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Oral Diseases Mar 2015Dentinogenesis imperfecta and dentin dysplasia are two common types of genetic oral diseases resulted from the aberrant differentiation of odontoblast. Understanding the... (Review)
Review
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.
Topics: Animals; Cell Differentiation; Dentin Dysplasia; Dentinogenesis; Gene Regulatory Networks; Humans; MicroRNAs; Odontoblasts; RNA, Messenger; Transcription Factors
PubMed: 24654877
DOI: 10.1111/odi.12237 -
Medecine Sciences : M/S Mar 2013Dentinal sensitivity is a clinical condition daily encountered by practitioners and constitutes the symptoms of dentinal hypersensitivity, a common dental pain affecting... (Review)
Review
Dentinal sensitivity is a clinical condition daily encountered by practitioners and constitutes the symptoms of dentinal hypersensitivity, a common dental pain affecting on average 30% of the population. However, the management of this pathology is not always effective due to the lack of knowledge particularly concerning the means by which dental nociceptive signals are transduced. The mechanisms underlying dentin sensitivity still remain unclear probably due to the structural and functional complexity of the players including odontoblasts, nerve endings and dentinal fluid running in the dentinal tubules. The unique spatial situation of odontoblasts, ciliated cells in close relationship with nerve terminals, suggests that they could play a pivotal role in the transduction of sensory events occurring within the dentin tissue. Our studies have identified mechano-thermosensitive transient receptor potential ion channels (TRPV1-4, TRPA8, TRPM3, KCa, TREK-1, PC1, PC2) localised on the odontoblastic membrane and at the base of the cilium. They could sense temperature variations or movements of dentinal fluid within tubules. Moreover, several voltage-gated sodium channels confer excitable properties to odontoblasts in response to injection of depolarizing currents. In vivo, these channels co-localize with nerve endings at the apical pole of odontoblasts, and their expression pattern seems to be correlated with the spatial distribution of stretch-activated KCa channels. All these data strengthen the hypothesis that odontoblasts could act as sensor cells able to transmit nociceptive signals. However, how cells sense signals and how the latter are transmitted to axons represent the main issue to be solved.
Topics: Afferent Pathways; Dental Pulp; Dentin Sensitivity; Hot Temperature; Humans; Odontoblasts; Pain Perception; Tooth
PubMed: 23544384
DOI: 10.1051/medsci/2013293016 -
Journal of Dental Research Jun 2021A comprehensive study of odontoblastic differentiation is essential to understand the process of tooth development and to achieve the ability of tooth regeneration in...
A comprehensive study of odontoblastic differentiation is essential to understand the process of tooth development and to achieve the ability of tooth regeneration in the future. Zinc finger E-box-binding homeobox 1 () is a transcription factor expressed in various neural crest-derived tissues, including the mesenchyme of the tooth germ. However, its role in odontoblastic differentiation remains unknown. In this study, we found the expression of gradually increased during odontoblast differentiation in vivo, as well as during induced differentiation of cultured primary murine dental papilla cells (mDPCs) in vitro. In addition, the differentiation of mDPCs was repressed in silenced cells. We used RNA sequencing (RNAseq) to identify the transcriptome-wide targets of and used assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) to explore the direct targets of in both the early stage (embryonic day 16.5; E16.5) and the late stage (postnatal day 0; PN0) of tooth development. We identified the motifs of transcription factors enriched in -dependent accessible chromatin regions and observed that only in the early stage of mDPCs could significantly change the accessibility of chromatin regions. In vivo and in vitro experiments confirmed that silencing of at E16.5 inhibited dentinogenesis. Analysis of RNA-seq and ATAC-seq resulted in the identification of , a gene directly regulated by during early odontoblast differentiation. enhances the expression of by binding to its -elements, and ZEB1 interacts with RUNX2. In the late stage of tooth development, we found that ZEB1 could directly bind to and increase the enhancer activity of an element upstream of and promote dentinogenesis. In this study, for the first time, we revealed that ZEB1 promoted odontoblast differentiation in the early stage by altering chromatin accessibility of -elements near genes such as , while in the late stage, it directly enhanced transcription, thereby performing a dual role.
Topics: Animals; Cell Differentiation; Extracellular Matrix Proteins; Mice; Odontoblasts; Odontogenesis; Phosphoproteins
PubMed: 33419386
DOI: 10.1177/0022034520982249 -
Endodontics & Dental Traumatology Jun 1998The response of the dental pulp to calcium hydroxide has been well described but the process of pulpal repair leading to dentinal bridge formation appears complex and... (Review)
Review
The response of the dental pulp to calcium hydroxide has been well described but the process of pulpal repair leading to dentinal bridge formation appears complex and the mechanisms remain incompletely understood. Through the precise regulation of the free calcium ion in the cytosol, cells have been able to utilize anions such as phosphates for a wide range of activities such as energy production (oxidative phosphorylation). As anions are abundant in the cytosol, intracellular levels of calcium ions are kept low, several orders of magnitude less than that of the surrounding extracellular matrix. Consequently, cells are able to use calcium ions for the regulation of many cellular events. The binding of extracellular molecules such as cytokines, hormones or antibodies, with receptors on the plasma membrane may result in short- or long-term modifications to cellular metabolism, including the mechanisms of intracellular calcium homeostasis. Cell survival depends upon the ability to adapt to changes in the cell's micro-environment. Adaptation in turn results in altered cellular activity that may be interpreted as showing that the cell has become more or less specialised. In some instances this may include the resumption of mitotic activity. If the rate or magnitude of change exceeds a cell's adaptive capacity, the cell dies. Responses of cells to alterations in their environment are reviewed as they may provide an explanation for the success of calcium hydroxide in facilitating pulpal repair and the differentiation of odontoblasts.
Topics: Calcium Hydroxide; Calcium Signaling; Cell Differentiation; Dental Pulp; Dental Pulp Capping; Dentin, Secondary; Dentinogenesis; Extracellular Matrix; Humans; Odontoblasts
PubMed: 9863418
DOI: 10.1111/j.1600-9657.1998.tb00821.x -
Bone Sep 2021Primary cilium is a protruding cellular organelle that has various physiological functions, especially in sensory reception. While an avalanche of reports on primary...
Primary cilium is a protruding cellular organelle that has various physiological functions, especially in sensory reception. While an avalanche of reports on primary cilia have been published, the function of primary cilia in dental cells remains to be investigated. In this study, we focused on the function of primary cilia in dentin-producing odontoblasts. Odontoblasts, like most other cell types, possess primary cilia, which disappear upon the knockdown of intraflagellar transport protein 88. In cilia-depleted cells, the expression of dentin sialoprotein, an odontoblastic marker, was elevated, while the deposition of minerals was slowed. This was recapitulated by the activation of canonical Wnt pathway, also decreased the ratio of ciliated cells. In dental pulp cells, as they differentiated into odontoblasts, the ratio of ciliated cells was increased, whereas the canonical Wnt signaling activity was repressed. Our results collectively underscore the roles of primary cilia in regulating odontoblastic differentiation through canonical Wnt signaling. This study implies the existence of a feedback loop between primary cilia and the canonical Wnt pathway.
Topics: Cell Differentiation; Cilia; Dental Pulp; Odontoblasts; Wnt Signaling Pathway
PubMed: 33975031
DOI: 10.1016/j.bone.2021.116001 -
Science China. Life Sciences Sep 2015The interaction between Hertwig's epithelial root sheath (HERS) and the adjacent mesenchyme is vitally important in mouse tooth root development. We previously generated...
The interaction between Hertwig's epithelial root sheath (HERS) and the adjacent mesenchyme is vitally important in mouse tooth root development. We previously generated odontoblast-specific Ctnnb1 (encoding β-catenin) deletion mice, and demonstrated that odontoblast β-catenin signaling regulates odontoblast proliferation and differentiation. However, the role of odontoblast β-catenin signaling in regulation of HERS behavior has not been fully investigated. Here, using the same odontoblast- specific Ctnnb1 deletion mice, we found that ablation of β-catenin signaling in odontoblasts led to aberrant HERS formation. Mechanistically, odontoblast-specific Ctnnb1 deletion resulted in elevated bone morphogenetic protein 7 (Bmp7) expression and reduced expression of noggin and follistatin, both of which encode extracellular inhibitors of BMPs. Furthermore, the levels of phosphorylated Smad1/5/8 were increased in HERS cells. In vitro tissue culture confirmed that BMP7 treatment disrupted the HERS structure. Taken together, we demonstrated that odontoblast β-catenin signaling may act through regulation of BMP signaling to maintain the integrity of HERS cells.
Topics: Animals; Bone Morphogenetic Protein 7; Carrier Proteins; Cell Differentiation; Cell Proliferation; Enamel Organ; Epithelial-Mesenchymal Transition; Follistatin; Gene Deletion; Gene Expression Regulation; Genotype; In Situ Hybridization; Mesoderm; Mice; Odontoblasts; Phosphorylation; Signal Transduction; Smad Proteins; Tooth Root; Up-Regulation; beta Catenin
PubMed: 26208822
DOI: 10.1007/s11427-015-4882-8 -
Differentiation; Research in Biological... 1982Numerous studies using amphibians have demonstrated that preodontoblasts emerging from the dental papilla are derived from cranial neural crest cells [4, 12, 46, 64].... (Review)
Review
Numerous studies using amphibians have demonstrated that preodontoblasts emerging from the dental papilla are derived from cranial neural crest cells [4, 12, 46, 64]. However this has not been established for mammals. The history of odonotogenesis begins during the early stages of cranial-facial development when the maxillary and mandibular processes processes develop. Continuous epithelio-mesenchymal interactions condition the histogenesis and morphogenesis of the teeth [24-26, 43, 44, 49, 51, 58] as well as the terminal differentiation of odontoblasts and ameloblasts [23, 47, 52, 54, 59, 61, 67]. During recent years a considerable amount of experimental data relating to differentiation of odontoblasts has been published. We summarize these data and attempt to integrate them in deductive hypothesis concerning the control of odontoblast differentiation.
Topics: Adenylyl Cyclases; Animals; Basement Membrane; Cell Cycle; Cell Differentiation; Epithelium; Female; Kinetics; Mice; Models, Biological; Odontoblasts; Odontogenesis; Pregnancy
PubMed: 7040152
DOI: 10.1111/j.1432-0436.1982.tb01187.x -
Connective Tissue Research 2003The terminal differentiation of odontoblasts is controlled by the inner dental epithelium (IDE) and occurs according to a tooth-specific pattern. It requires... (Review)
Review
The terminal differentiation of odontoblasts is controlled by the inner dental epithelium (IDE) and occurs according to a tooth-specific pattern. It requires temporospatially regulated epigenetic signaling and the expression of specific competence. The patterning of cusp formation was compared with that of odontoblast differentiation in the first lower molar in mice. Histology, immunostaining, and three dimensional reconstructions were completed by experimental approaches in vitro. The mesenchyme controls the pattern of cusp formation. During the cap-bell transition in the molar, a subpopulation of nondividing IDE cells from the enamel knot (EK) undergo a tooth-specific segregation in as many subpopulations as cusps will form. Epithelial cell-basement membrane interactions seem to be involved in the segregation of EK cells. The timing and spatial pattern of the segregation of EK cells correlate with cusps formation. However, the temporal pattern of odontoblast terminal differentiation is different. This discrepancy might result from cusp-specific differences either in the timing of the initiation of odontoblast terminal differentiation and/or in cell proliferation kinetics.
Topics: Animals; Animals, Newborn; Calcification, Physiologic; Cell Differentiation; Mice; Mice, Inbred CBA; Morphogenesis; Odontoblasts; Odontogenesis; Tooth Germ
PubMed: 12952192
DOI: No ID Found -
Acta Odontologica Scandinavica Apr 2020Odontoblasts 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...
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. Gene activity and protein production was determined by quantitative real-time RT-PCR and ELISA, respectively. Cellular expression of CRAMP was determined by immunocytochemistry. 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. 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.
Topics: Antimicrobial Cationic Peptides; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Humans; Immunohistochemistry; Interleukin-6; Lipopolysaccharides; Matrix Metalloproteinase 8; Odontoblasts; Real-Time Polymerase Chain Reaction; Teichoic Acids; Cathelicidins
PubMed: 31726911
DOI: 10.1080/00016357.2019.1685679 -
European Review For Medical and... Mar 2016Laser therapy is known to stimulate cell proliferation and differentiation, an effect called "biostimulation". Although many clinical applications of laser therapy take...
OBJECTIVE
Laser therapy is known to stimulate cell proliferation and differentiation, an effect called "biostimulation". Although many clinical applications of laser therapy take advantage from such positive effect, the underlying molecular mechanisms are not fully understood. The aim of this work was to investigate the effect of near-infrared laser stimulation on rat pre-odontoblast cells (MDPC-23 cells) and the molecular mechanism/s involved.
MATERIALS AND METHODS
MDPC-23 cells were stimulated with a near-infrared (980 nm) laser source with different energy settings (1-50 J, corresponding to 0.65-32.47 J/cm2) and cell proliferation was evaluated by manual count. ERK 1/2 pathway activation was evaluated by Western blot analysis.
RESULTS
1-10 J stimulation (corresponding to 0.65-6.5 J/cm2) significantly increase MDPC-23 cell proliferation and such effect seems to be mediated by ERK 1/2 signalling pathway activation, showing a key role of ERK 1/2 pathway in mediating the proliferative response induced by laser stimulation.
CONCLUSIONS
Near infrared laser stimulation with low energies (1-10 J) is able to increase cell proliferation through ERK 1/2 signalling pathway activation. At the same time, higher energy stimulation (25-50 J) induces an initial toxic effect, probably activating pro-apoptotic signalling molecules, downstream ERK 1/2 kinase. Such results foster the application of this therapeutic approach in different clinical settings in which a regenerative tissue response is needed.
Topics: Animals; Cell Differentiation; Cell Line; Cell Proliferation; Low-Level Light Therapy; MAP Kinase Signaling System; Odontoblasts; Rats
PubMed: 27010131
DOI: No ID Found