hedgehog (Shh) plays a key role in this process, and the Shh coreceptor growth arrest-specific 1 (Gas1) is expressed in odontogenic mesenchyme and epithelium during multiple stages of tooth development. We show that mice engineered with Gas1 loss-of-function mutation have variation in number, morphology, and size of teeth within their molar dentition. Specifically, supernumerary teeth with variable morphology are present mesial to the first molar with high penetrance, while molar teeth are characterized by the presence of both additional and absent cusps, combined with reduced dimensions and exacerbated by the presence of a supernumerary tooth. We demonstrate that the supernumerary tooth in Gas1 mutant mice arises through proliferation and survival of vestigial tooth germs and that Gas1 function in cranial neural crest cells is essential for the regulation of tooth number, acting to restrict Wnt and downstream FGF signaling in odontogenic epithelium through facilitation of Shh signal transduction. Moreover, regulation of tooth number is independent of the additional Hedgehog coreceptors Cdon and Boc, which are also expressed in multiple regions of the developing tooth germ. Interestingly, further reduction of Hedgehog pathway activity in Shhtm6Amc hypomorphic mice leads to fusion of the molar field and reduced prevalence of supernumerary teeth in a Gas1 mutant background. Finally, we demonstrate defective coronal morphology and reduced coronal dimensions in the molar dentition of human subjects identified with pathogenic mutations in GAS1 and SHH/GAS1, suggesting that regulation of Hedgehog signaling through GAS1 is also essential for normal patterning of the human dentition.

Background: Tooth development during embryonic period is a complex process and requires adequate nutrients for the formation of healthy dental tissues. Kallikrein-related peptidase-4 (KLK-4) and collagen type 1 (Coll-1) are serine proteinases secreted by ameloblast during the transition and maturation stages of the amelogenesis processes, functioning to degrade the protein matrixes, so that the enamel can reach its final hardness. Pregnancy milk contains various nutrients expected to increase the KLK-4 expression of ameloblast cells in tooth development processes Purpose: This study aimed at determining the influence of pregnancy milk on the KLK-4 and collagen type 1 (Coll-1) expression of ameloblast cells in the tooth development processes.study Method The research subjects comprised of 10 pregnant female mice (Mus Musculus L.) that were divided into: control group (given sterile aquadest) and treatment group (given pregnancy milk + sterile aquadest) for 18 days followed by the  collection of the tooth germ. The specimens were then stained using Imunnohistochemistry to see the KLK-4 and Coll-1 expressions. The data were analyzed using a pathway analysis. Result: The average KLK-4 and Coll-1 expression in the treatment group were higher than those in the control group. Based the pathway analysis, there were direct correlation of Pregnancy milk with Coll-1 expression and that with KLK-4 and Coll-1 expression as well as indirect correlation of pregnancy milk with KLK-4 expression. Conclusion: Pregnancy milk influences the Kallikrein-related peptidase-4 (KLK-4) and Coll-1 expression of ameloblast cells in the tooth development of the mice’s fetusesKeywords: Coll-1 pregnancy milk, Kallikrein-related peptidase-4 (KLK-4), Tooth development

AbstractFibroblast growth factor 8 (FGF8) is known to be a potent stimulator of canonical Wnt/β-catenin activity, an essential factor for tooth development. In this study, we analyzed the effects of co-administration of FGF8 and a CHIR99021 (GSK3β inhibitor) on differentiation of dental mesenchymal cells into odontoblasts. Utilizing Cre-mediated EGFP reporter mice, dentin matrix protein 1 (Dmp1) expression was examined in mouse neonatal molar tooth germs. At birth, expression of Dmp1-EGFP was not found in mesenchymal cells but rather epithelial cells, after which Dmp1-positive cells gradually emerged in the mesenchymal area along with disappearance in the epithelial area. Primary cultured mesenchymal cells from neonatal tooth germ specimens showed loss of Dmp1-EGFP positive signals, whereas addition of Wnt3a or the CHIR99021 significantly regained Dmp1 positivity within approximately 2 weeks. Other odontoblast markers such as dentin sialophosphoprotein (Dspp) could not be clearly detected. Concurrent stimulation of primary cultured mesenchymal cells with the CHIR99021 and FGF8 resulted in significant upregulation of odonto/osteoblast proteins. Furthermore, increased expression levels of runt-related transcription factor 2 (Runx2), osterix, and osteocalcin were also observed. The present findings indicate that coordinated action of canonical Wnt/β-catenin and FGF8 signals is essential for odontoblast differentiation of tooth germs in mice.

Abstract Background Development of dental tissue is regulated by extensive cell crosstalk based on various signaling molecules, such as bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) pathways. However, an intact network of the intercellular regulation is still lacking. Result To gain an unbiased and comprehensive view of this dental cell interactome, we applied single-cell RNA-seq on immature human tooth germ of the growing third molar, discovered refined cell subtypes, and applied multiple network analysis to identify the central signaling pathways. We found that immune cells made up over 80% of all tooth germ cells, which exhibited profound regulation on dental cells via Transforming growth factor-β, Tumor necrosis factor (TNF) and Interleukin-1. During osteoblast differentiation, expression of genes related to extracellular matrix and mineralization was continuously elevated by signals from BMP and FGF family. As for the self-renewal of apical papilla stem cell, BMP-FGFR1-MSX1 pathway directly regulated the G0-to-S cell cycle transition. We also confirmed that Colony Stimulating Factor 1 secreted from pericyte and TNF Superfamily Member 11 secreted from osteoblast regulated a large proportion of genes related to osteoclast transformation from macrophage and monocyte. Conclusions We constructed the intercellular signaling networks that regulated the essential developmental process of human tooth, which served as a foundation for future dental regeneration engineering and the understanding of oral pathology.

Background: Extrusion, lateral luxation, and intrusion are among the most serious types of dental trauma. Only a few studies have specifically focused on extrusion; the present one was aimed at reporting a case of domestic traumatic dental injury to primary tooth and describing the measures taken in managing the trauma in order to avoid future consequences to the underlying permanent tooth germ. Case report: A 3.5-year-old boy reported a dental injury with extrusion and root fracture of deciduous tooth 5.1. After intraoral and radiographic evaluation, the element was repositioned and stabilized by an orthodontic flexible splint attached to the adjacent teeth. Several follow-up checkups were made and showed good healing of the tissues and physiological exfoliation of the tooth, with a healthy and unaffected corresponding central permanent incisor. Conclusion: This case report strengthens the importance of well-timed diagnosis and treatment and of regular follow-up of traumatized teeth as they may affect both dentitions with a negative impact on Oral Health-Related Quality of Life. Conservative treatment should be taken into consideration when possible, being in some cases more appropriate.

Tooth loss has been found to adversely affect not just masticatory and speech functions, but also psychological health and quality of life. Currently, teeth replacement options include dentures, bridges, and implants. However, these artificial replacement options remain inferior to biological replacements due to their reduced efficiency, the need for replacements, and the risk of immunological rejection. To this end, there has been a heightened interest in the bioengineering of teeth in recent years. While there have been reports of successfully regenerated teeth, controlling the size and shape of bioengineered teeth remains a challenge. In this study, methacrylated hyaluronic acid (MeHA) was synthesized and microstructured in a hydrogel microwell array using soft lithography. The resulting MeHA hydrogel microwell scaffold resembles the shape of a naturally developing human tooth germ. To facilitate the epithelial–mesenchymal interactions, human adult low calcium high temperature (HaCaT) cells were seeded on the surface of the hydrogels and dental pulp stem cells (DPSCs) were encapsulated inside the hydrogels. It was found that hydrogel scaffolds were able to preserve the viability of both types of cells and they appeared to favor signaling between epithelial and mesenchymal cells, which is necessary in the promotion of cell proliferation. As such, the hydrogel scaffolds offer a promising system for the bioengineering of human tooth germs in vitro.

To elucidate the mechanism underlying the failure of root formation after irradiation, we established a method of local irradiation of the molar tooth germ and demonstrated that radiation directly affected dental root development. In the current study, to locally irradiate the lower first molars of 5-day-old C57BL/6J mice, we used lead glass containing a hole as a collimator. We confirmed that our local irradiation method targeted only the tooth germ. The irradiated root was immature in terms of apical growth, and dentin formation was irregular along the outside of the root apices. Moreover, calcified tissue apically surrounded Hertwig's epithelial root sheath, which disappeared abnormally early. This method using a local irradiation experimental model will facilitate research into radiation-induced disorders of dental root formation.