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European Cells & Materials Jul 2021Dentineogenesis starts on odontoblasts, which synthesise and secrete non-collagenous proteins (NCPs) and collagen. When dentine is injured, dental pulp... (Review)
Review
Dentineogenesis starts on odontoblasts, which synthesise and secrete non-collagenous proteins (NCPs) and collagen. When dentine is injured, dental pulp progenitors/mesenchymal stem cells (MSCs) can migrate to the injured area, differentiate into odontoblasts and facilitate formation of reactionary dentine. Dental pulp progenitor cell/MSC differentiation is controlled at given niches. Among dental NCPs, dentine sialophosphoprotein (DSPP) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family, whose members share common biochemical characteristics such as an Arg-Gly-Asp (RGD) motif. DSPP expression is cell- and tissue-specific and highly seen in odontoblasts and dentine. DSPP mutations cause hereditary dentine diseases. DSPP is catalysed into dentine glycoprotein (DGP)/sialoprotein (DSP) and phosphoprotein (DPP) by proteolysis. DSP is further processed towards active molecules. DPP contains an RGD motif and abundant Ser-Asp/Asp-Ser repeat regions. DPP-RGD motif binds to integrin αVβ3 and activates intracellular signalling via mitogen-activated protein kinase (MAPK) and focal adhesion kinase (FAK)-ERK pathways. Unlike other SIBLING proteins, DPP lacks the RGD motif in some species. However, DPP Ser-Asp/Asp-Ser repeat regions bind to calcium-phosphate deposits and promote hydroxyapatite crystal growth and mineralisation via calmodulin-dependent protein kinase II (CaMKII) cascades. DSP lacks the RGD site but contains signal peptides. The tripeptides of the signal domains interact with cargo receptors within the endoplasmic reticulum that facilitate transport of DSPP from the endoplasmic reticulum to the extracellular matrix. Furthermore, the middle- and COOH-terminal regions of DSP bind to cellular membrane receptors, integrin β6 and occludin, inducing cell differentiation. The present review may shed light on DSPP roles during odontogenesis.
Topics: Cell Differentiation; Dental Pulp; Dentin; Extracellular Matrix Proteins; Odontoblasts; Phosphoproteins; Sialoglycoproteins
PubMed: 34275129
DOI: 10.22203/eCM.v042a04 -
Biomolecules Feb 2022The aim of this systematic review was to evaluate the application of potential therapeutic signaling molecules on complete dentin-pulp complex and pulp tissue... (Review)
Review
The aim of this systematic review was to evaluate the application of potential therapeutic signaling molecules on complete dentin-pulp complex and pulp tissue regeneration in orthotopic and ectopic animal studies. A search strategy was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement in the MEDLINE/PubMed database. Animal studies evaluating the application of signaling molecules to pulpectomized teeth for pulp tissue or dentin-pulp complex regeneration were included. From 2530 identified records, 18 fulfilled the eligibility criteria and were subjected to detailed qualitative analysis. Among the applied molecules, basic fibroblast growth factor, vascular endothelial growth factor, bone morphogenetic factor-7, nerve growth factor, and platelet-derived growth factor were the most frequently studied. The clinical, radiographical and histological outcome measures included healing of periapical lesions, root development, and apical closure, cellular recolonization of the pulp space, ingrowth of pulp-like connective tissue (vascularization and innervation), mineralized dentin-like tissue formation along the internal dentin walls, and odontoblast-like cells in contact with the internal dentin walls. The results indicate that signaling molecules play an important role in dentin/pulp regeneration. However, further studies are needed to determine a more specific subset combination of molecules to achieve greater efficiency towards the desired tissue engineering applications.
Topics: Animals; Dental Pulp; Dentin; Regeneration; Tissue Engineering; Vascular Endothelial Growth Factor A
PubMed: 35204786
DOI: 10.3390/biom12020285 -
Biomimetics (Basel, Switzerland) Oct 2023Assessing the biocompatibility of endodontic root-end filling materials through cell line responses is both essential and of utmost importance. This study aimed to the...
Assessing the biocompatibility of endodontic root-end filling materials through cell line responses is both essential and of utmost importance. This study aimed to the cytotoxicity of the type of cell death through apoptosis and autophagy, and odontoblast cell-like differentiation effects of MTA, zinc oxide-eugenol, and two experimental Portland cements modified with bismuth (Portland Bi) and barium (Portland Ba) on primary cell cultures. Material and methods: The cells corresponded to human periodontal ligament and gingival fibroblasts (HPLF, HGF), human pulp cells (HPC), and human squamous carcinoma cells from three different patients (HSC-2, -3, -4). The cements were inoculcated in different concentrations for cytotoxicity evaluation, DNA fragmentation in electrophoresis, apoptosis caspase activation, and autophagy antigen reaction, odontoblast-like cells were differentiated and tested for mineral deposition. The data were subject to a non-parametric test. Results: All cements caused a dose-dependent reduction in cell viability. Contact with zinc oxide-eugenol induced neither DNA fragmentation nor apoptotic caspase-3 activation and autophagy inhibitors (3-methyladenine, bafilomycin). Portland Bi accelerated significantly ( < 0.05) the differentiation of odontoblast-like cells. Within the limitation of this study, it was concluded that Portland cement with bismuth exhibits cytocompatibility and promotes odontoblast-like cell differentiation. This research contributes valuable insights into biocompatibility, suggesting its potential use in endodontic repair and biomimetic remineralization.
PubMed: 37999155
DOI: 10.3390/biomimetics8070514 -
Journal of Oral Biosciences Mar 2020The Bone Morphogenetic Proteins (BMPs) direct tooth development and still express in the adult tooth. We hypothesized that inhibition of BMP function would therefore...
OBJECTIVES
The Bone Morphogenetic Proteins (BMPs) direct tooth development and still express in the adult tooth. We hypothesized that inhibition of BMP function would therefore disrupt dentinogenesis by differentiated odontoblasts.
METHODS
We generated mice overexpressing the BMP-inhibitory protein Noggin in differentiated odontoblasts and osteocytes under control of a Dmp1 promoter-driven cre transgene. We compared the dentin phenotype in these mice with that in WT littermates and in mice with a Smad4 odontoblast/osteocyte knockout mediated by the same cre and therefore lacking all BMP and Tgfβ signaling in the same tissues.
RESULTS
Three-month-old first molars from both Noggin-expressing and Smad4-deleted mice showed decreased dentin volume with enlarged pulp cavities, and both displayed less organized and mineralized dentinal tubules compared to WT. The Smad4-ablated phenotype was more severe. While dentin sialophosphoprotein (DSPP) and bone sialoprotein (BSP) were decreased in the dentin of both lines, dentin matrix protein 1 (DMP1) was sharply increased in Noggin-expressing teeth.
CONCLUSIONS
The phenotypes we observed in Noggin-overexpressing and Smad4-conditional knockout teeth resemble the phenotype of Dentinogenesis Imperfecta (DGI) type III. Our results show that BMPs regulate post-natal dentinogenesis and that BMP-inhibitory proteins like Noggin play a role in that regulation. The increased severity of the Smad4 phenotype indicates that Tgfβ ligands, in addition to BMPs, play a crucial role in post-developmental dentinogenesis.
Topics: Animals; Carrier Proteins; Dentin; Dentinogenesis; Extracellular Matrix Proteins; Mice; Phosphoproteins; Sialoglycoproteins
PubMed: 31862386
DOI: 10.1016/j.job.2019.11.001 -
Journal of Bone and Mineral Research :... Feb 2022Considerable amount of research has been focused on dentin mineralization, odontoblast differentiation, and their application in dental tissue engineering. However, very...
Considerable amount of research has been focused on dentin mineralization, odontoblast differentiation, and their application in dental tissue engineering. However, very little is known about the differential role of functionally and spatially distinct types of dental epithelium during odontoblast development. Here we show morphological and functional differences in dentin located in the crown and roots of mouse molar and analogous parts of continuously growing incisors. Using a reporter (DSPP-cerulean/DMP1-cherry) mouse strain and mice with ectopic enamel (Spry2 ;Spry4 ), we show that the different microstructure of dentin is initiated in the very beginning of dentin matrix production and is maintained throughout the whole duration of dentin growth. This phenomenon is regulated by the different inductive role of the adjacent epithelium. Thus, based on the type of interacting epithelium, we introduce more generalized terms for two distinct types of dentins: cementum versus enamel-facing dentin. In the odontoblasts, which produce enamel-facing dentin, we identified uniquely expressed genes (Dkk1, Wisp1, and Sall1) that were either absent or downregulated in odontoblasts, which form cementum-facing dentin. This suggests the potential role of Wnt signalling on the dentin structure patterning. Finally, we show the distribution of calcium and magnesium composition in the two developmentally different types of dentins by utilizing spatial element composition analysis (LIBS). Therefore, variations in dentin inner structure and element composition are the outcome of different developmental history initiated from the very beginning of tooth development. Taken together, our results elucidate the different effects of dental epithelium, during crown and root formation on adjacent odontoblasts and the possible role of Wnt signalling which together results in formation of dentin of different quality. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Animals; Cell Differentiation; Dentin; Epithelium; Extracellular Matrix Proteins; Incisor; Mice; Odontoblasts; Odontogenesis
PubMed: 34783080
DOI: 10.1002/jbmr.4471 -
Journal of Clinical Medicine Jul 2021The dental pulp is a soft connective tissue of ectomesenchymal origin that harbors distinct cell populations, capable of interacting with each other to maintain the... (Review)
Review
The dental pulp is a soft connective tissue of ectomesenchymal origin that harbors distinct cell populations, capable of interacting with each other to maintain the vitality of the tooth. After tooth injuries, a sequence of complex biological events takes place in the pulpal tissue to restore its homeostasis. The pulpal response begins with establishing an inflammatory reaction that leads to the formation of a matrix of reactionary or reparative dentin, according to the nature of the exogenous stimuli. Using several in vivo designs, antigen-presenting cells, including macrophages and dendritic cells (DCs), are identified in the pulpal tissue before tertiary dentin deposition under the afflicted area. However, the precise nature of this phenomenon and its relationship to inherent pulp cells are not yet clarified. This literature review aims to discuss the role of pulpal DCs and their relationship to progenitor/stem cells, odontoblasts or odontoblast-like cells, and other immunocompetent cells during physiological and pathological dentinogenesis. The concept of "dentin-pulp immunology" is proposed for understanding the crosstalk among these cell types after tooth injuries, and the possibility of immune-based therapies is introduced to accelerate pulpal healing after exogenous stimuli.
PubMed: 34362130
DOI: 10.3390/jcm10153348 -
Journal of Oral Science 2020Dental pulp is densely innervated by sensory afferents that are primarily involved in nociception. Elucidating the type and properties of these afferents and their... (Review)
Review
Dental pulp is densely innervated by sensory afferents that are primarily involved in nociception. Elucidating the type and properties of these afferents and their distribution patterns within the dental pulp is crucial for understanding the mechanisms of acute dental pain and dental hypersensitivity. Recent studies on the release of the transmitter glutamate and the expression of glutamate receptors and vesicular glutamate transporters (VGLUT) in the pulpal axons and trigeminal ganglion (TG) have suggested the possibility of a distinct glutamate signaling mechanism underlying the peripheral processing of dental pain. This review discusses recent findings on the innervation of dental pulp and glutamate signaling by pulpal axons. First, recent findings on the morphological features and types of axons innervating the dental pulp are summarized. Then, glutamate signaling in the dental pulp and changes in the expression of VGLUT1 and VGLUT2 in the pulpal axons and TG neurons following pulpal inflammation are explained. Finally, findings on glutamate release from odontoblasts are briefly described.
Topics: Animals; Dental Pulp; Odontoblasts; Pain; Rats; Rats, Sprague-Dawley; Trigeminal Ganglion
PubMed: 32224566
DOI: 10.2334/josnusd.19-0451 -
The Journal of Biological Chemistry Aug 2022WW domain-containing E3 Ubiquitin-protein ligase 2 (WWP2) has been found to positively regulate odontoblastic differentiation by monoubiquitinating the transcription...
WW domain-containing E3 Ubiquitin-protein ligase 2 (WWP2) has been found to positively regulate odontoblastic differentiation by monoubiquitinating the transcription factor Kruppel-like factor 5 (KLF5) in a cell culture system. However, the in vivo role of WWP2 in mouse teeth remains unknown. To explore this, here we generated Wwp2 knockout (Wwp2 KO) mice. We found that molars in Wwp2 KO mice exhibited thinner dentin, widened predentin, and reduced numbers of dentinal tubules. In addition, expression of the odontoblast differentiation markers Dspp and Dmp1 was decreased in the odontoblast layers of Wwp2 KO mice. These findings demonstrate that WWP2 may facilitate odontoblast differentiation and dentinogenesis. Furthermore, we show for the first time that phosphatase and tensin homolog (PTEN), a tumor suppressor, is expressed in dental papilla cells and odontoblasts of mouse molars and acts as a negative regulator of odontoblastic differentiation. Further investigation indicated that PTEN is targeted by WWP2 for degradation during odontoblastic differentiation. We demonstrate PTEN physically interacts with and inhibits the transcriptional activity of KLF5 on Dspp and Dmp1. Finally, we found WWP2 was able to suppress the interaction between PTEN and KLF5, which diminished the inhibition effect of PTEN on KLF5. Taken together, this study confirms the essential role of WWP2 and the WWP2-PTEN-KLF5 signaling axis in odontoblast differentiation and dentinogenesis in vivo.
Topics: Animals; Cell Differentiation; Dentin; Dentinogenesis; Extracellular Matrix Proteins; Kruppel-Like Transcription Factors; Mice; Mice, Knockout; Odontoblasts; PTEN Phosphohydrolase; Phosphoproteins; Sialoglycoproteins; Signal Transduction; Transcription Factors; Ubiquitin-Protein Ligases
PubMed: 35780838
DOI: 10.1016/j.jbc.2022.102220 -
Frontiers in Cell and Developmental... 2023Dental mesenchymal stem cells (DMSCs) are multipotent progenitor cells that can differentiate into multiple lineages including odontoblasts, osteoblasts, chondrocytes,... (Review)
Review
Dental mesenchymal stem cells (DMSCs) are multipotent progenitor cells that can differentiate into multiple lineages including odontoblasts, osteoblasts, chondrocytes, neural cells, myocytes, cardiomyocytes, adipocytes, endothelial cells, melanocytes, and hepatocytes. Odontoblastic differentiation of DMSCs is pivotal in dentinogenesis, a delicate and dynamic process regulated at the molecular level by signaling pathways, transcription factors, and posttranscriptional and epigenetic regulation. Mutations or dysregulation of related genes may contribute to genetic diseases with dentin defects caused by impaired odontoblastic differentiation, including tricho-dento-osseous (TDO) syndrome, X-linked hypophosphatemic rickets (XLH), Raine syndrome (RS), hypophosphatasia (HPP), Schimke immuno-osseous dysplasia (SIOD), and Elsahy-Waters syndrome (EWS). Herein, recent progress in the molecular regulation of the odontoblastic differentiation of DMSCs is summarized. In addition, genetic syndromes associated with disorders of odontoblastic differentiation of DMSCs are discussed. An improved understanding of the molecular regulation and related genetic syndromes may help clinicians better understand the etiology and pathogenesis of dentin lesions in systematic diseases and identify novel treatment targets.
PubMed: 37818127
DOI: 10.3389/fcell.2023.1174579 -
Journal of Clinical Medicine Sep 2022Cell cultures can provide useful in vitro models. Since odontoblasts are postmitotic cells, they cannot be expanded in cell cultures. Due to their extension into the... (Review)
Review
Cell cultures can provide useful in vitro models. Since odontoblasts are postmitotic cells, they cannot be expanded in cell cultures. Due to their extension into the dentin, injuries are inevitable during isolation. Therefore, "odontoblast-like" cell culture models have been established. Nowadays, there is no accepted definition of odontoblast-like cell cultures, i.e., isolation, induction, and characterization of cells are not standardized. Furthermore, no quality-control procedures are defined yet. Thus, the aim of this review was to evaluate both the methods used for establishment of cell cultures and the validity of molecular methods used for their characterization. An electronic search was performed in February 2022 using the Medline, Scopus, and Web of Science database identifying publications that used human primary odontoblast-like cell cultures as models and were published between 2016 and 2022. Data related to (I) cell culture conditions, (II) stem cell screening, (III) induction media, (IV) mineralization, and (V) cell characterization were analyzed. The included publications were not able to confirm an odontoblast-like nature of their cell cultures. For their characterization, not only a similarity to dentin but also a distinction from bone must be demonstrated. This is challenging, due to the developmental and evolutionary proximity of these two tissue types.
PubMed: 36142943
DOI: 10.3390/jcm11185296