Post-mortem Interval estimate based on dental pulp: A histomorphology approach.

Estimating the post-mortem interval (PMI) of human remains based on the histomorphology of dental pulp parameters is promising, but available evidence is scarce and sometimes contradictory without a scientific model. The aim of the study is to characterise the histomorphological changes of dental pulp associated with the decomposition of human remains by a qualitative and quantitative approach. The main aim is to establish a correlation based on post-mortem (PM) dental pulp histomorphology and the PMI, and whether pulp degradation could be an available medico-legal tool for PMI estimation beyond the first week after death (late PMI). The eligible sample consisted of 27 sound teeth from 16 healthy patients aged 16 to 72 years due to orthodontic or oral surgery treatment, to create PMI's simulating the death of the subject as the time elapsed from tooth avulsion. Data collected from patients (sex, date of birth, tooth position, date and hour of the avulsion, date and hour of pulp extraction) were anonymised in accordance with the requirements of Faculty of Dental Medicine of the University of Lisbon. The sample was divided into 9 groups of 3 teeth according to different PMI sets from T0 (baseline) up to 2 weeks (T0, 7, 12, 24, 36, 48, and 72 hours, 1 and 2 weeks). All the dental samples were stored at room temperature up to the time of pulp extraction and then prepared with haematoxylin and eosin stain. High-resolution microscopy was performed to obtain histological images. An operator performed the qualitative evaluation of blood vessels, collagen fibres, and the extra-cellular matrix (ECM) in PM pulps and measured the variation in cells/nuclei density by counting 6 different ROIs (Regions of Interest) for each pulp manually and automatically (quantitative analysis). Qualitative results showed that the degeneration of dental pulp appears 7 hours after death but histological changes in vessels, fibres, and ECM in PM dental pulp are characterised by high variability, consequently it is not possible to generalise the results for early PMIs. Quantitative measurements proved that cell count cannot be standardised due to the presence of superimposed layers of cells and nuclei fragmentation. Odontoblasts did not demonstrate evidence of cellular or nuclear lysis up to 14 PM suggesting their applicability in late PMIs. Future research will focus on late PMIs and different techniques of tooth preparation.

A Review of Dentinogenesis Imperfecta and Primary Dentin Disorders in Dogs.

This review describes the clinical, radiographic and histologic characteristics of dentinogenesis imperfecta diagnosed in two unrelated young dogs without evidence of concurrent osteogenesis imperfecta. The dentition was noted to have generalized coronal discoloration ranging from grey-blue to golden brown. Clinical pulp exposure, coronal wear and fractures were observed as was radiographic evidence of endodontic disease, thin dentin walls or dystrophic obliteration of the pulp canal. The enamel was severely affected by attrition and abrasion despite histologically normal areas; loss was most likely due to poor adherence or support by the underlying abnormal dentin. Histologically, permanent and deciduous teeth examined showed thin, amorphous dentin without organized dentin tubules and odontoblasts had dysplastic cell morphology. Primary dentin disorders, including dentinogenesis imperfecta and dentin dysplasia, have been extensively studied and genetically characterized in humans but infrequently reported in dogs. Treatment in human patients is aimed at early recognition and multi-disciplinary intervention to restore and maintain normal occlusion, aesthetics, mastication and speech. Treatment in both humans and canine patients is discussed as is the documented genetic heritability of primary dentin disorders in humans.

Notoginsenoside R1 alleviates TEGDMA-induced mitochondrial apoptosis in preodontoblasts through activation of Akt/Nrf2 pathway-dependent mitophagy.

Incomplete polymerization or biodegradation of dental resin materials results in the release of resin monomers such as triethylene glycol dimethacrylate (TEGDMA), causing severe injury of dental pulp cells. To date, there has been no efficient treatment option for this complication, in part due to the lack of understanding of the mechanism underlying these phenomena. Here, for the first time, we found that notoginsenoside R1 (NR1), a bioactive ingredient extracted from Panax notoginseng, exerted an obvious protective effect on TEGDMA-induced mitochondrial apoptosis in the preodontoblast mDPC6T cell line. In terms of the mechanism of action, NR1 enhanced the level of phosphorylated Akt (protein kinase B), resulting in the activation of a transcriptional factor, nuclear factor erythroid 2-related factor 2 (Nrf2), and eventually upregulating cellular ability to resist TEGDMA-related toxicity. Inhibiting the Akt/Nrf2 pathway by pharmaceutical inhibitors significantly decreased NR1-mediated cellular antioxidant properties and aggravated mitochondrial oxidative damage in TEGDMA-treated cells. Interestingly, NR1 also promoted mitophagy, which was identified as the potential downstream of the Akt/Nrf2 pathway. Blocking the Akt/Nrf2 pathway inhibited mitophagy and abolished the protection of NR1 on cells exposed to TEGDMA. In conclusion, these findings reveal that the activation of Akt/Nrf2 pathway-mediated mitophagy by NR1 might be a promising approach for preventing resin monomer-induced dental pulp injury.

Odontoblast-like MDPC-23 cells produce pro-inflammatory IL-6 in response to lipoteichoic acid and express the antimicrobial peptide CRAMP.

Objective: Odontoblasts are thought to be involved in innate immunity but their precise role in this process is not fully understood. Here, we assess effects of lipopolysaccharide (LPS) and lipoteichoic acid (LTA), produced by Gram-negative and Gram-positive bacteria, respectively, on matrix metalloproteinase-8 (MMP-8), interleukin-6 (IL-6) and cathelin-related antimicrobial peptide (CRAMP) expression in odontoblast-like MDPC-23 cells.Material and methods: Gene activity and protein production was determined by quantitative real-time RT-PCR and ELISA, respectively. Cellular expression of CRAMP was determined by immunocytochemistry.Results: Stimulation with LTA (5 and 25 µg/ml) but not LPS (1 and 5 µg/ml) for 24 h enhanced IL-6 mRNA expression. The LTA-induced up-regulation of IL-6 mRNA levels was associated with increased IL-6 protein levels. Stimulation with either LPS or LTA for 24 h lacked effect on both MMP-8 transcript and protein expression. Immunocytochemistry disclosed that MDPC-23 cells expressed immunoreactivity for CRAMP. MDPC-23 cells showed mRNA expression for CRAMP, but stimulation with either LPS or LTA did not modulate CRAMP transcript expression.Conclusions: We show that MDPC-23 cells possess immune-like cell properties such as LTA-induced IL-6 production and expression of the antimicrobial peptide CRAMP, suggesting that odontoblasts may modulate innate immunity via these mechanisms.

Spontaneous Development of Dental Dysplasia in Aged Parp-1 Knockout Mice.

Poly(ADP-ribose) polymerase (Parp)-1 catalyzes polyADP-ribosylation using NAD+ and is involved in the DNA damage response, genome stability, and transcription. In this study, we demonstrated that aged Parp-1-/- mouse incisors showed more frequent dental dysplasia in both ICR/129Sv mixed background and C57BL/6 strain compared to aged Parp-1+/+ incisors, suggesting that Parp-1 deficiency could be involved in development of dental dysplasia at an advanced age. Computed tomography images confirmed that dental dysplasia was observed at significantly higher incidences in Parp-1-/- mice. The relative calcification levels of Parp-1-/- incisors were higher in both enamel and dentin (p < 0.05). Immunohistochemical analysis revealed (1) Parp-1 positivity in ameloblasts and odontoblasts in Parp-1+/+ incisor, (2) weaker dentin sialoprotein positivity in dentin of Parp-1-/- incisor, and (3) bone sialoprotein positivity in dentin of Parp-1-/- incisor, suggesting ectopic osteogenic formation in dentin of Parp-1-/- incisor. These results indicate that Parp-1 deficiency promotes odontogenic failure in incisors at an advanced age. Parp-1 deficiency did not affect dentinogenesis during the development of mice, suggesting that Parp-1 is not essential in dentinogenesis during development but is possibly involved in the regulation of continuous dentinogenesis in the incisors at an advanced age.

Changes in the Periodontium and Pulp in ISIAH Rats Caused by Stress Exposures in Different Modes.

It was shown that the intensity of morphological changes in the dental system tissues (periodontium and pulp) of ISIAH rats depends on the mode of stress exposure. Acute stress was associated with a significant increase in the area of periodontal and pulp vessels, a decrease in the area of connective tissue of these components, and an increase in the thickness of the vascular endothelium. Chronic stress in these animals induced an increase in the thickness of the endothelial layer of the periodontal and pulp vessels, fibromatosis (increase in the number of fibroblasts), and a sharp decrease in the level of odontoblasts.

Detection of bone marrow-derived fibrocytes in human dental pulp repair.

AIM: To explore the expression profile of CD45+/pro-collagen I+ fibrocytes in intact dental pulps as well as during wound healing in adult dental pulp tissue. METHODOLOGY: A total of 16 healthy permanent teeth were obtained from young patients (18 to 25 years) undergoing orthodontic treatment. Routine pulp capping with mineral trioxide aggregate (MTA) was performed under local anaesthesia to induce a mineralized barrier at the exposed surface. Teeth were extracted from patients after 7, 14 and 35 days. Sections of the extracted teeth were prepared and stained for various markers using indirect immunofluorescence. Fibrocytes were counted, and the data were statistically evaluated using the Dunnett test. RESULTS: In uninflammed pulp tissue, a pro-collagen I-positive reaction was detected in odontoblasts, as well as in perivascular cells. Most of the CD45-positive cells were negative for pro-collagen I in normal pulp tissue, whereas CD45+/pro-collagen I+ fibrocytes were detected 7 days after injury. At day 14, fibrocytes were recognized under the fibrous matrix in contact with MTA and had infiltrated into regions of new capillary formation, where the fibrocytes were positively stained for vascular endothelial growth factor. By 35 days, fibrocytes were few, coincident with the formation of dentine bridges. The number of fibrocytes peaked 7 days post-injury and decreased at 14 days. CONCLUSIONS: The presence of fibrocytes in human pulp wound healing was observed. The spatiotemporal distribution of fibrocytes suggests that fibrocytes are involved in the early stages of pulp wound healing, specifically by contributing to new blood vessel formation.

Zebrafish sp7 mutants show tooth cycling independent of attachment, eruption and poor differentiation of teeth.

The capacity to fully replace teeth continuously makes zebrafish an attractive model to explore regeneration and tooth development. The requirement of attachment bone for the appearance of replacement teeth has been hypothesized but not yet investigated. The transcription factor sp7 (osterix) is known in mammals to play an important role during odontoblast differentiation and root formation. Here we study tooth replacement in the absence of attachment bone using sp7 zebrafish mutants. We analysed the pattern of tooth replacement at different stages of development and demonstrated that in zebrafish lacking sp7, attachment bone is never present, independent of the stage of tooth development or fish age, yet replacement is not interrupted. Without bone of attachment we observed abnormal orientation of teeth, and abnormal connection of pulp cavities of predecessor and replacement teeth. Mutants lacking sp7 show arrested dentinogenesis, with non-polarization of odontoblasts and only a thin layer of dentin deposited. Osteoclast activity was observed in sp7 mutants; due to the lack of bone of attachment, remodelling was diminished but nevertheless present along the pharyngeal bone. We conclude that tooth replacement is ongoing in the sp7 mutant despite poor differentiation and defective attachment. Without bone of attachment tooth orientation and pulp organization are compromised.

Pro-Inflammatory Cytokine TNF-α Attenuates BMP9-Induced Osteo/ Odontoblastic Differentiation of the Stem Cells of Dental Apical Papilla (SCAPs).

BACKGROUND/AIMS: Periapical periodontitis is a common oral disease caused by bacterial invasion of the tooth pulp, which usually leads to local release of pro-inflammatory cytokines and osteolytic lesion. This study is intended to examine the effect of TNF-α on BMP9-induced osteogenic differentiation of the stem cells of dental apical papilla (SCAPs). METHODS: Rat model of periapical periodontitis was established. TNF-α expression was assessed. Osteogenic markers and ectopic bone formation in iSCAPs were analyzed upon BMP9 and TNF-α treatment. RESULTS: Periapical periodontitis was successfully established in rat immature permanent teeth with periapical lesions, in which TNF-α was shown to release during the inflammatory phase. BMP9-induced alkaline phosphatase activity, the expression of osteocalcin and osteopontin, and matrix mineralization in iSCAPs were inhibited by TNF-α in a dose-dependent fashion, although increased AdBMP9 partially overcame TNF-α inhibition. Furthermore, high concentration of TNF-α effectively inhibited BMP9-induced ectopic bone formation in vivo. CONCLUSION: TNF-α plays an important role in periapical bone defect during the inflammatory phase and inhibits BMP9-induced osteoblastic differentiation of iSCAPs, which can be partially reversed by high levels of BMP9. Therefore, BMP9 may be further explored as a potent osteogenic factor to improve osteo/odontogenic differentiation in tooth regeneration in chronic inflammation conditions.

Biodentine Reduces Tumor Necrosis Factor Alpha-induced TRPA1 Expression in Odontoblastlike Cells.

INTRODUCTION: The transient receptor potential (TRP) ion channels have emerged as important cellular sensors in both neuronal and non-neuronal cells, with TRPA1 playing a central role in nociception and neurogenic inflammation. The functionality of TRP channels has been shown to be modulated by inflammatory cytokines. The aim of this study was to investigate the effect of inflammation on odontoblast TRPA1 expression and to determine the effect of Biodentine (Septodent, Paris, France) on inflammatory-induced TRPA1 expression. METHODS: Immunohistochemistry was used to study TRPA1 expression in pulp tissue from healthy and carious human teeth. Pulp cells were differentiated to odontoblastlike cells in the presence of 2 mmol/L beta-glycerophosphate, and these cells were used in quantitative polymerase chain reaction, Western blotting, calcium imaging, and patch clamp studies. RESULTS: Immunofluorescent staining revealed TRPA1 expression in odontoblast cell bodies and odontoblast processes, which was more intense in carious versus healthy teeth. TRPA1 gene expression was induced in cultured odontoblastlike cells by tumor necrosis factor alpha, and this expression was significantly reduced in the presence of Biodentine. The functionality of the TRPA1 channel was shown by calcium microfluorimetry and patch clamp recording, and our results showed a significant reduction in tumor necrosis factor alpha-induced TRPA1 responses after Biodentine treatment. CONCLUSIONS: In conclusion, this study showed TRPA1 to be modulated by caries-induced inflammation and that Biodentine reduced TRPA1 expression and functional responses.

PEX6 is Expressed in Photoreceptor Cilia and Mutated in Deafblindness with Enamel Dysplasia and Microcephaly.

Deafblindness is part of several genetic disorders. We investigated a consanguineous Egyptian family with two siblings affected by congenital hearing loss and retinal degeneration, initially diagnosed as Usher syndrome type 1. At teenage, severe enamel dysplasia, developmental delay, and microcephaly became apparent. Genome-wide homozygosity mapping and whole-exome sequencing detected a homozygous missense mutation, c.1238G>T (p.Gly413Val), affecting a highly conserved residue of peroxisomal biogenesis factor 6, PEX6. Biochemical profiling of the siblings revealed abnormal and borderline plasma phytanic acid concentration, and cerebral imaging revealed white matter disease in both. We show that Pex6 localizes to the apical extensions of secretory ameloblasts and differentiated odontoblasts at early stages of dentin synthesis in mice, and to cilia of retinal photoreceptor cells. We propose PEX6, and possibly other peroxisomal genes, as candidate for the rare cooccurrence of deafblindness and enamel dysplasia. Our study for the first time links peroxisome biogenesis disorders to retinal ciliopathies.

Dental Pulp Defence and Repair Mechanisms in Dental Caries.

Dental caries is a chronic infectious disease resulting from the penetration of oral bacteria into the enamel and dentin. Microorganisms subsequently trigger inflammatory responses in the dental pulp. These events can lead to pulp healing if the infection is not too severe following the removal of diseased enamel and dentin tissues and clinical restoration of the tooth. However, chronic inflammation often persists in the pulp despite treatment, inducing permanent loss of normal tissue and reducing innate repair capacities. For complete tooth healing the formation of a reactionary/reparative dentin barrier to distance and protect the pulp from infectious agents and restorative materials is required. Clinical and in vitro experimental data clearly indicate that dentin barrier formation only occurs when pulp inflammation and infection are minimised, thus enabling reestablishment of tissue homeostasis and health. Therefore, promoting the resolution of pulp inflammation may provide a valuable therapeutic opportunity to ensure the sustainability of dental treatments. This paper focusses on key cellular and molecular mechanisms involved in pulp responses to bacteria and in the pulpal transition between caries-induced inflammation and dentinogenic-based repair. We report, using selected examples, different strategies potentially used by odontoblasts and specialized immune cells to combat dentin-invading bacteria in vivo.

The physiologic sclerotic dentin: A literature-based hypothesis.

Despite the many hypotheses trying to explain how the physiologic sclerotic dentin is formed, there has been so far no convincing explanation for all of its observations. In this review, we tried to make a hypothesis based on the facts published to date. We found that the apoptosis of odontoblasts, which takes place after the formation of the apical constriction, may be the key-factor for the development of physiologic sclerotic dentin, because the resulting apoptotic bodies cannot be eliminated through phagocytosis and become trapped within the dentinal tubules due to the continuous formation of secondary dentin. The apoptotic bodies suffer later from a secondary or apoptotic necrosis leading to the release of the internal contents of pyrophosphate and hydrogen phosphate. Pyrophosphate can dehydrate the dentin and hydrogen phosphate can demineralize it, leading to the release of Ca(2+) ions which then contribute to the intratubular mineralization.

Disruption of Smad4 in odontoblasts and dental epithelial cells influences the phenotype of multiple keratocystic odontogenic tumors.

Keratocystic odontogenic tumors (KCOTs) are cystic epithelial neoplasms with a high recurrence rate. The molecular mechanisms underlying the initiation and progression of KCOTs are still largely unknown. Previous research showed that specific ablation of Smad4 in odontoblasts and dental epithelia resulted in spontaneous KCOTs in mice, and that constitutively activated Hedgehog (Hh) signaling was detected in the cyst epithelia of both Smad4(Co/Co) OC-Cre and Smad4(Co/Co) K5-Cre mice. Here, we ablated Smad4 in mouse odontoblasts and dental epithelia and compared the sizes and numbers of KCOTs. Both the number and size of KCOTs in Smad4(Co/Co) OC-Cre mice were larger than those in Smad4(Co/Co) K5-Cre mice, suggesting that paracrine signals from root odontoblasts play a more important role than those from Hertwig's epithelial root sheath (HERS) cells.

Histological Evaluation of Allium sativum Oil as a New Medicament for Pulp Treatment of Permanent Teeth.

OBJECTIVE: The objective of this study was to evaluate the histo pathology effects of two medicaments Allium sativum oil and formocresol on the remaining pulp tissue of the permanent teething children. MATERIALS AND METHODS: A total of 18 premolars were included in this study. Two sound premolars were extracted and subjected to histological examination to show the normal pulp tissue. Pulpo tomy procedure was performed in the rest of the remaining 16 premolars; half of them using Allium sativum oil and the rest of the tested premolars were medicated using formocresol and all were sealed with suitable restoration. Then, premolars extracted at variable intervals (48 hours, 2 weeks, 1 month, 2 months), stained using hemotoxylin and eosin etain (H&E) and prepared for histopathology examination. RESULTS: Histological evaluation seemed far more promising for Allium sativum oil than formocresol. Histological evaluation revealed that teeth treated with Allium sativa oil showed infammatory changes that had been resolved in the end of the study. On the contrary, the severe chronic infammation of pulp tissue accompanied with formocresol eventually produced pulp necrosis with or without fibrosis. In addition, pulp calcification was evidenced in certain cases. CONCLUSION: Allium sativum oil is a biocompatible material that is compatible with vital human pulp tissue. It offers a good healing potential, leaving the remaining pulp tissue healthy and functioning.

Disruption of Tgfbr2 in odontoblasts leads to aberrant pulp calcification.

Transforming growth factor ß (TGF-ß) signaling has been implicated in dentin formation and repair; however, the molecular mechanisms underlying dentin formation remain unclear. To address the role of TGF-ß signaling in dentin formation, we analyzed odontoblast-specific Tgfbr2 conditional knockout mice. The mutant mice had aberrant teeth with thin dysplastic dentin and pulpal obliteration, similar to teeth from human patients with dentinogenesis imperfecta type II and dentin dysplasia. In mutant, the odontoblasts lost their cellular polarity, and matrix secretion was disrupted after mantle dentin formation. As a consequence, the amount of predentin decreased significantly, and an ectopic fibrous matrix was formed below the odontoblast layer. This matrix gradually calcified and obliterated the pulp chamber with increasing age. Immunohistochemistry revealed decreased expression of alkaline phosphatase in mutant odontoblasts. In mutant dentin, Dsp expression was reduced, but Dmp1 expression increased significantly. Collagen type I, biglycan, and Dsp were expressed in the ectopic matrix. These results suggest that loss of responsiveness to TGF-ß in odontoblasts results in impaired matrix formation and pulpal obliteration. Our study indicates that TGF-ß signaling plays an important role in dentin formation and pulp protection. Furthermore, our findings may provide new insight into possible mechanisms underlying human hereditary dentin disorders and reparative dentin formation.

Microtubule-associated protein tau (Mapt) is expressed in terminally differentiated odontoblasts and severely down-regulated in morphologically disturbed odontoblasts of Runx2 transgenic mice.

Runx2 is an essential transcription factor for osteoblast and odontoblast differentiation and the terminal differentiation of chondrocytes. We have previously shown that the terminal differentiation of odontoblasts is inhibited in Runx2 transgenic {Tg(Col1a1-Runx2)} mice under the control of the 2.3-kb Col1a1 promoter, which directs the transgene expression to osteoblasts and odontoblasts. Odontoblasts show severe reductions in Dspp and nestin expression and lose their characteristic polarized morphology, including a long process extending to dentin, in Tg(Col1a1-Runx2) mice. We study the molecular mechanism of odontoblast morphogenesis by comparing gene expression in the molars of wild-type and Tg(Col1a1-Runx2) mice, focusing on cytoskeleton-related genes. Using microarray, we found that the gene expression of microtubule-associated protein tau (Mapt), a neuronal phosphoprotein with important roles in neuronal biology and microtubule dynamics and assembly, was high in wild-type molars but severely reduced in Tg(Col1a1-Runx2) molars. Immunohistochemical analysis revealed that Mapt was specifically expressed in terminally differentiated odontoblasts including their processes in wild-type molars but its expression was barely detectable in Tg(Col1a1-Runx2) molars. Double-staining of Mapt and Runx2 showed their reciprocal expression in odontoblasts. Mapt and tubulin co-localized in odontoblasts in wild-type molars. Immunoelectron microscopic analysis demonstrated Mapt lying around α-tubulin-positive filamentous structures in odontoblast processes. Thus, Mapt is a useful marker for terminally differentiated odontoblasts and might play an important role in odontoblast morphogenesis.

Abnormal differentiation of dental pulp cells in cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is a skeletal dysplasia caused by heterozygous mutations of RUNX2, a gene that is essential for the mineralization of bone and tooth. We isolated primary dental pulp cells from a 10-y-old patient and tested their proliferative capacity, alkaline phosphatase activity, and ability to form mineralized nodules, in comparison with those from 7 healthy children. All these measures were reduced in primary dental pulp cells from the CCD patient. The expression of the osteoblast/odontoblast-associated genes RUNX2, ALP, OCN, and DSPP was also found to be significantly decreased in the primary dental pulp cells of the CCD patient. The osteoclast-related markers TRAP, CTSK, CTR, and MMP9 were decreased in primary dental pulp cells cocultured with human peripheral blood mononuclear cells. Moreover, the expression of RANKL and the ratio of RANKL/OPG were both reduced in the cells from the CCD patient, indicating that the RUNX2 mutation interfered with the bone-remodeling pathway and decreased the capacity of primary dental pulp cells to support osteoclast differentiation. These effects may be partly responsible for the defects in tooth development and the retention of primary teeth that is typical of CCD.

The fine tuning role of microRNA-RNA interaction in odontoblast differentiation and disease.

Dentinogenesis imperfecta and dentin dysplasia are two common types of genetic oral diseases resulted from the aberrant differentiation of odontoblast. Understanding the mechanisms of odontoblast differentiation is crucial for finding the diagnosis candidate genes and treatment targets for such kinds of diseases. Previous work has identified a battery of transcription factors and growth factors regulating odontoblast differentiation; however, the post-transcriptional regulating mechanisms of them are poorly studied. MicroRNAs (miRNA) are a group of non-coding RNAs widely studied in organ development, inflammation, and tumorigenesis because of its inhibitory effects on the target mRNAs. Also, miRNAs along with their binding targets form a complex competing endogenous RNA (ceRNA) network where miRNAs serve as the fine tuning balancers between their targets. Recent reports demonstrated the essential role of the miRNA pathway in dentinogenesis and the regulatory role of several specific miRNAs in the in vitro model of odontoblast differentiation. Herein, we will discuss the general roles of miRNA in diseases, the function of miRNAs during odontoblast differentiation, and finally the potential pathological mechanisms through which miRNAs cause the odontoblast-related diseases.

Investigation of functional activity human dental pulp stem cells at acute and chronic pulpitis.

UNLABELLED: It is already recognized that together with the other connective tissues organ-specific progenic stem cells are also found in postnatal dental pulp. This group of undifferentiated cells is only 1% of total cell population of the pulp. The aim of the study was the identification of stem cells in human dental pulp, detection of their localization and assessment of functional activity during inflammation process and/or at norm. The obtained results showed that at acute pulpitis the pulp stroma is hypocellular in comparison with the norm but cells proliferative activity is low. CD 133 and NCAM (CD 56) positive stem cells were found in perivascularl space of the pulp stroma and in Hohle layer. At process prolongation and transition to the chronic phase pulp stroma is hypercellular, the cells with large, rounded or oval-shaped nuclei with clear chromatin appear together with fibroblasts. They are distributed as about entire thickness of the stroma as especially Hohle layer. In such cells higher proliferative activity (Ki67 expression) was observed. The cells in the mentioned proliferation phase are intensively marked by CD133, the rate of which is high in Hohle layer and along it. A large number of NCAM (CD 56) positive cells appear in pulp stroma. CONCLUSIONS: During pulpitis an involvement of stem cells into the process of reparative dentinogenesis should be conducted stepwise. In acute cases of the disease, stem cell perivascularl mobilization and proliferation and its migration to Hohle layer occur in response to irritation /stimulation. Chronification of the process leads not only to the migration of stem cells to the periphery of the pulp but also s their В«maturationВ¼ (increase of NCAM expression in the stem cells), which causes an increase the number of dentin producing active odontoblasts and initiation of reparative dentinogenesis.