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Central-European Journal of Immunology 2020Eating food is one of the most complicated behaviours in mammals, especially humans. The primary function of ghrelin is regulation of the appetite level and its... (Review)
Review
Eating food is one of the most complicated behaviours in mammals, especially humans. The primary function of ghrelin is regulation of the appetite level and its stimulation. It is also responsible for the body's energy balance and glucose homeostasis. Ghrelin has been shown to affect many brain structures, which confirms the presence of ghrelin receptors in the brain. Studies are also conducted to assess the possible role of ghrelin in anxiety states and in memory disorders and motor dysfunctions. Ghrelin has been found in saliva and salivary glands, teeth and gums, and in the taste buds of the tongue epithelium; it is also secreted by mucosal cells and gingival fibroblasts. The presence of ghrelin in developmental enamel, especially in odontoblasts and ameloblasts, may suggest its regulatory role in the development of teeth. Patients with chronic periodontitis have significantly higher concentrations of ghrelin in the peripheral blood serum, as compared to the control group. Ghrelin plays a special role in the proliferation of cancer cells and in the development of neoplastic metastases. The abundant presence of ghrelin receptors in cancer cells is considered an important target in the treatment of neoplasms. Ghrelin is a hormone whose multidirectional mechanism of action has not yet been fully understood. However, its ubiquitous occurrence in the human body and its very diverse participation in metabolic processes may prove to be a significant obstacle in achieving the expected clinical effect of ghrelin as an effective drug in selected disease units.
PubMed: 33613094
DOI: 10.5114/ceji.2020.103415 -
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 -
Frontiers in Physiology 2022ADAM10 is A Disintegrin And Metalloproteinase (ADAM) family member that is membrane bound with its catalytic domain present on the cell surface. It is a sheddase that... (Review)
Review
ADAM10 is A Disintegrin And Metalloproteinase (ADAM) family member that is membrane bound with its catalytic domain present on the cell surface. It is a sheddase that cleaves anchored cell surface proteins to shed them from the cell surface. ADAM10 can cleave at least a hundred different proteins and is expressed in most tissues of the body. ADAM10 is best characterized for its role in Notch signaling. Interestingly, ADAM10 is transported to specific sites on the cell surface by six different tetraspanins. Although the mechanism is not clear, tetraspanins can regulate ADAM10 substrate specificity, which likely contributes to the diversity of ADAM10 substrates. In developing mouse teeth, ADAM10 is expressed in the stem cell niche and subsequently in pre-ameloblasts and then secretory stage ameloblasts. However, once ameloblasts begin transitioning into the maturation stage, ADAM10 expression abruptly ceases. This is exactly when ameloblasts stop their movement that extends enamel crystallites and when the enamel layer reaches its full thickness. ADAM10 may play an important role in enamel development. ADAM10 can cleave cadherins and other cell-cell junctions at specific sites where the tetraspanins have transported it and this may promote cell movement. ADAM10 can also cleave the transmembrane proteins COL17A1 and RELT. When either or are mutated, malformed enamel may occur in humans and mice. So, ADAM10 may also regulate these proteins that are necessary for proper enamel development. This mini review will highlight ADAM10 function, how that function is regulated by tetraspanins, and how ADAM10 may promote enamel formation.
PubMed: 36505044
DOI: 10.3389/fphys.2022.1032383 -
Genes Feb 2023Dental enamel is a specialized tissue that has adapted over millions of years of evolution to enhance the survival of a variety of species. In humans, enamel evolved to... (Review)
Review
Dental enamel is a specialized tissue that has adapted over millions of years of evolution to enhance the survival of a variety of species. In humans, enamel evolved to form the exterior protective layer for the crown of the exposed tooth crown. Its unique composition, structure, physical properties and attachment to the underlying dentin tissue allow it to be a resilient, although not self-repairing, tissue. The process of enamel formation, known as amelogenesis, involves epithelial-derived cells called ameloblasts that secrete a unique extracellular matrix that influences the structure of the mineralizing enamel crystallites. There are over 115 known genetic conditions affecting amelogenesis that are associated with enamel phenotypes characterized by either a reduction of enamel amount and or mineralization. Amelogenesis involves many processes that are sensitive to perturbation and can be altered by numerous environmental stressors. Genetics, epigenetics, and environment factors can influence enamel formation and play a role in resistance/risk for developmental defects and the complex disease, dental caries. Understanding why and how enamel is affected and the enamel phenotypes seen clinically support diagnostics, prognosis prediction, and the selection of treatment approaches that are appropriate for the specific tissue defects (e.g., deficient amount, decreased mineral, reduced insulation and hypersensitivity). The current level of knowledge regarding the heritable enamel defects is sufficient to develop a new classification system and consensus nosology that effectively communicate the mode of inheritance, molecular defect/pathway, and the functional aberration and resulting enamel phenotype.
Topics: Humans; Dental Caries; Tooth; Ameloblasts; Phenotype; Dental Enamel
PubMed: 36980818
DOI: 10.3390/genes14030545 -
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 -
Health Science Reports Jan 2023Odontogenic cysts and tumors often form hard and soft structures that resemble odontogenesis. It is well known that amyloid is produced in Pindborg tumors; however, it...
BACKGROUND AND AIMS
Odontogenic cysts and tumors often form hard and soft structures that resemble odontogenesis. It is well known that amyloid is produced in Pindborg tumors; however, it is still debatable whether it is also formed in other odontogenic tumors and cysts. This study aimed to detect the presence of amyloid in different odontogenic cysts and tumors in correlation to matrix proteins secreted during enamel formation; namely amelogenin and odontogenic ameloblast-associated protein.
METHODS
This study included formalin fixed paraffin embedded tissue blocks of 106 different types of odontogenic cysts and tumors. Congo red and thioflavin T were performed to confirm the presence of amyloid; immunohistochemistry was used to detect amelogenin and odontogenic ameloblast-associated protein.
RESULTS
Amyloid was detected in pindborg tumors (conventional), adenomatoid odontogenic tumors, odontogenic fibroma (Amyloid variant), follicular solid and unicystic ameloblastomas, radicular cysts, dentigerous cysts, dentinogenic ghost cell odontogenic tumor, ameloblastic fibroma, calcifying odontogenic cyst, and primordial Odontogenic tumor. Amelogenin was detected in 95.3% of the cases, while odontogenic ameloblast-associated protein was detected in 93.4% of the cases. The association between odontogenic ameloblast-associated protein and amyloid was highly significant at < 0.01. However, there was no significant relationship between amelogenin and amyloid > 0.05.
CONCLUSION
Although pindborg tumor is the bonafide example of amyloid deposition in odontogenic tumors, this study concluded that amyloid may be deposited in traces to massive amounts in various odontogenic cysts and tumors, and it is significantly linked to odontogenic ameloblast-associated protein but not amelogenin matrix protein, since all amyloid cases were odontogenic ameloblast associated protein positive.
PubMed: 36655142
DOI: 10.1002/hsr2.1061 -
Journal of Dental Research Aug 2021The systematic classification of the cells that compose a tissue or an organ is key to understanding how these cells cooperate and interact as a functional unit. Our... (Review)
Review
The systematic classification of the cells that compose a tissue or an organ is key to understanding how these cells cooperate and interact as a functional unit. Our capacity to detect features that define cell identity has evolved from morphological and chemical analyses, through the use of predefined genetic markers, to unbiased transcriptomic and epigenetic profiling. The innovative technology of single-cell RNA sequencing (scRNA-seq) enables transcriptional profiling of thousands of individual cells. Since its development, scRNA-seq has been extensively applied to numerous organs and tissues in a wide range of animal models and human samples, thereby providing a plethora of fundamental biological insights into their development, homeostasis, and pathology. In this review, we present the findings of 3 recent studies that employed scRNA-seq to unravel the complexity of cellular composition in mammalian teeth. These findings offer an unprecedented catalogue of cell types in the mouse incisor, which is a convenient model system for studying continuous tooth growth. These studies identified novel cell types in the tooth epithelium and mesenchyme, as well as new markers for known cell types. Computational analyses of the data also uncovered the lineage and dynamics of cell states during ameloblast and odontoblast differentiation during both normal homeostasis and injury repair. The transcriptional differences between the mouse incisor and mouse and human molars uncover species-specific as well as shared features in tooth cell composition. Here, we highlight these findings and discuss important similarities and differences between these studies. We also discuss potential future applications of scRNA-seq in dental research and dentistry. Together, these studies demonstrate how the rapidly evolving technology of scRNA-seq can advance the study of tooth development and function and provide putative targets for regenerative approaches.
Topics: Animals; Cell Differentiation; Gene Expression Profiling; Genetic Markers; Mice; Sequence Analysis, RNA; Single-Cell Analysis; Transcriptome
PubMed: 33764175
DOI: 10.1177/00220345211001848 -
Frontiers in Physiology 2022Junctional epithelium (JE) is a vital epithelial component which forms an attachment to the tooth surface at the gingival sulcus by the adhesion of protein complexes... (Review)
Review
Junctional epithelium (JE) is a vital epithelial component which forms an attachment to the tooth surface at the gingival sulcus by the adhesion of protein complexes from its basal layer. Disruption of the JE is associated with the development of gingivitis, periodontal disease, and alveolar bone loss. Odontogenic ameloblast-associated (ODAM) is comprised of a signal peptide and an ODAM protein with 12 putative glycosylation sites. It is expressed during odontogenesis by maturation stage ameloblasts and is incorporated into the enamel matrix during the formation of outer and surface layer enamel. ODAM, as a secreted protein which is accumulated at the interface between basal lamina and enamel, mediates the adhesion of the JE to the tooth surface; and is involved with extracellular signalling of WNT and ARHGEF5-RhoA, as well as intracellular signalling of BMP-2-BMPR-IB-ODAM. ODAM is also found to be highly expressed in salivary glands and appears to have implications for the regulation of formation, repair, and regeneration of the JE. Bioinformatics and research data have identified the anti-cancer properties of ODAM, indicating its potential both as a prognostic biomarker and therapeutic target. Understanding the biology of ODAM will help to design therapeutic strategies for periodontal and dental disorders.
PubMed: 36117697
DOI: 10.3389/fphys.2022.1003931 -
International Journal of Molecular... Apr 2023Heat shock proteins (HSPs) are a class of molecular chaperones with expression increased in response to heat or other stresses. HSPs regulate cell homeostasis by... (Review)
Review
Heat shock proteins (HSPs) are a class of molecular chaperones with expression increased in response to heat or other stresses. HSPs regulate cell homeostasis by modulating the folding and maturation of intracellular proteins. Tooth development is a complex process that involves many cell activities. During tooth preparation or trauma, teeth can be damaged. The damaged teeth start their repair process by remineralizing and regenerating tissue. During tooth development and injury repair, different HSPs have different expression patterns and play a special role in odontoblast differentiation and ameloblast secretion by mediating signaling pathways or participating in protein transport. This review explores the expression patterns and potential mechanisms of HSPs, particularly HSP25, HSP60 and HSP70, in tooth development and injury repair.
Topics: Heat-Shock Proteins; Molecular Chaperones; HSP70 Heat-Shock Proteins; Odontogenesis; HSP90 Heat-Shock Proteins
PubMed: 37108621
DOI: 10.3390/ijms24087455