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Physiological Reviews Jul 2017Dental enamel is the hardest and most mineralized tissue in extinct and extant vertebrate species and provides maximum durability that allows teeth to function as... (Review)
Review
Dental enamel is the hardest and most mineralized tissue in extinct and extant vertebrate species and provides maximum durability that allows teeth to function as weapons and/or tools as well as for food processing. Enamel development and mineralization is an intricate process tightly regulated by cells of the enamel organ called ameloblasts. These heavily polarized cells form a monolayer around the developing enamel tissue and move as a single forming front in specified directions as they lay down a proteinaceous matrix that serves as a template for crystal growth. Ameloblasts maintain intercellular connections creating a semi-permeable barrier that at one end (basal/proximal) receives nutrients and ions from blood vessels, and at the opposite end (secretory/apical/distal) forms extracellular crystals within specified pH conditions. In this unique environment, ameloblasts orchestrate crystal growth via multiple cellular activities including modulating the transport of minerals and ions, pH regulation, proteolysis, and endocytosis. In many vertebrates, the bulk of the enamel tissue volume is first formed and subsequently mineralized by these same cells as they retransform their morphology and function. Cell death by apoptosis and regression are the fates of many ameloblasts following enamel maturation, and what cells remain of the enamel organ are shed during tooth eruption, or are incorporated into the tooth's epithelial attachment to the oral gingiva. In this review, we examine key aspects of dental enamel formation, from its developmental genesis to the ever-increasing wealth of data on the mechanisms mediating ionic transport, as well as the clinical outcomes resulting from abnormal ameloblast function.
Topics: Ameloblasts; Amelogenesis; Animals; Dental Enamel; Dental Enamel Proteins; Evolution, Molecular; Genetic Predisposition to Disease; Humans; Oral Health; Phenotype; Species Specificity; Tooth Abnormalities; Tooth Diseases
PubMed: 28468833
DOI: 10.1152/physrev.00030.2016 -
Calcified Tissue International Nov 2017Amelogenesis (tooth enamel formation) is a biomineralization process consisting primarily of two stages (secretory stage and maturation stage) with unique features.... (Review)
Review
Amelogenesis (tooth enamel formation) is a biomineralization process consisting primarily of two stages (secretory stage and maturation stage) with unique features. During the secretory stage, the inner epithelium of the enamel organ (i.e., the ameloblast cells) synthesizes and secretes enamel matrix proteins (EMPs) into the enamel space. The protein-rich enamel matrix forms a highly organized architecture in a pH-neutral microenvironment. As amelogenesis transitions to maturation stage, EMPs are degraded and internalized by ameloblasts through endosomal-lysosomal pathways. Enamel crystallite formation is initiated early in the secretory stage, however, during maturation stage the more rapid deposition of calcium and phosphate into the enamel space results in a rapid expansion of crystallite length and mineral volume. During maturation-stage amelogenesis, the pH value of enamel varies considerably from slightly above neutral to acidic. Extracellular acid-base balance during enamel maturation is tightly controlled by ameloblast-mediated regulatory networks, which include significant synthesis and movement of bicarbonate ions from both the enamel papillary layer cells and ameloblasts. In this review we summarize the carbonic anhydrases and the carbonate transporters/exchangers involved in pH regulation in maturation-stage amelogenesis. Proteins that have been shown to be instrumental in this process include CA2, CA6, CFTR, AE2, NBCe1, SLC26A1/SAT1, SLC26A3/DRA, SLC26A4/PDS, SLC26A6/PAT1, and SLC26A7/SUT2. In addition, we discuss the association of miRNA regulation with bicarbonate transport in tooth enamel formation.
Topics: Amelogenesis; Animals; Anion Transport Proteins; Bicarbonates; Biological Transport; Carbonic Anhydrases; Chloride-Bicarbonate Antiporters; Cystic Fibrosis Transmembrane Conductance Regulator; Dental Enamel; Humans; MicroRNAs; Sodium-Bicarbonate Symporters
PubMed: 28795233
DOI: 10.1007/s00223-017-0311-2 -
Frontiers in Physiology 2017Enamel formation requires consecutive stages of development to achieve its characteristic extreme mineral hardness. Mineralization depends on the initial presence then... (Review)
Review
Enamel formation requires consecutive stages of development to achieve its characteristic extreme mineral hardness. Mineralization depends on the initial presence then removal of degraded enamel proteins from the matrix via endocytosis. The ameloblast membrane resides at the interface between matrix and cell. Enamel formation is controlled by ameloblasts that produce enamel in stages to build the enamel layer (secretory stage) and to reach final mineralization (maturation stage). Each stage has specific functional requirements for the ameloblasts. Ameloblasts adopt different cell morphologies during each stage. Protein trafficking including the secretion and endocytosis of enamel proteins is a fundamental task in ameloblasts. The sites of internalization of enamel proteins on the ameloblast membrane are specific for every stage. In this review, an overview of endocytosis and trafficking of vesicles in ameloblasts is presented. The pathways for internalization and routing of vesicles are described. Endocytosis is proposed as a mechanism to remove debris of degraded enamel protein and to obtain feedback from the matrix on the status of the maturing enamel.
PubMed: 28824442
DOI: 10.3389/fphys.2017.00529 -
Frontiers in Physiology 2014While many effectors have been identified in enamel matrix and cells via genetic studies, physiological networks underlying their expression levels and thus the natural... (Review)
Review
While many effectors have been identified in enamel matrix and cells via genetic studies, physiological networks underlying their expression levels and thus the natural spectrum of enamel thickness and degree of mineralization are now just emerging. Several transcription factors are candidates for enamel gene expression regulation and thus the control of enamel quality. Some of these factors, such as MSX2, are mainly confined to the dental epithelium. MSX2 homeoprotein controls several stages of the ameloblast life cycle. This chapter introduces MSX2 and its target genes in the ameloblast and provides an overview of knowledge regarding its effects in vivo in transgenic mouse models. Currently available in vitro data on the role of MSX2 as a transcription factor and its links to other players in ameloblast gene regulation are considered. MSX2 modulations are relevant to the interplay between developmental, hormonal and environmental pathways and in vivo investigations, notably in the rodent incisor, have provided insight into dental physiology. Indeed, in vivo models are particularly promising for investigating enamel formation and MSX2 function in ameloblast cell fate. MSX2 may be central to the temporal-spatial restriction of enamel protein production by the dental epithelium and thus regulation of enamel quality (thickness and mineralization level) under physiological and pathological conditions. Studies on MSX2 show that amelogenesis is not an isolated process but is part of the more general physiology of coordinated dental-bone complex growth.
PubMed: 25601840
DOI: 10.3389/fphys.2014.00510 -
Experimental Cell Research Jul 2014Although a big deal of dental research is being focused to the understanding of early stages of tooth development, a huge gap exist on our knowledge on how the dental... (Review)
Review
Although a big deal of dental research is being focused to the understanding of early stages of tooth development, a huge gap exist on our knowledge on how the dental hard tissues are formed and how this process is controlled daily in order to produce very complex and diverse tooth shapes adapted for specific functions. Emerging evidence suggests that clock genes, a family of genes that controls circadian functions within our bodies, regulate also dental mineralized tissues formation. Enamel formation, for example, is subjected to rhythmical molecular signals that occur on short (24h) periods and control the secretion and maturation of the enamel matrix. Accordingly, gene expression and ameloblast functions are also tightly modulated in regular daily intervals. This review summarizes the current knowledge on the circadian controls of dental mineralized tissues development with a special emphasis on amelogenesis.
Topics: Amelogenesis; Animals; Cell Differentiation; Circadian Rhythm; Dental Enamel; Humans; Odontogenesis
PubMed: 24582863
DOI: 10.1016/j.yexcr.2014.02.007 -
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 -
ELife May 2023Single-cell transcriptome analysis of zebrafish cells clarifies the signalling pathways controlling skin formation and reveals that some cells produce proteins required...
Single-cell transcriptome analysis of zebrafish cells clarifies the signalling pathways controlling skin formation and reveals that some cells produce proteins required for human teeth to acquire their enamel.
Topics: Animals; Humans; Ameloblasts; Zebrafish; Tooth
PubMed: 37218526
DOI: 10.7554/eLife.88597 -
The Japanese Dental Science Review May 2016During tooth development, ameloblasts differentiate from inner enamel epithelial cells to enamel-forming cells by modulating the signal pathways mediating... (Review)
Review
During tooth development, ameloblasts differentiate from inner enamel epithelial cells to enamel-forming cells by modulating the signal pathways mediating epithelial-mesenchymal interaction and a cell-autonomous gene network. The differentiation process of epithelial cells is characterized by marked changes in their morphology and polarity, accompanied by dynamic cytoskeletal reorganization and changes in cell-cell and cell-matrix adhesion over time. Functional ameloblasts are tall, columnar, polarized cells that synthesize and secrete enamel-specific proteins. After deposition of the full thickness of enamel matrix, ameloblasts become smaller and regulate enamel maturation. Recent significant advances in the fields of molecular biology and genetics have improved our understanding of the regulatory mechanism of the ameloblast cell life cycle, mediated by the Rho family of small GTPases. They act as intracellular molecular switch that transduce signals from extracellular stimuli to the actin cytoskeleton and the nucleus. In our review, we summarize studies that provide current evidence for Rho GTPases and their involvement in ameloblast differentiation. In addition to the Rho GTPases themselves, their downstream effectors and upstream regulators have also been implicated in ameloblast differentiation.
PubMed: 28408954
DOI: 10.1016/j.jdsr.2015.09.001 -
Frontiers in Physiology 2023Enamel mineralization requires calcium transport into the extracellular matrix for the synthesis of hydroxyapatite (HA) crystals. Formation of HA releases protons into...
Enamel mineralization requires calcium transport into the extracellular matrix for the synthesis of hydroxyapatite (HA) crystals. Formation of HA releases protons into the matrix, which are then neutralized when ameloblasts modulate from cells with apical invaginations, the so-called ruffle-ended ameloblasts (RE), to smooth-ended ameloblasts (SE). Ameloblast modulation is associated with the translocation of the calcium exchanger Nckx4 to the apical border of RE, to remove Na from the enamel matrix in exchange for Ca and K. As enamel matures, Na and K in the matrix progressively decrease. However, the transporter to remove K from mineralizing enamel has not been identified. Expression of K exchangers and channels in secretory and maturation stage of enamel organs were compared following an RNA-seq analysis. Kcnj15, which encodes the Kir4.2 inwardly rectifying K channel, was found to be the most upregulated internalizing K transporter in maturation stage of enamel organs. Kir4.2 was immunolocalized in wt, Nckx4, Wdr72, and fluorosed ameloblasts. Regulation of Wdr72 expression by pH was characterized and . Kir4.2 immunolocalized to the apical border of wild type (wt) mouse RE and cytosol of SE, a spatial distribution pattern shared by NCKX4. In Nckx4 ameloblasts, Kir4.2 also localized to the apical surface of RE and cytosol of SE. However, in fluorosed and Wdr72 ameloblasts, in which vesicle trafficking is disrupted, Kir4.2 remained in the cytosol. , Wdr72 was upregulated in LS8 cells cultured in medium with a pH 6.2, which is the pH of the enamel matrix underlying RE, as compared to pH 7.2 under SE. Taken together these results suggest that Kir4.2 participates in K uptake by maturation ameloblasts, and that K and Na uptake by Kir4.2 and Nckx4, respectively, may be regulated by pH through WDR72-mediated endocytosis and membrane trafficking.
PubMed: 36814472
DOI: 10.3389/fphys.2023.1124444 -
The International Journal of... Feb 1995This review highlights a number of advances towards understanding the sequential developmental cascade of events beginning in the oral ectodermally-derived odontogenic... (Review)
Review
This review highlights a number of advances towards understanding the sequential developmental cascade of events beginning in the oral ectodermally-derived odontogenic placode and culminating in the formation of the mineralized enamel extracellular matrix. Recent discoveries of growth factors, growth factor receptors and transcription factors associated with instructive epithelial-mesenchymal interactions and subsequent controls for ameloblast cell differentiation are reviewed. The relationship between ameloblast cytology, terminal differentiation and biochemical phenotype are discussed. The tissue-specific gene products characteristic of the ameloblast phenotype as well as their possible functions in formation of the enamel matrix are analyzed as well as the role of maturation-stage ameloblast cells in controlling enamel biomineralization. Finally, pathological conditions in which alterations in the ameloblast or specific gene products result in an abnormal enamel phenotype are reviewed. Clearly, the scientific progress achieved in the last few years concerning the molecular determinants involved in tooth development has been remarkable. However, there remains considerable lack of knowledge regarding the precise mechanisms that control ameloblast differentiation and enamel biomineralization. Anticipated progress continues to require increased international cooperation and collaborations as well as increased utilization of structural biology investigations of enamel extracellular matrix proteins.
Topics: Ameloblasts; Amelogenin; Amino Acid Sequence; Animals; Cell Differentiation; Dental Enamel Proteins; Gene Expression Regulation; Growth Substances; Humans; Molecular Sequence Data; Odontogenesis; Transcription Factors
PubMed: 7626423
DOI: No ID Found