The transforming growth factor β (TGFβ) superfamily is a master regulator of development, adult homeostasis, and wound repair. Dysregulated TGFβ signaling can lead to cancer, fibrosis, and musculoskeletal malformations. We previously demonstrated that TGFβ receptor 2 (Tgfbr2) signaling regulates odontoblast differentiation, dentin mineralization, root elongation, and sensory innervation during tooth development. Sensory innervation also modulates the homeostasis and repair response in adult teeth. We hypothesized that Tgfbr2 regulates the neuro-pulpal responses to dentin injury. To test this, we performed a shallow dentin injury with a timed deletion of Tgfbr2 in the dental pulp mesenchyme of mice and analyzed the levels of tertiary dentin and calcitonin gene-related peptide (CGRP) axon sprouting. Microcomputed tomography imaging and histology indicated lower dentin volume in Tgfbr2cko M1s compared to WT M1s 21 days post-injury, but the volume was comparable by day 56. Immunofluorescent imaging of peptidergic afferents demonstrated that the duration of axon sprouting was longer in injured Tgfbr2cko compared to WT M1s. Thus, CGRP+ sensory afferents may provide Tgfbr2-deficient odontoblasts with compensatory signals for healing. Harnessing these neuro-pulpal signals has the potential to guide the development of treatments for enhanced dental healing and to help patients with TGFβ-related diseases.

Dentin is a permeable and complex tubular composite formed by the mineralization of predentin that mineralization and repair are of considerable clinical interest during dentin homeostasis. The role of Vdr, a receptor of vitamin D, in dentin homeostasis remains unexplored. The aim of the present study was to assess the impact of Vdr on predentin mineralization and dental repair. Vdr-knockout (Vdr-/-) mice models were constructed; histology and immunohistochemistry analyses were conducted for both WT and Vdr-/- mice. The finding revealed a thicker predentin in Vdr-/- mice, characterized by higher expression of biglycan and decorin. A dental injury model was employed to observe tertiary dentin formation in Vdr-/- mice with dental injuries. Results showed that tertiary dentin was harder to form in Vdr-/- mice with dental injury. Over time, heightened pulp invasion was observed at the injury site in Vdr-/- mice. Expression of biglycan and decorin was reduced in the predentin at the injury site in the Vdr-/- mice by immunohistochemistry. Taken together, our results imply that Vdr plays a regulatory role in predentin mineralization and tertiary dentin formation during dentin homeostasis.

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

Regenerative dentistry has rapidly progressed since the advancement of stem cell biology and material science. However, more emphasis has been placed on the success of tissue formation than on how well the newly generated tissue retains the original structure and function. Once dentin is lost, tertiary dentinogenesis can be induced by new odontoblastic differentiation or re-activation of existing odontoblasts. The characteristic morphology of odontoblasts generates the tubular nature of dentin, which is a reservoir of fluid, ions, and a number of growth factors, and protects the inner pulp tissue. Therefore, understanding the dynamic but delicate process of new dentin formation by odontoblasts, or odontoblast-like cells, following dentinal defects is crucial. In this regard, various efforts have been conducted to identify novel molecules and materials that can promote the regeneration of dentin with strength and longevity. In this review, we focus on recent progress in dentin regeneration research with biological molecules identified, and discuss its potential in future clinical applications.

OBJECTIVE: This study aimed to evaluate changes on root canal morphology in patients with different ages using micro-CT technology.
METHODS: Mandibular first molars (n = 150) were scanned at a pixel size of 13.68 µm, categorized into 3 groups according to patient\'s age and analyzed regarding configuration, orifices, apical foramina, root length, canal volume, and surface area. Morphological 2D and 3D parameters were evaluated in distal roots with Type I configuration (n = 109) as well as the morphology of isthmuses Types I and III in 68 mesial roots. One-way ANOVA post hoc Tukey and Kruskal-Wallis tests were used for statistical analyses (α = 5%).
RESULTS: A great variation in the canal configuration was found. No difference was observed in roots\' length (p > 0.05). Canal volume reduced with age (p < 0.05), while surface area increased (p < 0.05) in patients ≤ 30 years. There was no difference in canal/root length, area, and from foramen to the apex in distal roots with Type I configuration (p > 0.05), but 2D and 3D parameters significantly decreased with age (p < 0.05). Overall, the diameter of the isthmuses\' roof reduced with age (p < 0.05). In patients ≥ 31 years with Type III isthmus the distance from the isthmus floor to the foramen of the mesiolingual canal also decreased (p < 0.05).
CONCLUSIONS: Overall, the internal morphology of the mesial roots of mandibular first molars was more affected by aging than distal canals. The most relevant tested parameter that significantly reduced in both roots was the volume of the root canal systems.
CONCLUSIONS: A detailed evaluation of fine anatomical aspects of the root canal system of mandibular first molars of patients with different ages showed that the internal morphology of mesial roots is more affected by aging than distal canals.

The aim of this study was to conduct a three-dimensional (3D) evaluation of radiographic changes after indirect pulp capping (IPC) with silver diamine fluoride (SDF) with or without potassium iodide (KI) and resin-modified glass ionomer cement (RMGIC) in deep carious young permanent molars using cone-beam computed tomography (CBCT). 108 first permanent molars with deep occlusal cavitated caries lesions, in forty-nine 6- to 9-year-old children, were randomly allocated to one of 3 groups (n = 36) and treated with SDF+KI, SDF, and RMGIC as IPC materials. CBCT scans were taken at 0 and 12 months to assess tertiary dentin formation (volume and grey level intensity), increase in root length, and pathological changes such as secondary caries, periapical radiolucency, internal resorption, and obliteration of the pulp. The 3D image analysis procedures were performed using ITK-SNAP and 3D Slicer CMF. Comparisons were made using analysis of variance with a fixed effect for treatment and random effects for patient and patient-by-treatment to account for within-patient correlations. A two-sided 5% significance level was used. There were no significant differences among the three groups regarding tertiary dentin volume (p = 0.712) and grey level intensity (p = 0.660), increase in root length (p = 0.365), prevention of secondary caries (p = 0.63), and periapical radiolucency (p = 0.80) in the analysed 69 CBCT scans. The study did not find differences among the groups regarding quality and quantity of tertiary dentin formed, increase in root length, absence of secondary caries, and other signs of failure as shown by CBCT. Clinical Significance: The results show no significant differences in radiographic outcomes (quality and quantity of tertiary dentin formed, increase in root length, absence of secondary caries, and other signs of failure) when using SDF+KI, SDF, and RMGIC in IPC. The results of this study can help guide treatment decision-making regarding use of SDF and SDF+KI as IPC materials in deep cavitated lesions.

Dentin hypersensitivity is a painful response to external stimuli applied to exposed dentinal tubules. Various toothpastes with active desensitizing ingredients for the relief of dentin hypersensitivity are commercially available. However, data from several studies suggest that the effects of desensitizing toothpastes are unstable and brief. This study aimed to investigate the effect of toothpastes containing CPNE7-derived oligopeptide (CPNE7-DP) and other active desensitizing ingredients in the dentin microleakage, tubule occlusion and tertiary dentin formation.
Using scanning electron microscopy (SEM), we evaluated the patency of dentinal tubules on the surface of human dentin disks after brushing experiments with the various toothpastes. Dentin was histologically evaluated in a hypersensitivity model of canine teeth, after the exposed dentin area was brushed for 6 weeks. The toothpaste used in group 1 (control) did not contain any desensitizing ingredients; that used in group 2 contained CPNE7-DP; Colgate Sensitive was used in group 3; and Sensodyne Rapid Relief was used in group 4. Finally, we conducted microleakage analysis to investigate the dentin sealing effect. The microleakage analysis data were subjected to one-way ANOVA and post-hoc Tukey tests (alpha = 0.05).
In the SEM images, all four groups of teeth exhibited partial occlusion of the dentinal tubules on the tooth surface. In the in vivo hypersensitivity model, group 2 exhibited a newly formed tertiary dentin, whereas no new hard tissue formation was observed in groups 1, 3, and 4. Microleakage analysis revealed that the volume of dentinal fluid flow was significantly smaller in group 2 than in group 1.
These results indicate that CPNE7-DP is a promising active ingredient with long-term dentin sealing effects.

Inflammatory diseases of the teeth and periodontium are widespread and are frequent secondary diagnoses in head and neck examinations. Periapical inflammation can be the cause of sinusitis or abscess formation in the oral and maxillofacial region. Early detection is important for the patient\'s course of treatment. For further diagnostics, a dental presentation should be carried out. Dental radiological examinations, such as panoramic radiographs and dental films are used for specific diagnostics. This article is intended to provide an overview of the different stages of caries, the most important inflammatory dental changes and their most frequent differential diagnoses.
UNASSIGNED: Entzündliche Erkrankungen der Zähne und des Zahnhalteapparats sind weit verbreitet und häufige Nebendiagnosen bei Kopf-Hals-Untersuchungen. Eine periapikale Entzündung kann Ursache für Sinusitiden oder Abszesse im Mund‑, Kiefer- und Gesichtsbereich sein. Frühzeitiges Erkennen ist für den Behandlungsverlauf des Patienten wichtig. Zur weiteren Abklärung sollte eine zahnärztliche Vorstellung erfolgen. Zur gezielten Diagnostik finden dabei dentalradiologische Untersuchungen wie die Panoramaschichtaufnahme (PSA) und der Zahnfilm Anwendung. Dieser Artikel soll eine Übersicht über verschiedene Stadien der Karies, die wichtigsten entzündlichen Zahnveränderungen und ihre häufigsten Differenzialdiagnosen geben.

The present paper is the first article providing a systematic literature review on the visualization of tertiary dentin influenced by modern bioactive materials in CBCT and micro-CT. Six database searches of studies on tertiary dentin visualization using CBCT produced 622 records in total, and the search of the studies on tertiary dentin using micro-CT produced 502 records in total. The results were thoroughly selected considering the inclusion criteria, and five research papers using CBCT and nine research papers using micro-CT for visualization of tertiary dentin were eventually qualified for the analysis. All the non-randomized and randomized studies presented good and high levels of quality evidence, respectively. Among the bioactive materials used, the most frequently analysed were: MTA, Biodentine dentin matrix hydrogel, Pro Root MTA, and EndoSequence root repair material. The highest thickness of the tertiary dentin was achieved after the use of MTA material in both imaging techniques. The remaining parameters had different results, taking into account the CBCT and micro-CT analysis. The possibilities of the qualitative and quantitative assessment of the particular parameters of tertiary dentin using CBCT and micro-CT techniques were presented and analysed. CBCT and micro-CT analyses can be useful in the assessment of tertiary dentin formed beneath the bioactive material applied during vital pulp treatment. The research argues that the presented results differ depending on the material applied to the pulp, the study duration (4-6 weeks), difference in teeth, species (rats, human), as well as the applied technique and differences in computer software used for the analysis.

OBJECTIVE: This in vitro study aimed to investigate the optical attenuation of light at 405, 660 and 780 nm sent through sound and carious human enamel and dentin, including respective individual caries zones, as well as microscopically sound-appearing tissue close to a carious lesion.
METHODS: Collimated light transmission through sections of 1000-125-µm thickness was measured and used to calculate the attenuation coefficient (AC). The data were statistically analysed with a MANOVA and Tukey\'s HSD. Precise definition of measurement points enabled separate analysis within the microstructure of lesions: the outer and inner halves of enamel (D1, D2), the translucent zone (TZ) within dentin lesions and its adjacent layers, the enamel side of the translucent zone (ESTZ) and the pulpal side of the translucent zone (PSTZ).
RESULTS: The TZ could be distinguished from its adjacent layers and from caries-free dentin at 125 µm. Sound-appearing dentin close to caries lesions significantly differed from caries-free dentin at 125 µm. While sound and carious enamel exhibited a significant difference (p < 0.05), this result was not found for D1 and D2 enamel lesions (p > 0.05). At 405 nm, no difference was found between sound and carious dentin (p > 0.05).
CONCLUSIONS: Light optical means enable the distinction between sound and carious tissue and to identify the microstructure of dentin caries partially as well as the presence of tertiary dentin formation. Information on sample thickness is indispensable when interpreting the AC.
CONCLUSIONS: Non-ionising light sources may be suitable to detect lesion progression and tertiary dentin.