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International Journal of Molecular... Feb 2021The macroscopic and microscopic anatomy of the oral cavity is complex and unique in the human body. Soft-tissue structures are in close interaction with mineralized... (Review)
Review
The macroscopic and microscopic anatomy of the oral cavity is complex and unique in the human body. Soft-tissue structures are in close interaction with mineralized bone, but also dentine, cementum and enamel of our teeth. These are exposed to intense mechanical and chemical stress as well as to dense microbiologic colonization. Teeth are susceptible to damage, most commonly to caries, where microorganisms from the oral cavity degrade the mineralized tissues of enamel and dentine and invade the soft connective tissue at the core, the dental pulp. However, the pulp is well-equipped to sense and fend off bacteria and their products and mounts various and intricate defense mechanisms. The front rank is formed by a layer of odontoblasts, which line the pulp chamber towards the dentine. These highly specialized cells not only form mineralized tissue but exert important functions as barrier cells. They recognize pathogens early in the process, secrete antibacterial compounds and neutralize bacterial toxins, initiate the immune response and alert other key players of the host defense. As bacteria get closer to the pulp, additional cell types of the pulp, including fibroblasts, stem and immune cells, but also vascular and neuronal networks, contribute with a variety of distinct defense mechanisms, and inflammatory response mechanisms are critical for tissue homeostasis. Still, without therapeutic intervention, a deep carious lesion may lead to tissue necrosis, which allows bacteria to populate the root canal system and invade the periradicular bone via the apical foramen at the root tip. The periodontal tissues and alveolar bone react to the insult with an inflammatory response, most commonly by the formation of an apical granuloma. Healing can occur after pathogen removal, which is achieved by disinfection and obturation of the pulp space by root canal treatment. This review highlights the various mechanisms of pathogen recognition and defense of dental pulp cells and periradicular tissues, explains the different cell types involved in the immune response and discusses the mechanisms of healing and repair, pointing out the close links between inflammation and regeneration as well as between inflammation and potential malignant transformation.
Topics: Animals; Antigens, Neoplasm; Carcinogenesis; Carcinoma, Squamous Cell; Chemokines; Complement System Proteins; Dental Caries; Dental Pulp; Dentin; Fibroblasts; Humans; Intracellular Signaling Peptides and Proteins; Mesenchymal Stem Cells; Mouth Neoplasms; Nerve Net; Neuropeptides; Nitric Oxide; Odontoblasts; Periapical Granuloma; Periapical Periodontitis; Periapical Tissue; Pulpitis; Radicular Cyst
PubMed: 33540711
DOI: 10.3390/ijms22031480 -
Cells Jul 2022BMP signaling plays an important role in dentin development. BMPs and antagonists regulate odontoblast differentiation and downstream gene expression via canonical Smad... (Review)
Review
BMP signaling plays an important role in dentin development. BMPs and antagonists regulate odontoblast differentiation and downstream gene expression via canonical Smad and non-canonical Smad signaling pathways. The interaction of BMPs with their receptors leads to the formation of complexes and the transduction of signals to the canonical Smad signaling pathway (for example, BMP ligands, receptors, and Smads) and the non-canonical Smad signaling pathway (for example, MAPKs, p38, Erk, JNK, and PI3K/Akt) to regulate dental mesenchymal stem cell/progenitor proliferation and differentiation during dentin development and homeostasis. Both the canonical Smad and non-canonical Smad signaling pathways converge at transcription factors, such as Dlx3, Osx, Runx2, and others, to promote the differentiation of dental pulp mesenchymal cells into odontoblasts and downregulated gene expressions, such as those of DSPP and DMP1. Dysregulated BMP signaling causes a number of tooth disorders in humans. Mutation or knockout of BMP signaling-associated genes in mice results in dentin defects which enable a better understanding of the BMP signaling networks underlying odontoblast differentiation and dentin formation. This review summarizes the recent advances in our understanding of BMP signaling in odontoblast differentiation and dentin formation. It includes discussion of the expression of BMPs, their receptors, and the implicated downstream genes during dentinogenesis. In addition, the structures of BMPs, BMP receptors, antagonists, and dysregulation of BMP signaling pathways associated with dentin defects are described.
Topics: Animals; Bone Morphogenetic Proteins; Dentin; Humans; Mice; Odontoblasts; Phosphatidylinositol 3-Kinases; Signal Transduction
PubMed: 35883659
DOI: 10.3390/cells11142216 -
Frontiers in Bioscience (Elite Edition) Jan 2011We review firstly the specificities of the different types of dentin present in mammalian teeth. The outer layers include the mantle dentin, the Tomes' granular and the... (Review)
Review
We review firstly the specificities of the different types of dentin present in mammalian teeth. The outer layers include the mantle dentin, the Tomes' granular and the hyaline Hopewell-Smith's layers. Circumpulpal dentin forming the bulk of the tooth, comprises intertubular and peritubular dentin. In addition to physiological primary and secondary dentin formation, reactionary dentin is produced in response to pathological events. Secondly, we evaluate the role of odontoblasts in dentin formation, their implication in the synthesis and secretion of type I collagen fibrils and non-collagenous molecules. Thirdly, we study the composition and functions of dentin extracellular matrix (ECM) molecules implicated in dentinogenesis. As structural proteins they are mineralization promoters or inhibitors. They are also signaling molecules. Three different forms of dentinogenesis are identified: i) matrix vesicles are implicated in early dentin formation, ii) collagen and some proteoglycans are involved in the formation of predentin, further transformed into intertubular dentin, iii) the distal secretion of some non-collagenous ECM molecules and some serum proteins contribute to the formation of peritubular dentin.
Topics: Animals; Biological Evolution; Collagen Type I; Dentin; Extracellular Matrix; Humans; Odontoblasts; Tooth Calcification
PubMed: 21196346
DOI: 10.2741/e281 -
Cell Communication and Signaling : CCS May 2021Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from damaged mitochondria into the cytosol. mtDNA stress may contribute to cyclic GMP-AMP...
BACKGROUND
Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from damaged mitochondria into the cytosol. mtDNA stress may contribute to cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway activation in infectious diseases. Odontoblasts are the first cells challenged by cariogenic bacteria and involved in maintenance of the pulp immune and inflammatory responses to dentine-invading pathogens. In this study, we investigated that mtDNA as an important inflammatory driver participated in defending against bacterial invasion via cGAS-STING pathway in odontoblasts.
METHODS
The normal tissues, caries tissues and pulpitis tissues were measured by western blotting and immunohistochemical staining. Pulpitis model was built in vitro to evaluated the effect of the cGAS-STING pathway in odontoblast-like cell line (mDPC6T) under inflammation. Western blot and real-time PCR were performed to detect the expression of cGAS-STING pathway and pro-inflammatory cytokines. The mitochondrial function was evaluated reactive oxygen species (ROS) generated by mitochondria using MitoSOX Red dye staining. Cytosolic DNA was assessed by immunofluorescent staining and real-time PCR in mDPC6T cells after LPS stimulation. Furthermore, mDPC6T cells were treated with ethidium bromide (EtBr) to deplete mtDNA or transfected with isolated mtDNA. The expression of cGAS-STING pathway and pro-inflammatory cytokines were measured.
RESULTS
The high expression of cGAS and STING in caries and pulpitis tissues in patients, which was associated with inflammatory progression. The cGAS-STING pathway was activated in inflamed mDPC6T. STING knockdown inhibited the nuclear import of p65 and IRF3 and restricted the secretion of the inflammatory cytokines CXCL10 and IL-6 induced by LPS. LPS caused mitochondrial damage in mDPC6T, which promoted mtDNA leakage into the cytosol. Depletion of mtDNA inhibited the cGAS-STING pathway and nuclear translocation of p65 and IRF3. Moreover, repletion of mtDNA rescued the inflammatory response, which was inhibited by STING knockdown.
CONCLUSION
Our study systematically identified a novel mechanism of LPS-induced odontoblast inflammation, which involved mtDNA leakage from damaged mitochondria into the cytosol stimulating the cGAS-STING pathway and the inflammatory cytokines IL-6 and CXCL10 secretion. The mtDNA-cGAS-STING axis could be a potent therapeutic target to prevent severe bacterial inflammation in pulpitis. Video Abstract.
Topics: Cell Line; Cytosol; DNA, Mitochondrial; Dental Caries; Humans; Inflammation; Lipopolysaccharides; Membrane Proteins; Mitochondria; Nucleotidyltransferases; Odontoblasts; Pulpitis; Signal Transduction
PubMed: 34016129
DOI: 10.1186/s12964-021-00738-7 -
Australian Dental Journal Mar 2007The dental pulp is a unique tissue and its importance in the long-term prognosis of the tooth is often ignored by clinicians. It is unique in that it resides in a rigid...
The dental pulp is a unique tissue and its importance in the long-term prognosis of the tooth is often ignored by clinicians. It is unique in that it resides in a rigid chamber which provides strong mechanical support and protection from the microbial rich oral environment. If this rigid shell loses its structural integrity, the pulp is under the threat of the adverse stimuli from the mouth, such as caries, cracks, fractures and open restoration margins, all of which provide pathways for micro-organisms and their toxins to enter the pulp. The pulp initially responds to irritation by becoming inflamed and, if left untreated, this will progress to pulp necrosis and infection. The inflammation will also spread to the surrounding alveolar bone and cause periapical pathosis. The magnitude of pulp-related problems should not be underestimated since their most serious consequence is oral sepsis, which can be life threatening, and hence correct diagnosis and management are essential. Clinicians must have a thorough understanding of the physiological and pathological features of the dental pulp as well as the biological consequences of treatment interventions.
Topics: Dental Pulp; Dental Pulp Diseases; Disease Progression; Humans; Microcirculation; Odontoblasts; Pulpitis; Regional Blood Flow
PubMed: 17546858
DOI: 10.1111/j.1834-7819.2007.tb00525.x -
International Journal of Molecular... Jul 2020In vertebrates, biomineralization is a feature considered unique to mature osteoblasts and odontoblasts by which they synthesize hydroxyapatite (HAP), which is deposited...
In vertebrates, biomineralization is a feature considered unique to mature osteoblasts and odontoblasts by which they synthesize hydroxyapatite (HAP), which is deposited in the collagen matrix to construct endoskeleton. For many decades, the mechanisms that modulate differentiation and maturation of these specialized cells have been sought as a key to understanding bone-remodeling defects. Here, we report that biomineralization is an innate ability of all mammalian cells, irrespective of cell type or maturation stage. This innate biomineralization is triggered by the concomitant exposure of living cells to three indispensable elements: calcium ion, phosphoester salt, and alkaline phosphatase. Any given somatic cell, including undifferentiated mononuclear cells, can undergo a biomineralization process to produce calcium-phosphate agglomerates. The biologically generated minerals under such conditions are composed of genuine HAP crystallites of Ca(PO)(OH) and 5-10 nanometer (nm) in size. This discovery will profoundly improve our understanding of bone metabolism and ectopic calcifications.
Topics: Alkaline Phosphatase; Animals; Biomineralization; Bone and Bones; Calcium Phosphates; Cell Differentiation; Cell Line; Cell Line, Tumor; Collagen; Durapatite; HEK293 Cells; HL-60 Cells; HeLa Cells; Humans; K562 Cells; MCF-7 Cells; Mammals; Mice; NIH 3T3 Cells; Odontoblasts; Osteoblasts; PC-3 Cells; THP-1 Cells; U937 Cells
PubMed: 32650435
DOI: 10.3390/ijms21144820 -
The International Journal of... Feb 1995Reactionary dentinogenesis is the secretion of a tertiary dentine matrix by surviving odontoblast cells in response to an appropriate stimulus. Whilst this stimulus may... (Review)
Review
Reactionary dentinogenesis is the secretion of a tertiary dentine matrix by surviving odontoblast cells in response to an appropriate stimulus. Whilst this stimulus may be exogenous in nature, it may also be from endogenous tissue components released from the matrix during pathological processes. Implantation of isolated dentine extracellular matrix components in unexposed cavities of ferret teeth led to stimulation of underlying odontoblasts and a response of reactionary dentinogenesis. Affinity chromatography of the active components prior to implantation and assay for growth factors indicated that this material contained significant amounts of TGF-beta 1, a growth factor previously shown to influence odontoblast differentiation and secretory behavior. Reactionary dentinogenesis during dental caries probably results from solubilization of growth factors, TGF-beta in particular, from the dentine matrix which then are responsible for initiating the stimulatory effect on the odontoblasts. Compositional differences in tertiary dentine matrices beneath carious lesions in human teeth have also been shown indicating modulation of odontoblast secretion during reactionary and reparative dentinogenesis.
Topics: Animals; Dentinogenesis; Extracellular Matrix; Humans; Odontoblasts; Phenotype
PubMed: 7626417
DOI: No ID Found -
The International Journal of... Feb 1995Odontoblasts are post-mitotic, neural crest-derived, cells which overtly differentiate according to tooth specific temporo-spatial patterns and secrete predentin-dentin... (Review)
Review
Odontoblasts are post-mitotic, neural crest-derived, cells which overtly differentiate according to tooth specific temporo-spatial patterns and secrete predentin-dentin components. Neither the timing nor the molecular mechanisms of their specification are known and the problem of their patterning in the developing jaws is far from being solved. On the other hand, some significative strides were made concerning the control of their terminal differentiation. Fibronectin interacting with a 165 kDa, non integrin, membrane protein intervenes in the cytoskeletal reorganization involved in odontoblast polarization and their terminal differentiation can be triggered in vitro by immobilized members of the TGF beta family. Histological aspects and the transcriptional phenotypes (transcripts of TGF beta s, BMPs, msxs, IGF1, fibronectin, osteonectin, bone sialoprotein genes) are very similar in vivo and in vitro. In vivo members of the TGF beta super family secreted by preameloblasts, trapped and activated by basement membrane associated components, might initiate odontoblast terminal differentiation.
Topics: Animals; Basement Membrane; Cell Differentiation; Epithelium; Extracellular Matrix Proteins; Fibronectins; Growth Substances; Neural Crest; Odontoblasts
PubMed: 7626422
DOI: No ID Found -
Saudi Medical Journal Feb 2018Herbal remedies are used throughout the world, either in earlier or in recent times. The number of studies on this alternative therapeutic system increased in the last... (Review)
Review
Herbal remedies are used throughout the world, either in earlier or in recent times. The number of studies on this alternative therapeutic system increased in the last decades. In this paper, the relevant literature on the use of natural products in root canal therapy is revised from a MEDLINE database search. The uses of medicinal plants in endodontics include cleaning and disinfection of root canals, intracanal medicaments between appointments, sealer cements, and for removal of obturation material. Other studies showed the effect of natural products in pulpal and dentin repair. Their use is anecdotal, and their effectiveness showed to be variable and is always compared to the chemical standards currently being used. Alkaloids, coumarins, saponins, and flavonoids are aromatic substances that are produced by plants and evaluated for their therapeutic potential. Further investigation into benefits of natural products is warranted.
Topics: Biological Products; Endodontics; Humans; Odontoblasts; Root Canal Irrigants; Root Canal Therapy; Smear Layer; Solvents
PubMed: 29436559
DOI: 10.15537/smj.2018.2.21038 -
European Journal of Cell Biology Jan 2019Cell polarity identifies the asymmetry of a cell. Various types of cells, including odontoblasts and epithelial cells, polarize to fulfil their destined functions.... (Review)
Review
Cell polarity identifies the asymmetry of a cell. Various types of cells, including odontoblasts and epithelial cells, polarize to fulfil their destined functions. Odontoblast polarization is a prerequisite and fundamental step for tooth development and tubular dentin formation. Current knowledge of odontoblast polarization, however, is very limited, which greatly impedes the development of novel approaches for regenerative endodontics. Compared to odontoblasts, epithelial cell polarization has been extensively studied over the last several decades. The knowledge obtained from epithelia polarization has been found applicable to other cell types, which is particularly useful considering the remarkable similarities of the morphological and compositional features between polarized odontoblasts and epithelia. In this review, we first discuss the characteristics, the key regulatory factors, and the process of epithelial polarity. Next, we compare the known facts of odontoblast polarization with epithelial cells. Lastly, we clarify knowledge gaps in odontoblast polarization and propose the directions for future research to fill the gaps, leading to the advancement of regenerative endodontics.
Topics: Animals; Cell Polarity; Epithelial Cells; Models, Biological; Odontoblasts; rho GTP-Binding Proteins
PubMed: 30473389
DOI: 10.1016/j.ejcb.2018.11.003