Tooth eruption is a localised event whereby the signals for eruption for a given tooth are synthesised in the dental follicle of that tooth with a possible cross talk of signals coming from the adjacent stellate reticulum. The eruption process requires alveolar bone resorption that is primarily regulated by the dental follicle. This is reflected by the fact that failures of eruption often can be traced to either osteoclast deficiencies or to dental follicle abnormalities. Recent advances in application of molecular techniques to animal models allowed for better understanding of gene regulatory events involved in the physiology of tooth eruption. This article attempts to consolidate and organise the facts that offshoot from animal studies.
Tooth Eruption ; Dental Sac ; Molecular Biology

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1^-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Animals ; Humans ; Mice ; Rats ; Bone Remodeling/physiology* ; Caspase 1 ; Periodontal Ligament ; Pyroptosis ; Tooth Movement Techniques

Background: Orthodontic tooth movement occurs due to bone resorption and apposition on the pressure and tension side of the PDL. The transcription factors associated with osteoclast differentiation are NFATc1 while osteoblast differentiation is associated with RUNX2. The optimum force of orthodontic tooth movement can move the teeth to the desired position, without causing discomfort and tissue damage to the patient. Objective: This study aims to analyse the effect of gradually increasing force on orthodontic tooth movement (by evaluating the NFATc1 and RUNX2 expression) in rats. Methods: This research is an in vivo experimental study with a post-test control group design. Twenty-eight healthy male adult Wistar rats (Rattus novergicus) aged 4-5 months with body weights 200-250 g rats were divided into seven study groups. Treatment groups in this study are given the force (by applying a closed coil spring between the maxillary central incisor and the maxillary first molar) of 5 g, 5-10 g, 10 g, and 10-20 g with the duration of treatment in 14 and 28 days. After the treatment day was finished, the alveolar bone tissue was isolated and investigated by immunohistochemical methods. Results: Indicate a significant difference between the control and all treatment groups of NFATc1 (p=0.003; p=0.000; p:0.010; p=0.001; p=0.001; p=0.000) and RUNX2 with groups of 10 g/14 days, 10 g/28 days, 5 g/28 days, 10 g/14 days,10-20 g/28 days (p=0.001; p=0.000; p=0.000; p=0.017; p=0.014; p=0.000) values. Conclusion Gradually increasing force affects orthodontic tooth movement by inducing bone resorption (high expression of NFATc1) in the pressure area and bone apposition (high expression of RUNX2) in the tension area. Applying heavy force by initially applying light force could inhibit hyalinization.
Orthodontic Tooth Movement ; Tooth Movement Techniques

The biomolecular mechanisms that regulate tooth root development and odontoblast differentiation are poorly understood. We found that Atp6i deficient mice (Atp6i^-/-) arrested tooth root formation, indicated by truncated Hertwig's epithelial root sheath (HERS) progression. Furthermore, Atp6i deficiency significantly reduced the proliferation and differentiation of radicular odontogenic cells responsible for root formation. Atp6i^-/- mice had largely decreased expression of odontoblast differentiation marker gene expression profiles (Col1a1, Nfic, Dspp, and Osx) in the alveolar bone. Atp6i^-/- mice sample RNA-seq analysis results showed decreased expression levels of odontoblast markers. Additionally, there was a significant reduction in Smad2/3 activation, inhibiting transforming growth factor-β (TGF-β) signaling in Atp6i^-/- odontoblasts. Through treating pulp precursor cells with Atp6i^-/- or wild-type OC bone resorption-conditioned medium, we found the latter medium to promote odontoblast differentiation, as shown by increased odontoblast differentiation marker genes expression (Nfic, Dspp, Osx, and Runx2). This increased expression was significantly blocked by anti-TGF-β1 antibody neutralization, whereas odontoblast differentiation and Smad2/3 activation were significantly attenuated by Atp6i^-/- OC conditioned medium. Importantly, ectopic TGF-β1 partially rescued root development and root dentin deposition of Atp6i^-/- mice tooth germs were transplanted under mouse kidney capsules. Collectively, our novel data shows that the prevention of TGF-β1 release from the alveolar bone matrix due to OC dysfunction may lead to osteopetrosis-associated root formation via impaired radicular odontoblast differentiation. As such, this study uncovers TGF-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation and may contribute to future therapeutic approaches to tooth root regeneration.
Female ; Animals ; Mice ; Transforming Growth Factor beta1 ; Odontoblasts ; Culture Media, Conditioned ; Cell Differentiation ; Signal Transduction ; Disease Models, Animal ; Tooth Root

X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads to hypophosphatemia and impaired mineralization of bone and teeth. The clinical manifestations of XLH include a high prevalence of dental abscesses and periodontal disease, likely driven by poorly formed structures of the dentoalveolar complex, including the alveolar bone, cementum, dentin, and periodontal ligament. Our previous studies have demonstrated that sclerostin antibody (Scl-Ab) treatment improves phosphate homeostasis, and increases long bone mass, strength, and mineralization in the Hyp mouse model of XLH. In the current study, we investigated whether Scl-Ab impacts the dentoalveolar structures of Hyp mice. Male and female wild-type and Hyp littermates were injected with 25 mg·kg^-1 of vehicle or Scl-Ab twice weekly beginning at 12 weeks of age and euthanized at 20 weeks of age. Scl-Ab increased alveolar bone mass in both male and female mice and alveolar tissue mineral density in the male mice. The positive effects of Scl-Ab were consistent with an increase in the fraction of active (nonphosphorylated) β-catenin, dentin matrix protein 1 (DMP1) and osteopontin stained alveolar osteocytes. Scl-Ab had no effect on the mass and mineralization of dentin, enamel, acellular or cellular cementum. There was a nonsignificant trend toward increased periodontal ligament (PDL) attachment fraction within the Hyp mice. Additional PDL fiber structural parameters were not affected by Scl-Ab. The current study demonstrates that Scl-Ab can improve alveolar bone in adult Hyp mice.
Mice ; Male ; Female ; Animals ; Familial Hypophosphatemic Rickets/metabolism* ; Bone and Bones/metabolism* ; Tooth/metabolism* ; Periodontal Ligament/metabolism*

Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation. The initiation of Hertwig's epithelial root sheath (HERS) induces odontoblast differentiation and the subsequent radicular dentin deposition. Precisely controlled signaling pathways modulate the behaviors of HERS and the fates of dental mesenchymal stem cells (DMSCs). Disruptions in these pathways lead to defects in root development, such as shortened roots and furcation abnormalities. Advances in dental stem cells, biomaterials, and bioprinting show immense promise for bioengineered tooth root regeneration. However, replicating the developmental intricacies of odontogenesis has not been resolved in clinical treatment and remains a major challenge in this field. Ongoing research focusing on the mechanisms of root development, advanced biomaterials, and manufacturing techniques will enable next-generation biological root regeneration that restores the physiological structure and function of the tooth root. This review summarizes recent discoveries in the underlying mechanisms governing root ontogeny and discusses some recent key findings in developing of new biologically based dental therapies.
Female ; Humans ; Tooth Root/metabolism* ; Odontogenesis ; Epithelial Cells ; Cell Differentiation ; Biocompatible Materials/metabolism*

Digital guided therapy (DGT) has been advocated as a contemporary computer-aided technique for treating endodontic diseases in recent decades. The concept of DGT for endodontic diseases is categorized into static guided endodontics (SGE), necessitating a meticulously designed template, and dynamic guided endodontics (DGE), which utilizes an optical triangulation tracking system. Based on cone-beam computed tomography (CBCT) images superimposed with or without oral scan (OS) data, a virtual template is crafted through software and subsequently translated into a 3-dimensional (3D) printing for SGE, while the system guides the drilling path with a real-time navigation in DGE. DGT was reported to resolve a series of challenging endodontic cases, including teeth with pulp obliteration, teeth with anatomical abnormalities, teeth requiring retreatment, posterior teeth needing endodontic microsurgery, and tooth autotransplantation. Case reports and basic researches all demonstrate that DGT stand as a precise, time-saving, and minimally invasive approach in contrast to conventional freehand method. This expert consensus mainly introduces the case selection, general workflow, evaluation, and impact factor of DGT, which could provide an alternative working strategy in endodontic treatment.
Humans ; Consensus ; Endodontics/methods* ; Tooth ; Printing, Three-Dimensional ; Dental Care ; Cone-Beam Computed Tomography ; Root Canal Therapy

OBJECTIVES: This study aimed to construct the finite element model of the mandibular first molar with the invisible appliance and explore the dentition movement characteristics of the mandibular first molar when using micro-implant anchorage and different initial positions of the first molar. METHODS: Models of the mandible, tooth, periodontal membrane, and invisible appliance were constructed using cone beam computed tomography (CBCT) data. The two groups were divided into the non-anchorage group and the micro-implant group (between the roots of the first molar and the second molar) based on whether the elastic traction of the micro-implant was assisted or not. The two groups were divided into the following conditions based on the starting position of the first molar: Working condition 1: the distance between the first molar and the second premolar was 0 mm; working condition 2: the distance between the first molar and the second premolar was 1 mm; working condition 3: the distance between the first molar and the second premolar was 2 mm; working condition 4: the distance between the first molar and the second premolar was 3 mm. The data characte-ristics of total displacement and displacement in each direction of dentition were analyzed. RESULTS: In the non-ancho-rage group, all the other teeth showed reverse movement except for the first molar which was moved distally. Meanwhile, in the micro-implant group, except for a small amount of mesial movement of the second molar in wor-king condition 1, the whole dentition in other working conditions presented distal movement and anterior teeth showed lingual movement, among which the distal displacement of the first molar in working condition 4 was the largest. With the change of the initial position of the first molar to the distal, the movement of the first molar to the distal, the premolar to the mesial, and the anterior to the lip increased, while the movement of the second molar to the mesial decreased. CONCLUSIONS The micro-implant can effectively protect the anterior anchorage, increase the expression rate of molar distancing, and avoid the round-trip movement of the second molar. The initial position of the first molar movement is related to the amount of distancing and the remaining tooth movement.
Finite Element Analysis ; Molar ; Bicuspid ; Periodontal Ligament ; Tooth Movement Techniques/methods* ; Orthodontic Appliances, Removable

OBJECTIVES: This study aimed to investigate the feasibility of measuring the soft tissue height of bone cristae around implant by digital method. METHODS: A total of 36 patients with dental implants were selected from the Dental Medicine Center of the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from August 2022 to December 2022. A total of 43 dental implants were enrolled. All postoperative cone beam CT (CBCT) imaging data and intraoral digital impressions obtained before surgery were immediately obtained by the patients on the day of completion of oral implant surgery and they were imported into oral implant surgery planning software for image fitting. Then, virtual implants of the same specification were placed in the planting area, and the implant position was adjusted to overlap with the implant shadow in the CBCT image. Supracrestal tissue height (STH) was measured at the implant view interface (digital group). During the operation, implant holes were prepared step by step in accordance with the standard preparation method, and implants were implanted. The upper edge of the implant was flushed with the crest of the alveolar ridge. STH was measured by perio-dontal probing (periodontal probe group). Paired t-test was used to compare the STH differences between the digital and periodontal probe groups. Bland-Altman test was used to analyze the consistency of the two methods. Intra-group correlation coefficient (ICC) was used to verify the reliability of the results measured by different surveyors using di-gital methods. RESULTS: No statistical significance was observed in the STH difference between the two methods (P>0.05). Bland-Altman test showed good consistency between the two methods, but the measurement of mandibular posterior teeth showed that the results of periodontal probe were greater than those of digital method. The ICC and 95%CI of the STH results measured digitally by different surveyors are 0.992 (0.986-0.996). CONCLUSIONS The digital me-thod is in good agreement with the periodontal probe method in measuring the soft tissue height of the bone cristae around the implant.
Humans ; Alveolar Process/diagnostic imaging* ; Cone-Beam Computed Tomography/methods* ; Dental Implants ; Feasibility Studies ; Reproducibility of Results ; Tooth/diagnostic imaging*

OBJECTIVES: This study aimed to evaluate the efficacy and long-term stability of tunnel technique (TUN) and coronally advanced flap (CAF) combined with connective tissue graft (CTG) in treating gingival recession. METHODS: Databases including PubMed, Web of Science, Embase, and CNKI were electronically searched to collect randomized controlled trial (RCT) of CAF+CTG compared to TUN+CTG in the treatment of Miller class Ⅰ or Ⅱ gingival recession on September 1, 2022. RESULTS: There were 8 RCTs with 305 patients (454 recession sites) participating. The results of the Meta-analysis revealed that, in terms of mean root coverage (MRC) of main indicators, no significant difference was found between the CAF group and the TUN group in both short- and long-term results, which were [MD: 1.45%, 95%CI (-2.93%, 5.82%), P=0.52] and [MD: -0.70%, 95%CI (-6.41%, 5.00%), P=0.81]. However, the CAF group outperformed the TUN group in the long term [MD: 5.69%, 95%CI (0.87%, 10.50%), P=0.02], and the results of complete root coverage (CRC) analysis were similar to those of MRC. In the short term, the TUN group grew keratinized gingiva significantly faster than the CAF group [MD: -0.38 mm, 95%CI (-0.67 mm, -0.10 mm), P=0.008]. Long-term findings revealed no significant difference between the two groups [MD: -0.26 mm, 95%CI (-0.94 mm, 0.43 mm), P=0.46]. The TUN group's secondary index root coverage esthetic score (RES) was statistically significantly higher than the CAF group's [MD: 0.62, 95%CI (0.28, 0.96), P=0.000 3]. Given that there were few results included in the literature and the heterogeneity was too great, no significant difference was observed in the postoperative VAS pain index score [MD: 0.53, 95%CI (-1.96, 3.03), P=0.68]. CONCLUSIONS This study discovered that both CAF+CTG and TUN+CTG can achieve good root coverage in treating gingival recession, with CAF outperforming TUN and both groups achie-ving good long-term stability. After the operation, the TUN group had a higher RES than the CAF group. Given the limitations of this study, more high-quality studies are needed in the future to demonstrate the efficacy of TUN in gingival retraction surgery.
Humans ; Gingival Recession/surgery* ; Treatment Outcome ; Tooth Root ; Esthetics, Dental ; Gingiva/surgery*