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The Chinese Journal of Dental Research Jun 2021Wnt signalling pathways have been the focus of intense research activity for decades due to their fundamental role in skeletal and dental development. Wntless, an... (Review)
Review
Wnt signalling pathways have been the focus of intense research activity for decades due to their fundamental role in skeletal and dental development. Wntless, an exclusive chaperone protein for the exocytotis of Wnt ligands, was identified in 2006. In the last decade, the molecular biological studies of Wntless and its genetic studies in human and mice have highlighted the importance of this protein in mineralised tissues, including bone, cartilage and teeth. This article reviews recent developments and discrepancies in the role of Wntless in skeletal and dental development based on mutant phenotypes, as well as the underlying mechanism involved in its molecular and physiological regulation. We conclude that, though some controversial phenotypes exist due to different Cre line resources, Cre recombinase activity and detection time points, Wntless undeniably exerts a context- and stage-dependent regulatory function during the development and homeostasis of both skeletal and dental tissue.
Topics: Animals; Humans; Mice; Odontogenesis; Osteogenesis; Tooth; Wnt Signaling Pathway
PubMed: 34219441
DOI: 10.3290/j.cjdr.b1530533 -
International Journal of Molecular... Feb 2022Leptin is a non-glycosylated 16 kDa protein synthesized mainly in adipose cells. The main function of leptin is to regulate energy homeostasis and weight control in a... (Review)
Review
Leptin is a non-glycosylated 16 kDa protein synthesized mainly in adipose cells. The main function of leptin is to regulate energy homeostasis and weight control in a central manner. There is increasing evidence that leptin also has systemic effects, acting as a link between innate and acquired immune responses. The expression of leptin and its receptor in human dental pulp and periradicular tissues have already been described, as well as several stimulatory effects of leptin protein expression in dental and periodontal tissues. The aim of this paper was to review and to compile the reported scientific literature on the role and effects of leptin in the dental pulp and periapical tissues. Twelve articles accomplished the inclusion criteria, and a comprehensive narrative review was carried out. Review of the available scientific literature concluded that leptin has the following effects on pulpal and periapical physiology: 1) Stimulates odontogenic differentiation of dental pulp stem cells (DPSCs), 2) Increases the expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1), odontoblastic proteins involved in odontoblastic differentiation and dentin mineralization, 3) Stimulates vascular endothelial growth factor (VEGF) expression in human dental pulp tissue and primary cultured cells of human dental pulp (hDPCs), 4) Stimulates angiogenesis in rat dental pulp cells, and 5) Induces the expression of interleucinas 6 and 8 in human periodontal ligament cells (hPDLCs). There is evidence which suggests that leptin is implicated in the dentin mineralization process and in pulpal and periapical inflammatory and reparative responses.
Topics: Animals; Cell Differentiation; Dental Pulp; Humans; Leptin; Odontogenesis; Periodontal Ligament
PubMed: 35216099
DOI: 10.3390/ijms23041984 -
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 -
JBMR Plus Mar 2021Micro-computed tomography (μCT) has become essential for analysis of mineralized as well as nonmineralized tissues and is therefore widely applicable in the life... (Review)
Review
Micro-computed tomography (μCT) has become essential for analysis of mineralized as well as nonmineralized tissues and is therefore widely applicable in the life sciences. However, lack of standardized approaches and protocols for scanning, analyzing, and reporting data often makes it difficult to understand exactly how analyses were performed, how to interpret results, and if findings can be broadly compared with other models and studies. This problem is compounded in analysis of the dentoalveolar complex by the presence of four distinct mineralized tissues: enamel, dentin, cementum, and alveolar bone. Furthermore, these hard tissues interface with adjacent soft tissues, the dental pulp and periodontal ligament (PDL), making for a complex organ. Drawing on others' and our own experience analyzing rodent dentoalveolar tissues by μCT, we introduce techniques to successfully analyze dentoalveolar tissues with similar or disparate compositions, densities, and morphological characteristics. Our goal is to provide practical guidelines for μCT analysis of rodent dentoalveolar tissues, including approaches to optimize scan parameters (filters, voltage, voxel size, and integration time), reproducibly orient samples, define regions and volumes of interest, segment and subdivide tissues, interpret findings, and report methods and results. We include illustrative examples of analyses performed on genetically engineered mouse models with phenotypes in enamel, dentin, cementum, and alveolar bone. The recommendations are designed to increase transparency and reproducibility, promote best practices, and provide a basic framework to apply μCT analysis to the dentoalveolar complex that can also be extrapolated to a variety of other tissues of the body. © 2021 The Authors. published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
PubMed: 33778330
DOI: 10.1002/jbm4.10474 -
Organogenesis Dec 2023It is known to all that Wnt signaling pathway plays an important role in the early development of tooth. Our previous research found that Wnt signaling pathway played... (Review)
Review
It is known to all that Wnt signaling pathway plays an important role in the early development of tooth. Our previous research found that Wnt signaling pathway played crucial roles in dental development, and mutations in antagonist of Wnt signaling pathway may lead to the formation of supernumerary teeth. However, the expression pattern of Wnt signaling molecules in early development of tooth, especially genes with stage specificity, remains unclear. Hence, we applied RNA-seq analysis to determine the expression levels of wnt signal molecules at five different stages of rat first molar tooth germ. In addition, after literature review we summarized the function of Wnt signaling molecules during tooth development and the relationship between Wnt signaling molecules variation and tooth agenesis. Our research may have implications for exploring the role of Wnt signaling molecules in different stages of tooth development.
Topics: Rats; Animals; Wnt Signaling Pathway; Odontogenesis; Wnt Proteins; Tooth; Molar
PubMed: 37194731
DOI: 10.1080/15476278.2023.2212583 -
International Journal of Oral Science May 2021Circadian rhythm is involved in the development and diseases of many tissues. However, as an essential environmental regulating factor, its effect on amelogenesis has...
Circadian rhythm is involved in the development and diseases of many tissues. However, as an essential environmental regulating factor, its effect on amelogenesis has not been fully elucidated. The present study aims to investigate the correlation between circadian rhythm and ameloblast differentiation and to explore the mechanism by which circadian genes regulate ameloblast differentiation. Circadian disruption models were constructed in mice for in vivo experiments. An ameloblast-lineage cell (ALC) line was used for in vitro studies. As essential molecules of the circadian system, Bmal1 and Per2 exhibited circadian expression in ALCs. Circadian disruption mice showed reduced amelogenin (AMELX) expression and enamel matrix secretion and downregulated expression of BMAL1, PER2, PPARγ, phosphorylated AKT1 and β-catenin, cytokeratin-14 and F-actin in ameloblasts. According to previous findings and our study, BMAL1 positively regulated PER2. Therefore, the present study focused on PER2-mediated ameloblast differentiation and enamel formation. Per2 knockdown decreased the expression of AMELX, PPARγ, phosphorylated AKT1 and β-catenin, promoted nuclear β-catenin accumulation, inhibited mineralization and altered the subcellular localization of E-cadherin in ALCs. Overexpression of PPARγ partially reversed the above results in Per2-knockdown ALCs. Furthermore, in in vivo experiments, the length of incisor eruption was significantly decreased in the circadian disturbance group compared to that in the control group, which was rescued by using a PPARγ agonist in circadian disturbance mice. In conclusion, through regulation of the PPARγ/AKT1/β-catenin signalling axis, PER2 played roles in amelogenin expression, cell junctions and arrangement, enamel matrix secretion and mineralization during ameloblast differentiation, which exert effects on enamel formation.
Topics: Ameloblasts; Amelogenesis; Animals; Cell Differentiation; Mice; PPAR gamma; Period Circadian Proteins; beta Catenin
PubMed: 34011974
DOI: 10.1038/s41368-021-00123-7 -
International Dental Journal Jun 2023The differentiation of stem cells from exfoliated deciduous teeth (SHEDs) into odontoblasts determines the regeneration of dentin-pulp complex. Non-coding RNAs (ncRNAs),...
BACKGROUND
The differentiation of stem cells from exfoliated deciduous teeth (SHEDs) into odontoblasts determines the regeneration of dentin-pulp complex. Non-coding RNAs (ncRNAs), including microRNA (miRNA) and long non-coding RNA (lncRNA), participate in many multiple biological processes, but the specific miRNAs involved in odontogenesis are incompletely defined. It was confirmed that lncRNA IGFBP7-AS1 could positively regulate odontogenetic differentiation in SHEDs. To investigate the downstream mechanisms of this process, miR-335-3p and miR-155-5p were found to be closely related with SHED odontogenic differentiation through whole-genome sequencing. The aim of the current study was to determine the role of miR-335-3p/miR-155-5p in IGFBP7-AS1-enhanced SHED differentiation and explore the potential mechanism of IGFBP7-AS1-mediated odontogenesis.
METHODS
Putative miR-335-3p/miR-155-5p binding sites within IGFBP7-AS1 were identified by bioinformatics analysis, and the binding of miR-335-3p/miR-155-5p to these sites was confirmed by dual-luciferase reporter gene assays. The effects of miR-335-3p/miR-155-5p in odontogenesis were detected by tissue nonspecific alkaline phosphatase staining, Alizarin red staining, quantitative real-time polymerase chain reaction (qRT-PCR) analyses, and western blot testing. The molecular mechanisms of miR-335-3p/miR-155-5p involved in IGFBP7-AS1-mediated odontogenesis were analysed by qRT-PCR and western blot testing.
RESULTS
Dual-luciferase reporter gene assays showed that miR-335-3p/miR-155-5p could directly bind to IGFBP7-AS1. MiR-335-3p and miR-155-5p both could down-regulate dentin sialophosphoprotein expression, and both miRNAs could inhibit IGFBP7-AS1-mediated SHED odontogenetic differentiation via suppression of the extracellular signal-regulated kinase (ERK) pathway.
CONCLUSIONS
Both miR-335-3p and miR-155-5p were negative regulators to IGFBP7-AS1-enhanced odontogenic differentiation of SHED through suppression of the ERK pathway.
Topics: Humans; RNA, Long Noncoding; MicroRNAs; Cell Differentiation; Odontogenesis; Luciferases
PubMed: 35999071
DOI: 10.1016/j.identj.2022.07.008 -
Molecular Biology Reports Apr 2021Odontogenic tumors comprised of complex heterogeneous lesions that diverse from harmatomas to malignant tumors with different behavior and histology. The etiology of... (Review)
Review
Odontogenic tumors comprised of complex heterogeneous lesions that diverse from harmatomas to malignant tumors with different behavior and histology. The etiology of odontogenic tumors is not exactly determined and pathologists deal with challenges in diagnosis of odontogenic tumors because they are rare and obtained experiences are difficult to evaluate. In this study, we describe immunohistochemical and molecular markers in diagnosis of odontogenic tumors besides advanced diagnostic technique. Immunohistochemical features of odontogenic tumors beside the clinical features and radiological finding can help us to determine the correct diagnosis. Although these markers are neither specific nor sensitive enough, but analysis of gene expression provides definitive confirmation of diagnosis. In addition, "-omics" technology detected specific molecular alternation associated with etiology such as genomics, epigenomics, transcriptomics, proteomics and metabolomics. The post transcriptional events such as DNA methylation and chromatin remodeling by histone modification affect the changes in epigenome. Furthermore, non-coding RNAs like micro-RNAs, long noncoding RNA (lncRNA) and small non-coding RNA (snoRNA) play regulatory role and impact odontogenesis. Molecular marker propose their potential role in etiopathogenesis of odontogenic tumors and suitable candidate in diagnostic, prognostic and therapeutic approaches in addition to patient management. For future evaluations, organoid represents in vitro tumor model-study for tumor behavior, metastasis and invasion, drug screening, immunotherapy, clinical trial, hallmarks association with prognosis and evolution of personalized anti-cancer therapy. Moreover, organoid biobank help us to check genetic profile. We think more investigation and studies are needed to gain these knowledges that can shift therapeutic approaches to target therapy.
Topics: Biomarkers, Tumor; Genomics; Humans; Odontogenic Tumors
PubMed: 33822294
DOI: 10.1007/s11033-021-06286-0 -
Frontiers in Cell and Developmental... 2021The development of a tooth germ in a precise size, shape, and position in the jaw, involves meticulous regulation of cell proliferation and cell death. Apoptosis, as the... (Review)
Review
The development of a tooth germ in a precise size, shape, and position in the jaw, involves meticulous regulation of cell proliferation and cell death. Apoptosis, as the most common type of programmed cell death during embryonic development, plays a number of key roles during odontogenesis, ranging from the budding of the oral epithelium during tooth initiation, to later tooth germ morphogenesis and removal of enamel knot signaling center. Here, we summarize recent knowledge about the distribution and function of apoptotic cells during odontogenesis in several vertebrate lineages, with a special focus on amniotes (mammals and reptiles). We discuss the regulatory roles that apoptosis plays on various cellular processes during odontogenesis. We also review apoptosis-associated molecular signaling during tooth development, including its relationship with the autophagic pathway. Lastly, we cover apoptotic pathway disruption, and alterations in apoptotic cell distribution in transgenic mouse models. These studies foster a deeper understanding how apoptotic cells affect cellular processes during normal odontogenesis, and how they contribute to dental disorders, which could lead to new avenues of treatment in the future.
PubMed: 34222243
DOI: 10.3389/fcell.2021.671475 -
International Journal of Molecular... Nov 2020Dental enamel is hardest tissue in the body and is produced by dental epithelial cells residing in the tooth. Their cell fates are tightly controlled by transcriptional... (Review)
Review
Dental enamel is hardest tissue in the body and is produced by dental epithelial cells residing in the tooth. Their cell fates are tightly controlled by transcriptional programs that are facilitated by fate determining transcription factors and chromatin regulators. Understanding the transcriptional program controlling dental cell fate is critical for our efforts to build and repair teeth. In this review, we describe the current understanding of these regulators essential for regeneration of dental epithelial stem cells and progeny, which are identified through transgenic mouse models. We first describe the development and morphogenesis of mouse dental epithelium in which different subpopulations of epithelia such as ameloblasts contribute to enamel formation. Then, we describe the function of critical factors in stem cells or progeny to drive enamel lineages. We also show that gene mutations of these factors are associated with dental anomalies in craniofacial diseases in humans. We also describe the function of the master regulators to govern dental lineages, in which the genetic removal of each factor switches dental cell fate to that generating hair. The distinct and related mechanisms responsible for the lineage plasticity are discussed. This knowledge will lead us to develop a potential tool for bioengineering new teeth.
Topics: Ameloblasts; Animals; Cell Differentiation; Epithelial Cells; Epithelium; Gene Expression Regulation; Humans; Mice; Mice, Transgenic; Odontogenesis; Tooth; Transcription, Genetic
PubMed: 33255698
DOI: 10.3390/ijms21238952