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This report presents three cases of separated root tip formation following traumatic injury with or without inflammation. The first case showed continued separate apical root formation; however, development of the main root with bony ingrowth was absent. The second case showed that separated root formation continued under the 2-year inflammatory conditions, even after apexification. The third patient showed partially connected root tip formation after apexification. By summarizing previously reported similar cases, we assessed the injury type, prevalence age, treatment performed and pattern of root development. This phenomenon may be elucidated by the special features of the apical papilla (AP). Understanding the capability of AP could help with treatments, such as regenerative endodontic procedures and trauma management for immature permanent teeth., Competing Interests: The authors declare no conflict of interest., (©2024 The Author(s). Published by MRE Press.)

Hertwig's epithelial root sheath (HERS) interacts with dental apical mesenchyme and guides development of the tooth root, which is integral to the function of the whole tooth. However, the key genes in HERS essential for root development are understudied. Here, we show that Axin1, a scaffold protein that negatively regulates canonical Wnt signaling, is strongly expressed in the HERS. Axin1 ablation in the HERS of mice leads to defective root development, but in a manner independent of canonical Wnt signaling. Further studies reveal that Axin1 in the HERS negatively regulates the AKT1-mTORC1 pathway through binding to AKT1, leading to inhibition of ribosomal biogenesis and mRNA translation. Sonic hedgehog (Shh) protein, a morphogen essential for root development, is over-synthesized by upregulated mTORC1 activity upon Axin1 inactivation. Importantly, either haploinsufficiency of the mTORC1 subunit Rptor or pharmacological inhibition of Shh signaling can rescue the root defects in Axin1 mutant mice. Collectively, our data suggest that, independently of canonical Wnt signaling, Axin1 controls ribosomal biogenesis and selective mRNA translation programs via AKT1-mTORC1 signaling during tooth root development., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Background: The aim of this study was to determine the effect of root canal filling using different obturation materials combined with apicoectomy in upper central incisors under loading with 1 N and 100 N. The effect of incomplete root formation was also investigated., Methods: Based on a CBCT-scan, a model of an upper central incisor was created. The model was altered to simulate different clinical situations: root canal treatment, apicoectomy at two different lengths and with different obturation protocols, and immature root formation after trauma. In each model the tooth was loaded with 1 and 100 N, and peak Von Mises stress of bone and tooth, elastic strain of the periodontal ligament, as well as rotation and displacement of the tooth were measured., Results: Periapical surgery increases stress in dentin and the surrounding bone. Different obturation materials only produce minor differences in a coronally intact tooth., Conclusions: Interincisal angle or loading direction strongly affects all measured values and needs to be considered when planning periapical surgery or comparing finite element analysis. Immature roots show the highest stress values in this study, reaching half the yield strength of dentine., Competing Interests: Declaration of Competing Interest Authors state no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Regenerative endodontic procedures (REPs) are frequently utilized to treat immature permanent teeth with necrotic or inflamed pulps. In most instances, these treatments successfully result in the resolution of apical periodontitis and continued root maturation. However, after reviewing over 180 REP cases treated in the Endodontics Department of Stomatology Hospital at Zhejiang University School of Medicine over the past seven years, we identified an unusual root development pattern in ten cases, characterized by root tips detached from the root body. We conducted a comprehensive analysis of the patients' demographic information, dental histories, and therapeutic efficacy, and identified five potential etiological factors for this rare phenomenon, including external force, prolonged extensive periapical inflammation, iatrogenic factors, traumatic history of primary teeth, and excessive tooth mobility. In our study, we observed that therapeutic failure was more likely in patients with initially separated root tips, while those with initially normal teeth demonstrated significantly better prognoses. We hypothesize that the initial root condition may exert a considerable influence on treatment outcomes., Competing Interests: The authors declare no conflict of interest., (©2024 The Author(s). Published by MRE Press.)

Objective: Tooth growth and wear are commonly used tools for determining the age of mammals. The most speciose order of marsupials, Diprotodontia, is characterised by a pair of procumbent incisors within the lower jaw. This study examines the growth and wear of these incisors to understand their relationship with age and sex., Design: Measurements of mandibular incisor crown and root length were made for two sister species of macropodid (kangaroos and wallabies); Macropus giganteus and Macropus fuliginosus. Histological analysis examined patterns of dentine and cementum deposition within these teeth. Broader generalisability within Diprotodontia was tested using dentally reduced Tarsipes rostratus - a species disparate in body size and incisor function to the studied macropodids., Results: In the macropodid sample it is demonstrated that the hypsodont nature of these incisors makes measurements of their growth (root length) and wear (crown length) accurate indicators of age and sex. Model fitting finds that root growth proceeds according to a logarithmic function across the lifespan, while crown wear follows a pattern of exponential reduction for both macropodid species. Histological results find that secondary dentine deposition and cementum layering are further indicators of age. Incisor measurements are shown to correlate with age in the sample of T. rostratus., Conclusions: The diprotodontian incisor is a useful tool for examining chronological age and sex, both morphologically and microstructurally. This finding has implications for population ecology, palaeontology and marsupial evolution., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Stem/progenitor cells differentiate into different cell lineages during organ development and morphogenesis. Signaling pathway networks and mechanotransduction are important factors to guide the lineage commitment of stem/progenitor cells during craniofacial tissue morphogenesis. Here, we used tooth root development as a model to explore the roles of FGF signaling and mechanotransduction as well as their interaction in regulating the progenitor cell fate decision. We show that Fgfr1 is expressed in the mesenchymal progenitor cells and their progeny during tooth root development. Loss of Fgfr1 in Gli1 + progenitors leads to hyperproliferation and differentiation, which causes narrowed periodontal ligament (PDL) space with abnormal cementum/bone formation leading to ankylosis. We further show that aberrant activation of WNT signaling and mechanosensitive channel Piezo2 occurs after loss of FGF signaling in Gli1-Cre ER ;Fgfr1 fl/fl mice. Overexpression of Piezo2 leads to increased osteoblastic differentiation and decreased Piezo2 leads to downregulation of WNT signaling. Mechanistically, an FGF/PIEZO2/WNT signaling cascade plays a crucial role in modulating the fate of progenitors during root morphogenesis. Downregulation of WNT signaling rescues tooth ankylosis in Fgfr1 mutant mice. Collectively, our findings uncover the mechanism by which FGF signaling regulates the fate decisions of stem/progenitor cells, and the interactions among signaling pathways and mechanotransduction during tooth root development, providing insights for future tooth root regeneration., (© 2024. The Author(s).)

Notum is a direct target of Wnt/β-catenin signaling and plays a crucial role as a Wnt inhibitor within a negative feedback loop. In the tooth, Notum is known to be expressed in odontoblasts, and severe dentin defects and irregular tooth roots have been reported in Notum-deficient mice. However, the precise expression pattern of Notum in early tooth development, and the role of Notum in crown and root patterns remain elusive. In the present study, we identified a novel Notum expression in primary enamel knot (EK), secondary EKs, and dental papilla during tooth development. Notum-deficient mice exhibited enlarged secondary EKs, resulting in broader cusp tips, altered cusp patterns, and reduced concavity in crown outline. These alterations in crown outline led to a reduction in cervical tongue length, thereby inducing root fusion in Notum-deficient mice. Overall, these results suggest that the secondary EK size, regulated by the Wnt/Notum negative feedback loop, has a significant impact on the patterns of crown and root during tooth morphogenesis., (© 2024. The Author(s).)

Background/aims: Dental trauma resulting in tooth intrusion is a severe injury of permanent dentition, with a prevalence of 0.5%-1.9% among traumatic dental injuries. Currently, treatment guidelines for intruded permanent teeth depend on root development and the degree of intrusion. However, the categorization of tooth maturity as mature or immature simplifies a complex continuum of root development stages. This study aims to investigate the impact of various stages of root development on the success of spontaneous re-eruption (SRE) of intruded teeth., Materials and Methods: This retrospective study analysed data from 80 children (125 teeth) aged 6-12 years who experienced dental intrusion between 2018 and 2022. Root maturation was classified based on Cvek's classification, eight were categorized as stage 1, 29 as stage 2, 44 as stage 3, 25 as stage 4, and 19 as stage 5. Intruded teeth with immature roots (Cvek's class 1-4) underwent SRE, while mature teeth (Cvek's class 5) were treated with SRE, orthodontic repositioning, or surgical repositioning based on the degree of intrusion. Primary outcome measures were successful re-eruption and secondary outcomes included observed complications during follow-up., Results: Regression analysis revealed that the patient's age, degree of root maturation, and degree of intrusion significantly affected spontaneous re-eruption (p < .05). SRE was more successful in teeth with Cvek's stages 1 and 2 compared to stages 3 and 4. Complications were associated with the treatment method, degree of root immaturity, and degree of intrusion., Conclusion: The study demonstrates that as root maturation progresses, the likelihood of re-eruption decreases, and the risk of pulp necrosis and infection increases. Therefore, teeth in later stages of immaturity (Cvek stage 4) should be repositioned orthodontically or surgically without waiting for spontaneous re-eruption., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We used fluorochrome labeling to study spatiotemporal variation of dentin apposition (DAR) and extension (DER) rates during crown and root formation of mandibular first molars from wild boar and domestic pigs. DAR was reconstructed along the course of dentinal tubules in four zones of the crown and in the upper root area. In all five zones, mean DAR increased during the first 30% to 40% of apposition, reaching highest values (22-23 μm/day) in the upper-lateral crown zone. Lowest values were recorded near the dentin-pulp interface (DPI). Typically, DARs in contemporaneously formed dentin areas were higher in more cuspally compared to more cervically/apically located zones. DER was high (>200 μm/day) in early postnatal crown dentin and then decreased markedly in cervical direction, with lowest values in the cervical crown zone. After this nadir, DER sharply increased in the upper 30% to 40% of the root extension, reaching values equaling (wild boar) or even surpassing (domestic pigs) those recorded in the upper lateral crown. After this peak, DER again decreased. While DAR did not differ markedly between wild boar and domestic pigs, the DER showed marked differences, both regarding maximum values (208.1 μm/day in wild boar, 272.2 μm/day in domestic pigs) and the timing of the root growth spurt, which occurred earlier in the domestic pigs. We consider the more rapid recruitment of secretory odontoblasts in domestic pigs (reflected by higher DER) a side effect of selection for rapid body growth during pig domestication., (© 2023 The Authors. The Anatomical Record published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Fibroblast growth factor (FGF) signalling plays a crucial role in the morphogenesis of multiple tissues including teeth. While the role of the signal has been studied in tooth crown development, little is known about root development. Of several FGF ligands involved in hard tissue formation, we suggest that FGF18 regulates the development of murine tooth roots. We implanted FGF18-soaked heparin beads into the lower first molar tooth buds at postnatal day 6 (P6), followed by transplantation under the kidney capsule. After 3 weeks, FGF18 significantly facilitated root elongation and periodontal tissue formation compared to the control. In situ hybridisation showed that Fgf18 transcripts were initially localised in the dental pulp along Hertwig's epithelial root sheath at P6 and P10 and subsequently in the dental follicle cells at P14. Fgf receptors were expressed in various dental tissues during these stages. In vitro analysis using the dental pulp stem cells revealed that FGF18 inhibited cell proliferation and decreased expression levels of osteogenic markers, Runx2, Alpl and Sp7. Consistently, after 1 week of kidney capsule transplantation, FGF18 application did not induce the expression of Sp7 and Bsp, but upregulated Periostin in the apical region of dental mesenchyme in the grafted molar. These findings suggest that FGF18 facilitates molar root development by regulating the calcification of periodontal tissues., (© 2024 Anatomical Society.)

Methylation modification is one of the most common epigenetic modification regulation in eukaryotes, including histone methylation, DNA methylation, RNA methylation, etc., which plays an important regulatory role in physiological processes and pathologic occurrence and development. Tooth root development is carried out by both epithelial and mesenchymal cells and involves a variety of cell-molecular interactions. In recent years, a large number of studies have found that methylation plays a key role in the regulation of tooth root development and expands the mechanism network of tooth root development. In this paper, we review the role and mechanism of methylation modification during root development.

Objectives: To evaluate root development of pediatric patients treated with Alt-RAMEC + Face mask therapy., Material and Methods: The 19 subjects (9 girls, 10 boys; mean age: 8.6 ± 1.1 years) treated with Alt-RAMEC and a Petit-type face mask were included to the study. The cone-beam tomography (CBCT) records of these patients were used to quantify the root length. The root length measurements of 456 permanent teeth (maxillary-mandibular incisors, canines, premolars, and first molars) were performed at the beginning of the treatment (T0), after the Alt-RAMEC protocol (T1), and at the end of the face mask treatment (T2) using Planmeca Romexis software., Results: Tooth length values increased significantly in the maxillary teeth except the central incisors, left lateral incisor, the palatal root of the right first molar, and distal and palatinal roots of the left first molar (p < 0.05). Mandibular teeth also showed significant increase in the root length except mandibular central incisors and the distal root of left first molar (p < 0.05). The change in tooth lengths from T0 to T1 showed positive delta values. The comparison of the change in tooth lengths after the Alt-RAMEC protocol and after the face mask therapy showed that ∆T2-T1 was statistically significantly higher compared with ∆T1-T0 (p < 0.05)., Conclusions: Alt-RAMEC + Face mask therapy seem not to inhibit root development of maxillary and mandibular teeth in the mixed dentition., Clinical Relevance: These findings suggest that early Alt-RAMEC + Face mask interventions have not played a negative role in root development. However, further studies involving a control group need to be performed., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: In this study, we attempted to define the precise window of time for molar root elongation using a gain-of-function mutation of β-catenin model., Materials and Methods: Both the control and constitutively activated β-catenin (CA-β-cat) mice received a one-time tamoxifen administration (for activation of β-catenin at newborn, postnatal day 3, or 5, or 7, or 9) and were harvested at the same stage of P21. Multiple approaches were used to define the window of time of postnatal tooth root formation., Results: In the early activation groups (tamoxifen induction at newborn, or P3 or P5), there was a lack of molar root elongation in the CA-β-cat mice. When induced at P7, the root length was slightly reduced at P21. However, the root length was essentially the same as that in the control when β-cat activated at P9. This study indicates that root elongation occurs in a narrow time of window, which is highly sensitive to a change of β-catenin levels. Molecular studies showed a drastic decrease in the levels of nuclear factor I-C (NFIC) and osterix (OSX), plus sharp reductions of odontoblast differentiation markers, including Nestin, dentin sialoprotein (DSP), and dentin matrix protein 1 (DMP1) at both mRNA and protein levels., Conclusions: Murine molar root elongation is precisely regulated by the Wnt/β-catenin signaling within a narrow window of time (newborn to day 5)., (© 2020 Wiley Periodicals LLC.)

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., (©2021 by Radiation Research Society. All rights of reproduction in any form reserved.)

β-catenin, a key mediator of Wnt signaling, plays multiple roles in tooth development. However, the role of β-catenin in Hertwig's epithelial root sheath (HERS) during root formation remains unclear. In this study, we generated inducible tissue-specific β-catenin conditional knockout mice (Ctnnb1 i∆shh ) to investigate how β-catenin in HERS affects tooth root development. The inactivation of β-catenin in HERS led to interrupted root elongation due to premature disruption of HERS. This phenotype was accompanied by reduced cell-cell adhesion and decreased expression of junctional proteins, as well as increased epithelial-to-mesenchymal transition of HERS cells upon β-catenin depletion. Accordingly, stabilization of β-catenin in HERS (Catnb i∆shh ) led to the formation of unfragmented HERS and resulted in the failure of HERS dissociation, with increased expression of junctional proteins. Our results suggest that fine control of β-catenin is important for HERS to guide root formation through regulating its structural integrity., (© 2020 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.)

We cryopreserved mouse tooth germs with widely open cervical margins of the enamel organ to overcome difficulties in cryoprotectant permeation and tested their efficacy by transplanting them into recipient mice. The upper right first molar germs of 8-day-old donor mice were extracted and categorized into the following four groups according to cryopreservation time: no cryopreservation, 1 week, 1 month, and 3 months. The donor tooth germs were transplanted into the upper right first molar germ sockets of the 8-day-old recipient mice. The upper left first molars of the recipient mice were used as controls. The outcome of the transplantation was assessed at 1, 2, and 3 weeks after transplantation. Stereomicroscopic evaluation revealed that most of the transplanted teeth erupted by 3 weeks after transplantation. Micro-computed tomography analysis revealed root elongation in the transplanted groups as well as in the controls. There was no significant difference between the cryopreserved and non-cryopreserved transplanted teeth, but the roots of the cryopreserved teeth were significantly shorter than those of the control teeth. Histological examination revealed root and periodontal ligament formations in all the transplanted groups. These results suggest that the transplantation of cryopreserved tooth germs facilitates subsequent root elongation and tooth eruption.

Chromatin remodelers often show broad expression patterns in multiple cell types yet can elicit cell-specific effects in development and diseases. Arid1a binds DNA and regulates gene expression during tissue development and homeostasis. However, it is unclear how Arid1a achieves its functional specificity in regulating progenitor cells. Using the tooth root as a model, we show that loss of Arid1a impairs the differentiation-associated cell cycle arrest of tooth root progenitors through Hedgehog (Hh) signaling regulation, leading to shortened roots. Our data suggest that Plagl1, as a co-factor, endows Arid1a with its cell-type/spatial functional specificity. Furthermore, we show that loss of Arid1a leads to increased expression of Arid1b, which is also indispensable for odontoblast differentiation but is not involved in regulation of Hh signaling. This study expands our knowledge of the intricate interactions among chromatin remodelers, transcription factors, and signaling molecules during progenitor cell fate determination and lineage commitment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mammalian tooth crown formation has long served as a model for investigating how patterning and morphogenesis are orchestrated during development. However, the mechanism underlying root patterning and morphogenesis remains poorly understood. In this study, we find that Lhx6 labels a subpopulation of root progenitor cells in the apical dental mesenchyme, which is closely associated with furcation development. Loss of Lhx6 leads to furcation and root number defects, indicating that Lhx6 is a key root patterning regulator. Among the multiple cellular events regulated by Lhx6 is the odontoblast fate commitment of progenitor cells, which it controls in a cell-autonomous manner. Specifically, Lhx6 loss leads to elevated expression of the Wnt antagonist Sfrp2 and down-regulation of Wnt signaling in the furcation region, while overactivation of Wnt signaling in Lhx6+ progenitor cells partially restore the furcation defects in Lhx6-/- mice. Collectively, our findings have important implications for understanding organ morphogenesis and future strategies for tooth root regeneration., Competing Interests: The authors have declared that no competing interests exist.

Tooth root development occurs through the interaction of multiple growth factors and transcription factors expressed in Hertwig's epithelial root sheath (HERS) and dental mesenchyme. Previously, we demonstrated that bobby sox homolog (Bbx) regulates odontoblast differentiation of human dental pulp stem cells. Here, we generated Bbx knockout (Bbx -/- ) mice to address the functional role of Bbx in tooth formation. During tooth development, Bbx was expressed in both dental epithelium and mesenchyme. However, molar and incisor morphology in Bbx -/- mice at postnatal Day 0 (P0) exhibited no prominent abnormalities compared with their wild-type (Bbx +/+ ) littermates. Until P28, the crown morphology in Bbx -/- mice was not distinctively different from Bbx +/+ littermates. Meanwhile, the length of the mandibular base in Bbx -/- mice was notably less at P28. Compared with Bbx +/+ mice, the mesial and distal root lengths of the first molar were reduced by 21.33% and 16.28% at P14 and 16.28% and 16.24% at P28, respectively, in Bbx -/- mice. The second molar of Bbx -/- mice also showed 10.16% and 6.4% reductions at P28 in the mesial and distal lengths, compared with Bbx +/+ mice, respectively. The gene expression analysis during early tooth root formation (P13) showed that the expression of dentin sialophosphoprotein (Dspp) was significantly decreased in Bbx -/- mice. Collectively, our data suggest that Bbx participates in tooth root formation and might be associated with the regulation of Dspp expression., (© 2020 Wiley Periodicals LLC.)

Progenitor cells are crucial in controlling organ morphogenesis. Tooth development is a well-established model for investigating the molecular and cellular mechanisms that regulate organogenesis. Despite advances in our understanding of how tooth crown formation is regulated, we have limited understanding of tooth root development. Runt-related transcription factor 2 (RUNX2) is a well-known transcription factor in osteogenic differentiation and early tooth development. However, the function of RUNX2 during tooth root formation remains unknown. We revealed in this study that RUNX2 is expressed in a subpopulation of GLI1+ root progenitor cells, and that loss of Runx2 in these GLI1+ progenitor cells and their progeny results in root developmental defects. Our results provide in vivo evidence that Runx2 plays a crucial role in tooth root development and in regulating the differentiation of root progenitor cells. Furthermore, we identified that Gli1, Pcp4, NOTUM, and Sfrp2 are downstream targets of Runx2 by integrating bulk and single-cell RNA sequencing analyses. Specifically, ablation of Runx2 results in downregulation of WNT inhibitor NOTUM and upregulation of canonical WNT signaling in the odontoblastic site, which disturbs normal odontoblastic differentiation. Significantly, exogenous NOTUM partially rescues the impaired root development in Runx2 mutant molars. Collectively, our studies elucidate how Runx2 achieves functional specificity in regulating the development of diverse organs and yields new insights into the network that regulates tooth root development. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

The age threshold of 14 years has become vital in proving legal violations involving children, particularly in cases of suspected child labour, child pornography and the minimum age of criminal responsibility. In recent years, there has been great interest in the evaluation of age in children and sub-adults using analysis of regressive changes in teeth, with a particular focus on age thresholds that are of medico-legal importance. This research aimed to compare the sensitivity and specificity of stages of root pulp visibility by Olze et al. in a sample of South Indian children aged between 12 and 16 years, with an age threshold of 14 years, using receiver operating characteristic curves and the area under the curve (AUC). Among the four stages of root pulp visibility, stage 2 showed the highest AUC in both female and male cohorts. For stage 2, lower sensitivity and higher specificity values were recorded, indicating the possibility of type II errors (i.e. false negatives). In both sexes, stage 2 had a higher AUC (i.e. 0.696 in females and 0.706 in males, respectively). Based on our findings, it can be concluded that this staging method in lower first molars is of limited value in indicating the legal age threshold of 14 years. Future research should validate the proposed approach in a larger sample and consider how to improve predictions in this area.

Forensic odontologists often confront with conceptually simple medicolegal question of whether an individual is a juvenile or an adult. The demand for additional research into extending dental age estimation methods in late adolescence is never the less, especially in those who have passed 15 years and are suspected older than 18 years. The present research investigated the regressive dental characteristic, i.e. radiographic visibility of the root pulp in mandibular second molars for the purpose of age assessment, especially for determining the age over 18 years. Nine hundred thirty-six orthopantomograms comprised of 436 males and 500 females aged from 14 to 22 years were examined. Descriptive statistics were performed for each stage in both sexes. The correlation statistics revealed that there is a strong, positive correlation between the chronological age and root pulp visibility stages. The analysis revealed that stage 0 occurred first at the age of 14 years in both sexes. Stage 1 first occurred at the age of 14.26 years in females and 14.74 years in males. Stage 2 was first achieved at the age of 18.6 and 15.2 years in males and females, respectively. The suitability of the studied characteristics in mandibular second molars for age estimation could be confirmed but of limited value. The presence of this stage 2 root pulp visibility in male subjects represents a potential criterion for indicating the age over 18 years. In future studies, the pattern of secondary dentin formation in other tooth types should be investigated.

Hertwig's epithelial root sheath (HERS) plays indispensable roles in tooth root development, including controlling the shape and number of roots, dentin formation, and helping generate the cementum. Based on these characteristics, HERS cell is a potential seed cell type for tooth-related tissue regeneration. However, the application is severely limited by a lack of appropriate culture methods and small cell numbers. Methods: Here, we constructed a 3D culture method to expand functional HERS cells into spheroids, and investigated characteristics and application of dental tissue regeneration of these spheroids. HERS spheroids and HERS cells (2D monolayer culture) were compared in terms of biological characteristics (such as proliferation, self-renewal capacity, and stemness) in vitro and functions (including differentiation potential and inductive ability of dentin formation) both in vitro and in vivo . Further, transcriptome analysis was utilized to reveal the molecular mechanisms of their obvious differences. Results: HERS spheroids showed obvious superiority in biological characteristics and functions compared to 2D monolayers of HERS cells in vitro . In vivo , HERS spheroids generated more mineralized tissue; when combined with dental papilla cells (DPCs), HERS spheroids contributed to dentin-like tissue formation. Moreover, the generation and expansion of HERS spheroids rely to some degree on the HIF-1 pathway. Conclusion: HERS spheroid generation is beneficial for functional HERS cell expansion and can provide a useful cell source for further tooth regeneration and mechanistic research. Notably, HIF-1 pathway plays a critical role in HERS spheroid formation and function., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The purpose of the present study was to assess the early stages of development of mouse first molar roots in the osteopetrotic context of RANKL invalidation in order to demonstrate that the radicular phenotype observed resulted not only from defective osteoclasts, but also from loss of cell-to-cell communication among dental, periodontium and alveolar bone cells involving RANKL signaling. Two experimental models were used in this study: Rankl mutants with permanent RANKL invalidation, and C57BL/6J mice injected during the first postnatal week with a RANKL neutralizing antibody corresponding to a transient RANKL invalidation. The dento-alveolar complex was systematically analyzed using micro-CT, and histological and immunohistochemical approaches. These experiments showed that the root elongation alterations observed in the Rankl -/- mice were associated with reduced proliferation of the RANK-expressing HERS cells with a significant decrease in proliferating cell nuclear antigen (PCNA) expression and a significant increase in P21 expression. The phenotypic comparison of the adult first molar root at 35 days between permanent and transitory invalidations of RANKL made it possible to demonstrate that alterations in dental root development have at least two origins, one intrinsic and linked to proliferation/differentiation perturbations in dental-root-forming cells, the other extrinsic and corresponding to disturbances of bone cell differentiation/function.

Sonic hedgehog (Shh) is a secreted protein with important roles in mammalian embryogenesis. During tooth development, Shh is primarily expressed in the dental epithelium, from initiation to the root formation stages. A number of studies have analyzed the function of Shh signaling at different stages of tooth development and have revealed that Shh signaling regulates the formation of various tooth components, including enamel, dentin, cementum, and other soft tissues. In addition, dental mesenchymal cells positive for Gli1, a downstream transcription factor of Shh signaling, have been found to have stem cell properties, including multipotency and the ability to self-renew. Indeed, Gli1-positive cells in mature teeth appear to contribute to the regeneration of dental pulp and periodontal tissues. In this review, we provide an overview of recent advances related to the role of Shh signaling in tooth development, as well as the contribution of this pathway to tooth homeostasis and regeneration., Competing Interests: The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

Introduction: The determination of age of majority (the 18-year-old threshold) using the popular Demirjian tooth staging method is unreliable, so other maturity markers are required. This study examines whether the Root Pulp Visibility (RPV) of the mandibular third molar is a useful indicator of age., Methods: One thousand six dental panoramic radiographs (DPTs) were examined and the left mandibular third molar assessed according to the RPV stages using the method of Olze et al. (Int J Legal Med 124:183-186, 2010) as modified by Lucas et al. (Forensic Sci Int 270:98-102, 2017). Six hundred sixty-two DPTs, 288 males and 374 females, satisfied the inclusion criteria., Results: Individuals who had reached stages RPV-A and RPV-B were represented in a wide range of ages spanning the 18-year-old threshold. Individuals who had reached stages RPV-C and RPV-D were all above the 18-year-old threshold. It was not possible to analyse a large number of DPTs for various reasons., Discussion: Individuals whose mandibular third molar exhibited stages RPV-C and RPV-D may be deemed to have reached the age of majority. These results are consistent with other published studies. Variation in the rate of development of the third molar limits the applicability of this method., Conclusions: RPV staging is an accurate method of determining the 18-year-old threshold. Substitute methods are required in a large number of cases.

Age estimation has a great importance due to legal requirements. The aim of our study was to determine the applicability of two different methods in age estimation; one of them based on the calculation of the visibility of the root pulp of mandibular third molar teeth and the other based on the calculation of the tooth coronal index (TCI) in the mandibular first and second molar teeth in the 9059 digital orthopantomogram of people aged between 15 and 40 in Bursa. In the first method in which the visibility of the fully mineralized root pulp of the mandibular third molar teeth was evaluated in 4 stages; the stages 0, 1, 2, and 3 were observed regardless of sex at the earliest 17.2; 19.1; 20.1, and 25.1 years, respectively. In the second method in which TCI was regressed on chronological age using measuring crown and coronal pulp cavity heights, the most accurate age estimation model based on simple linear regression for all cases without any sex difference was found to be with right first molar tooth (SEE ±7304 years) and the most accurate age model based on multiple regression model was found to be with bilateral first molar teeth (SEE ±7413 years). In conclusion, we believe that the root pulp visibility of the third molar teeth can be applied safely for stages 1, 2, and 3 at 16, 17, and 21 years of ages, respectively. A correlation was also found between TCI and age, and our findings have shown that both methods are available for forensic purposes.

The main criterion of dental age assessment in living adolescents and young adults is the evaluation of third molars' mineralization. Concerning forensic age assessment after the completion of third molars' mineralization, apposition of secondary dentine and narrowing of the periodontal membrane as seen as decreasing radiolucent areas in the radiographs for mandibular third molars have already been described as regressive features. The present study examines the combination of both these features for the purpose of age assessment in regression analyses after rescaling the data to make it on the interval scale. To this end, a total of 1245 orthopantomograms was evaluated, taken from 606 females and 639 males in the age group of 15-40 years. The apposition of secondary dentine and narrowing of the periodontal membrane as seen as decreasing radiolucent areas in the radiographs were determined for the lower third molars. The correlation of the features with the chronological age was assessed by means of rescaled regression analyses. Furthermore, regression formulas for age assessment were established. The values of the standard error of estimate ranged between 3.55 and 4.52 years. In general, the rescaled regression of the examined features appears to be suited for forensic age assessment. A limitation of the present study is the comparatively low number of evaluable teeth in the examined age group. Due to an incomplete development or a lack of the mandibular third molars, only a mere half of the respective teeth could be included in the statistical analysis.

From a legal and penalty point of view, it is essential to conclude if an individual has reached the legal age (also known as age of majority). Although Cameriere's third molar maturity index (I 3M ) has been used to discriminate between adults and minors, no study has tested the applicability of I 3M in the Eastern Chinese population. The aim of this study was to assess the validity of the region-specific cut-off value of I 3M for discriminating minors from adults in an Eastern Chinese population. Five hundred fifty-six subjects (276 males and 280 females) aged 14-24 years participated in this study. A logistic regression analysis was conducted by considering the adult and minor ages as dichotomous dependent variables and I 3M and sex as predictor variables. The results showed that sex was not statistically significant in distinguishing adults and minors. The receiver operating curve analysis showed the best performance of the cut-off value of I 3M  < 0.08 in discriminating adults from minors. Furthermore, the diagnostic test showed the proportion of accuracy was 90.22% in males and 86.43% in females. The sensitivity and specificity for males were 88% and 94.06%, respectively, while those for females were 83.71% and 91.18%, respectively. The estimated Bayes post-test probability was 97.18% and 96.01% in males and females respectively. Therefore, I 3M  < 0.08 may be a useful tool for indicating the legal age in Eastern Chinese population., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Recent studies of dental development have indicated that root growth rates are linked to the eruption of some permanent tooth types in modern humans and Pan troglodytes. Little is known about the potential links between these aspects of dental development in deciduous teeth of any primate species. This histology study calculates the rate at which roots extend in length for human deciduous maxillary teeth and a small sample of deciduous canines and premolars from P. troglodytes and Pongo pygmaeus. Links are sought between root extension rates and previously published data for deciduous tooth emergence in each of these species. Results reported here provide the first evidence that the roots of human deciduous incisors, canines, and premolars extend in length at an accelerated rate as these teeth emerge. Accelerated extension rates in a deciduous canine from Pan coincided with the age that this tooth type emerged in captive chimpanzees. High extension rates in a canine from Pongo preceded emergence age. Preliminary observations indicate that deciduous canine and premolar roots of Pan and Pongo extend in length rapidly when compared to these tooth types from modern human children. This study provides a starting point from which to investigate new links between the incremental development of deciduous roots and tooth emergence in primates., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Recent observations performed in the orthodontic department of La Pitié-Salpêtrière hospital in Paris reported an increase of non-familial eruption defects of permanent molars. Our recent data have evidenced the involvement of osteoclasts (OC) in both the eruption and the dental retention processes through the RANKL/RANK/OPG signaling pathway. These facts are at the origin of the hypothesis of the existence of an environmental etiology for those eruption defects that would correspond to the perturbation of cellular autocrine/paracrine signaling pathways as the RANKL/ RANK/OPG., Materials and Methods: C57BL/6 mice were submitted to repeated injections with anti-RANKL neutralizing antibody during the nine days following birth. A phenotypic comparison with transgenic mice overexpressing RANK was performed for the functional characterization of the RANKL/RANK/OPG pathway. The dento-alveolar complex was analyzed using micro-CT for bone density and Masson's trichrome staining for histological examination., Results: The RANKL transient invalidation of RANKL stopped the molar root development and tooth eruption contrary to transgenic mice overexpressing RANK. The recruitment and the OC activity were strongly impacted., Discussion: This research is of direct clinical interest in understanding the pathology of eruption as indirect in establishing orthodontic treatment protocols for particular cases., (© EDP Sciences, SFODF, 2019.)

Objective: To assess the genetic and environmental influences on the variability of human third molar (M3) root mineralization stages via a twin study., Design: The study sample consisted of 162 same-sex twins (66 dizygotic and 96 monozygotic, mean age: 17.9 years) with normal growth and development. Panoramic radiographs were evaluated to assess root mineralization stages of the upper and lower third molars, using the method of Demirijian et al. (1973). Zygosity was established using 15 specific DNA markers., Results: Females developed their third molar roots earlier in life than males. Monozygotic twins (MZ) demonstrated higher intra-pair correlations for M3 root development stages than did DZ twins. An ACE model with additive genes, as well as common and specific environmental factors, provided the best explanation of variation in M3 root development. The mineralization of M3 roots showed highly additive genetic determination, varying from 60 to 63%, whereas a common environment contributed from 25 to 27%, and a specific environment only accounted 14% of the total variation, at most., Conclusions: A considerable proportion of the total variability of the third molar root mineralization rate can be attributed to additive genetic effects, while common and specific environmental effects have a smaller, yet significant, impact., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Several human dental traits typical of modern humans appear to be associated with the prolonged period of development that is a key human attribute. Understanding when, and in which early hominins, these dental traits first appeared is thus of strong interest. Using x-ray multiresolution synchrotron phase-contrast microtomography, we quantify dental growth and development in an archaic Homo juvenile from the Xujiayao site in northern China dating to 161,000-224,000 years or 104,000-125,000 years before present. Despite the archaic morphology of Xujiayao hominins, most aspects of dental development of this juvenile fall within modern human ranges (e.g., prolonged crown formation time and delayed first molar eruption). For its estimated age-at-death (6.5 years), its state of dental development is comparable to that of equivalently aged modern children. These findings suggest that several facets of modern human dental growth and development evolved in East Asia before the appearance of fully modern human morphology.

This study tests the relationship between third molar impaction and its concomitant effect on age estimation methods. Data were collected on radiographs of males analyzed in the Defense POW/MIA Accounting Agency Laboratory (n = 114). Radiographs of skeletonized individuals were scored for dental development, and age was assigned based on the appropriate ancestry-based method. Differences between identified age and estimated dental age were assessed to determine whether molar impaction affected root development and age estimations. Results indicate that impacted teeth tend to be underdeveloped and result in age estimates that are too low. While these results are of note to anthropologists and odontologists performing dental age estimates, more work is needed to explore the effect of impaction on development among a more diverse sample., (© 2018 American Academy of Forensic Sciences.)

Rationale: Oculofaciocardiodental syndrome (OFCD) patients who show radiculomegaly are very rare. We treated a new OFCD patient orthodontically, and performed longitudinal observation for 30 years. New findings, termed calcified-dental-papillae (CDPs) beneath open-apices (OAs) of developing radiculomegalies, pulp-stone-like-calcifications (PSLCs) and the process of radiculomegaly development were observed. A novel mutation of BCL-6 interacting corepressor (BCOR) was identified. Cone-beam-computed-tomography (CBCT) images of the radiculomegalies clarified their morphology., Patient Concerns: A female patient and her parents were referred to orthodontic clinic for alignment of the teeth., Diagnosis: A CDP that harbored bulbous-round-calcified-tissue in the dental papilla beneath the OA of a developing radiculomegaly was found radiographically. PSLCs were observed in the dental pulp. Genetic analysis revealed a novel mutation c.265G>A on Exon 4 and diagnosed as OFCD. CBCT images confirmed round-calcified-tissue and PSLC and that the length of an affected canine was 38.0 mm and calculated as +14.8SD. These novel findings were not observed in lateral incisors and molars., Interventions: Observation was performed for 29 years and 3 months including orthodontic treatment for 2 years and 9 months., Outcome: Longitudinal follow-up for 26 years and 7 months after the treatment revealed that the development of radiculomegaly every few months or years, CDPs beneath OAs and PSLCs were observed. CDPs, PSLCs, and OAs were associated with radiculomegaly. The patient and the affected teeth including aligned teeth showed no particular change after the completion of the radiculomegaly. CBCT images showed bulbous-calcified-tissue and PSLCs in the mature dental pulp associated with radiculomegaly., Lessons: The radiographical findings of CDP, OA and PSLC help early diagnose of OFCD and have importance for initiating orthodontic treatment until radiculomegaly completion.

The European Society of Endodontology and the American Association for Endodontists have released position statements and clinical considerations for regenerative endodontics. There is increasing literature on this field since the initial reports of Iwaya et al. (Dental Traumatology, 17, 2001, 185) and Banchs & Trope (Journal of Endodontics, 30, 2004, 196). Endogenous stem cells from an induced periapical bleeding and scaffolds using blood clot, platelet rich plasma or platelet-rich fibrin have been utilized in regenerative endodontics. This approach has been described as a 'paradigm shift' and considered the first treatment option for immature teeth with pulp necrosis. There are three treatment outcomes of regenerative endodontics; (i) resolution of clinical signs and symptoms; (ii) further root maturation; and (iii) return of neurogenesis. It is known that results are variable for these objectives, and true regeneration of the pulp/dentine complex is not achieved. Repair derived primarily from the periodontal and osseous tissues has been shown histologically. It is hoped that with the concept of tissue engineering, namely stem cells, scaffolds and signalling molecules, that true pulp regeneration is an achievable goal. This review discusses current knowledge as well as future directions for regenerative endodontics. Patient-centred outcomes such as tooth discolouration and possibly more appointments with the potential for adverse effects needs to be discussed with patients and parents. Based on the classification of Cvek (Endodontics and Dental Traumatology, 8, 1992, 45), it is proposed that regenerative endodontics should be considered for teeth with incomplete root formation although teeth with near or complete root formation may be more suited for conventional endodontic therapy or MTA barrier techniques. However, much is still not known about clinical and biological aspects of regenerative endodontics., (© 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Trio, the Rho guanine nucleotide exchange factor (Rho-GEF), plays diverse roles in cell migration, cell axon guidance and cytoskeleton reorganization. Conserved during evolution, Trio encodes two guanine nucleotide exchange factor domains (GEFs) and activates small GTPases. The Rho-family small GTPases RhoA and Rac1, which are target molecules of Trio, have been described to engage in craniofacial development and tooth formation. However, the exact role of Trio in tooth development remains elusive. In this study, we generated Wnt1-cre;Trio fl/fl mice to address the potential function of Trio in tooth development. Wnt1-cre;Trio fl/fl mice showed short root deformity as well as decreased expression of odontogenic makers such as RUNX2, OSX, OCN, and OPN. In vitro, Trio was silenced in human stem cells of dental papilla (SCAPs). Compared with the control group, the proliferation and migration ability in the experimental group was disrupted. After knocking down Trio in SCAPs, the cells showed phenotypes of poor odontogenic differentiation and weak mineralized nodules. To study the underlying mechanism, we investigated the p38 MAPK pathway and found that loss of Trio blocked the cascade transduction of p38 MAPK signaling. In conclusion, we identified Trio as a novel coordinator in regulating root development and clarified its relevant molecular events., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: The outcomes of an immature tooth with necrotic pulp treated with regenerative endodontic procedures (REPs) were assessed clinically and radiographically. Root maturation is an important outcome of REPs, and several radiographic measurement methods have been used to measure this. The aim of this study was to compare radiographic measurement methods, measuring root maturation in immature teeth with necrotic pulp treated with REPs., Methods: Seventy-one radiographic images of REP cases were measured and compared using 3 radiographic measurement methods described by Bose et al (2009), Alobaid et al (2014), and Flake et al (2014). The intraclass correlation coefficient values were evaluated using the intra- and interobserver reliability test and the effect of the stage of root development., Results: The intra- and interobserver reliability for Alobaid et al's method and Flake et al's method were slightly higher than Bose et al's method as quantified by the intraclass correlation coefficient without a significant difference (P > .05). The stage of root development did not affect the reliability of the measurement methods. A high level of agreement was found among the 3 stages of root development for all 3 quantitative radiographic measurement methods., Conclusions: All 3 quantitative radiographic measurement methods exhibited high agreement regarding reliability. The stage of root development did not have an impact on the reliability of the measurement methods., (Copyright © 2018 American Association of Endodontists. All rights reserved.)

Introduction: A regenerative endodontic procedure (REP) is a biologically based treatment to functionally replace the pulp of infected immature permanent teeth. The purpose of this retrospective case series was to assess the outcome of REPs of infected immature permanent teeth in terms of periapical bone healing (PBH), root development (RD), and pulp vitality., Methods: Five patients (1 tooth/patient) who had undergone a REP based on the cell homing concept were recalled 3, 6, 12, 24, and 36 months postoperatively. At each recall session, clinical and periapical radiographic (PR) investigations were performed. Cone-beam computed tomographic (CBCT) imaging was taken before and 36 months after REPs. Qualitative and quantitative PR assessments were performed on the teeth that underwent REPs. Quantitative CBCT analyses were performed on the teeth that underwent REP and contralateral teeth., Results: At each recall session, all teeth were asymptomatic but reacted negatively on carbon dioxide snow and electrical pulp testing. All teeth that underwent a REP showed complete PBH and further RD on PR and CBCT assessments when comparing the baseline with the final recall radiographs. CBCT analyses indicated increases in root hard tissue volume and RL for all teeth that underwent a REP, but they were 5 and 3 times less, respectively, than the contralateral teeth. The postoperative CBCT images presented bone ingrowth inside the root canal, calcification, or nonuniform RD., Conclusions: Thirty-six months after the REPs (based on the cell homing concept), this RCS resulted radiographically and clinically in functional and asymptomatic teeth with complete PBH and continued reparative RD. CBCT quantitative measurements and qualitative root development observations are more reliable and accurate than PR analysis., (Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

The bone morphogenetic protein (BMP) family is an important factor in the regulation of cell ular life activities and in the development of almost all tissues. BMP-mediated signaling plays an important role in tooth root development, which is a part of tooth development. Epithelial and mesenchymal interactions are involved in tooth root development, but the BMP signaling pathway has a different effect on tooth root development in epithelial and mesenchymal. This review summarizes the advances of BMP signaling in tooth root development.

Objectives: To examine the relationship between tooth length and growth hormone receptor (GHR) gene variants in a healthy Japanese population., Materials and Methods: The subjects consisted of 193 Japanese adults (69 men, 124 women), aged 13 to 56 years. Genomic DNA was extracted from saliva and genotyped GHR rs6184 and rs6180 variants using the Taqman genotyping. Computed tomography (CT) images were acquired using a dental cone-beam CT scanner and reconstructed using open-source OsiriX medical image processing software. The maxillary (upper; U) and mandibular (lower, L) central incisors (1), lateral incisors (2), canines (3), first premolars (4), second premolars (5), first molars (6), and second premolars (7) were evaluated. Teeth were assessed for crown height (CH), root length (RL), overall tooth length (C+R), and crown to root ratio (C/R). The relationships between GHR variants and CH, RL, C+R, and C/R were statistically examined., Results: The GHR variant rs6184 was associated with the root lengths and tooth length for the upper and lower lateral incisors and upper canines (U2 RL; U3 RL, C+R; L2 RL [ P < .05])., Conclusions: The results indicate that the GHR rs6184 variant is associated with tooth length and ratio dimensions in a Japanese cohort. Further studies utilizing a larger sample size are needed to confirm this finding.

The tooth root is essential for normal tooth physiological function. Studies on mice with mutations or targeted gene deletions revealed that osteoclasts (OCs) play an important role in tooth root development. However, knowledge on the cellular and molecular mechanism underlying how OCs mediate root formation is limited. During bone formation, growth factors (e.g. Insulin-like growth factor-1, IGF-1) liberated from bone matrix by osteoclastic bone resorption stimulate osteoblast differentiation. Thus, we hypothesize that OC-osteoblast coupling may also apply to OC-odontoblast coupling; therefore OCs may have a direct impact on odontoblast differentiation through the release of growth factor(s) from bone matrix, and consequently regulate tooth root formation. To test this hypothesis, we used a receptor activator of NF-κB ligand (RANKL) knockout mouse model in which OC differentiation and function was entirely blocked. We found that molar root formation and tooth eruption were defective in RANKL -/- mice. Disrupted elongation and disorganization of Hertwig's epithelial root sheath (HERS) was observed in RANKL -/- mice. Reduced expression of nuclear factor I C (NFIC), osterix, and dentin sialoprotein, markers essential for radicular (root) odontogenic cell differentiation indicated that odontoblast differentiation was disrupted in RANKL deficient mice likely contributing to the defect in root formation. Moreover, down-regulation of IGF/AKT/mTOR activity in odontoblast indicated that IGF signaling transduction in odontoblasts of the mutant mice was impaired. Treating odontoblast cells in vitro with conditioned medium from RANKL -/- OCs cultured on bone slices resulted in inhibition of odontoblast differentiation. Moreover, depletion of IGF-1 in bone resorption-conditioned medium (BRCM) from wild-type (WT) OC significantly compromised the ability of WT osteoclastic BRCM to induce odontoblast differentiation while addition of IGF-1 into RANKL -/- osteoclastic BRCM rescued impaired odontoblast differentiation, confirming that root and eruption defect in RANKL deficiency mice may result from failure of releasing of IGF-1 from bone matrix through OC bone resorption. These results suggest that OCs are important for odontoblast differentiation and tooth root formation, possibly through IGF/AKT/mTOR signaling mediated by cell-bone matrix interaction. These findings provide significant insights into regulatory mechanism of tooth root development, and also lay the foundation for root regeneration studies., (Copyright © 2017. Published by Elsevier Inc.)

Estimating chronological age accurately in young adults is difficult and additional methods are required to increase the accuracy. This study explored a new semi-automated method to assess shape change of third cervical vertebra (C3) with age in the living; comparing this as a method to determine whether individuals could be categorised into being less than 18 years of age (<18), or at least 18 years of age (≥18) with tooth formation of the second and third mandibular molars (M2 and M3). The sample was panoramic and lateral skull radiographs of 174 dental patients (78 males, 96 females aged 15-22 years). Twelve variables were compared in two age categories: younger than 18 and at least 18 years of age in males and females separately using a t-test. Tooth formation of M2 and M3 was assessed. Mean values of eight variables of C3 in males and one variable in females were significantly different between the two age categories (p < 0.05). Results for males showed that the best age indicator for age ≥18 was the ratio between height and width of C3 and for females, the ratio between diagonals. Results for molars showed that M2 was mature in 69% of males and 83% of females, within the expected age range of 14-16 years. M3 was highly variable ranging from stages 6-14 for both; M3 was missing in 24% of males and 28% of females and mature in 14% of males and 15% of females. The conclusion was that shape change of C3 has potential as an additional method to group individuals <18 and ≥ 18 years of age., (Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Background: The incisors and molars play a major role in the formation and function of permanent dentition. Much research has been devoted to investigating the eruption of teeth and their root development., Aim: To study the root development of permanent incisors and mandibular molars in correlation with treatment plan and proper treatment protocols., Materials and Methods: The Demirjian's method was used to assess the root development of incisors and mandibular molars in children between 7 and 12 years old., Results: In 7-year-old children most of the lower first mandibular molars (76%) had complete root length, but open apices. Eighty-two percent of the roots of the first mandibular molars of the 8-year-old children and 54% of these molars of the 9-year-old children were with open apices. The first mandibular molars had incomplete roots in the 10-year-olds (6%) and even in the 11-year-old children (4%). We detected Stage E in 32% of the 10-year-olds and in 24% of the 11-year-old children. Even in 12-year-old children we found Stage E in 4% of them from their panoramic X-rays. We detected complete root development in all of the children at the age of 12., Conclusions: Dental practitioners have to wait until the age of 10, 11 and even 12 to extract the first molars, when the furcation is formed. Proper clinical examination and diagnostic radiographs should be done before the beginning of the treatment of molars and incisors at the age between 7 and 12.

Tooth and bone are major tissues involved in physiological calcification in the body, and they use similar molecular pathways for development, homeostasis, and regeneration. Harmine (HMN) is a natural small compound that stimulates osteoblast differentiation in vitro and in vivo. Here we examined the biological effect of HMN on the postnatal development of molar tooth roots and periodontal tissues. HMN supported the formation of tooth roots and periodontal tissues in developing tooth germs. In tooth germ organ culture, HMN promoted the elongation of Hertwig's epithelial root sheath (HERS) and stimulated cell proliferation in HERS and dental follicle-derived tissues, including dental papillae and dental follicles. HMN stimulated cell proliferation and cell movement of HERS-derived cells without mesenchymal cells in vitro and directly induced the phosphorylation of SMAD1/5/8 protein in HERS-derived cells. Our results indicated that HMN was the first natural small compound to stimulate postnatal development of tooth germs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate the crown and root development in patients with cleft lip and palate using medical software programmes., Materials and Methods: In our study, 25 patients with mixed dentition unilateral cleft lip and palate were examined with cone-beam computed tomography (CBCT). The tomography images obtained as high resolution medical images on the computer control system (MIMICS 15.0, Materialise, Leuven, Belgium and SOLIDWORKS 2014 Premium, Concord, Massachusetts) were converted to three-dimensional volumetric images. These three-dimensional images of the cleft on the sides of the teeth in the crown and root growth were measured by mesiodistal length and crown/root rate with volume and area. These measurements were compared with a control group of healthy individuals., Results: There were no statistically significant differences in the volume, surface area and MD size, crown/root ratio of central incisor, canine, first premolar and second premolar teeth within defect, and healthy teeth. However, it was found that there was a significant difference between the volume, surface area and MD size, and crown/root ratio of the lateral teeth in each group., Conclusion: In particular, among patients with cleft lip and palate, on obtaining a solid model of the tooth structure by using these programs, tooth development can be examined in more detail, diagnosis can be made more reliable, as well as in treatment planning. We believe that these programs can be used to resolve certain limitations such as a lack of an application to be used in routine dental treatment and in particular the need to do more study., Competing Interests: There are no conflicts of interest.

Tooth eruption is characterized by a concert of mechanisms that result in the emergence of teeth in the oral cavity. Genetic variants seem to regulate this process and the formation of a gingival sulcus around the teeth. Interindividual variability in the response to microbial triggers in the sulcus plays an important role in the onset and progression of periodontal diseases. Host genetic variants can influence this variability, affecting the response of the host to the subgingival biofilm. Genetic factors affecting tooth eruption could potentially influence susceptibility to periodontal diseases and, specifically, susceptibility to localized aggressive periodontitis. This review aims to discuss the evidence available for the role of host genetic variants in tooth eruption and to and to give some directions for prospective research in this topic., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The tooth root transmits and balances occlusal forces through the periodontium to the alveolar bone. The periodontium, including the gingiva, the periodontal ligament, the cementum and the partial alveolar bone, derives from the dental follicle (DF), except for the gingiva. In the early developmental stages, the DF surrounds the tooth germ as a sphere and functions to promote tooth eruption. However, the morphological dynamics and factors regulating the differentiation of the DF during root elongation remain largely unknown. Miniature pigs are regarded as a useful experimental animal for modeling in craniofacial research because they are similar to humans with respect to dentition and mandible anatomy. In the present study, we used the third deciduous incisor of miniature pig as the model to investigate the factors influencing DF differentiation during root development. We found that the DF was shaped like a crescent and was located between the root apical and the alveolar bone. The expression levels of WNT5a, β-Catenin, and COL-I gradually increased from the center of the DF (beneath the apical foramen) to the lateral coronal corner, where the DF differentiates into the periodontium. To determine the potential regulatory role of the apical papilla on DF cell differentiation, we co-cultured dental follicle stem cells (DFSCs) with stem cells of the apical papilla (SCAPs). The osteogenesis and fibrogenesis abilities of DFSCs were inhibited when being co-cultured with SCAPs, suggesting that the fate of the DF can be regulated by signals from the apical papilla. The apical papilla may sustain the undifferentiated status of DFSCs before root development finishes. These data yield insight into the interaction between the root apex and surrounding DF tissues in root and periodontium development and shed light on the future study of root regeneration in large mammals., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.