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International Journal of Oral Science Mar 2023Tooth germ injury can lead to abnormal tooth development and even tooth loss, affecting various aspects of the stomatognathic system including form, function, and...
Tooth germ injury can lead to abnormal tooth development and even tooth loss, affecting various aspects of the stomatognathic system including form, function, and appearance. However, the research about tooth germ injury model on cellular and molecule mechanism of tooth germ repair is still very limited. Therefore, it is of great importance for the prevention and treatment of tooth germ injury to study the important mechanism of tooth germ repair by a tooth germ injury model. Here, we constructed a Tg(dlx2b:Dendra2-NTR) transgenic line that labeled tooth germ specifically. Taking advantage of the NTR/Mtz system, the dlx2b tooth germ cells were depleted by Mtz effectively. The process of tooth germ repair was evaluated by antibody staining, in situ hybridization, EdU staining and alizarin red staining. The severely injured tooth germ was repaired in several days after Mtz treatment was stopped. In the early stage of tooth germ repair, the expression of phosphorylated 4E-BP1 was increased, indicating that mTORC1 is activated. Inhibition of mTORC1 signaling in vitro or knockdown of mTORC1 signaling in vivo could inhibit the repair of injured tooth germ. Normally, mouse incisors were repaired after damage, but inhibition/promotion of mTORC1 signaling inhibited/promoted this repair progress. Overall, we are the first to construct a stable and repeatable repair model of severe tooth germ injury, and our results reveal that mTORC1 signaling plays a crucial role during tooth germ repair, providing a potential target for clinical treatment of tooth germ injury.
Topics: Animals; Mice; Mechanistic Target of Rapamycin Complex 1; Signal Transduction; Tooth; Tooth Germ; Odontogenesis
PubMed: 36927863
DOI: 10.1038/s41368-023-00218-3 -
International Journal of Molecular... Feb 2023The activation of Wnt/β-catenin signalling is a prerequisite for odontogenesis. APC, a member of the AXIN-CK1-GSK3β-APC β-catenin destruction complex, functions to...
The activation of Wnt/β-catenin signalling is a prerequisite for odontogenesis. APC, a member of the AXIN-CK1-GSK3β-APC β-catenin destruction complex, functions to modulate Wnt/β-catenin signalling to establish regular teeth number and positions. APC loss-of-function mutations are associated with the over-activation of WNT/β-catenin signalling and subsequent familial adenomatous polyposis (FAP; MIM 175100) with or without multiple supernumerary teeth. The ablation of Apc function in mice also results in the constitutive activation of β-catenin in embryonic mouse epithelium and causes supernumerary tooth formation. The objective of this study was to investigate if genetic variants in the gene were associated with supernumerary tooth phenotypes. We clinically, radiographically, and molecularly investigated 120 Thai patients with mesiodentes or isolated supernumerary teeth. Whole exome and Sanger sequencing identified three extremely rare heterozygous variants (c.3374T>C, p.Val1125Ala; c.6127A>G, p.Ile2043Val; and c.8383G>A, p.Ala2795Thr) in in four patients with mesiodentes or a supernumerary premolar. An additional patient with mesiodens was compound as heterozygous for two variants (c.2740T>G, p.Cys914Gly, and c.5722A>T, p.Asn1908Tyr). Rare variants in in our patients are likely to contribute to isolated supernumerary dental phenotypes including isolated mesiodens and an isolated supernumerary tooth.
Topics: Animals; Humans; Mice; Adenomatous Polyposis Coli; Adenomatous Polyposis Coli Protein; beta Catenin; Genes, APC; Tooth, Supernumerary
PubMed: 36901686
DOI: 10.3390/ijms24054255 -
International Journal of Clinical... 2022Teeth are hard mineralized anatomical components of the dentofacial skeleton that are developed during the gestation period by odontogenesis. This dental development...
BACKGROUND
Teeth are hard mineralized anatomical components of the dentofacial skeleton that are developed during the gestation period by odontogenesis. This dental development comprises five stages initiation, proliferation, histodifferentiation, morphodifferentiation, and apposition. Excitation to the dental organ during morphodifferentiation is responsible for the formation of a talon cusp, which manifests as a cusp-like structure of hard tissue projecting from the cingulum to a varying measurable length toward the incisal edge of maxillary and mandibular anterior teeth. Various literature has reported that it comprises enamel, dentine, and an inconsistent amount of pulp tissue. Old literature suggests its occurrence in primary and permanent teeth and mostly on the palatal aspect of teeth as one cusp; therefore, known as a talon cusp (eagle's talon).
CASE DESCRIPTION
An exceptional case of three cusped structures projecting from the palatal side of a maxillary central incisor is thus reported. The rare occurrence of an atypical talon cusp with three well-defined mamelon-like cusps on the palatal surface of the permanent maxillary central incisor is coined as ternion cusp, meaning "three" by authors. Its occurrence is repercussed as attrition of the teeth in the opposite arch. Selective or retruded contact position (RCP) was done, followed by topical fluoride application was rendered.
CONCLUSION
Managing and treating these exceptional cusps depends upon their size, present complications, and patient compliance.
HOW TO CITE THIS ARTICLE
Sharma V, Mohapatra A, Bagchi A. Ternion Cusp: An Unusual Variant of Talon's Cusp: A Case Report. Int J Clin Pediatr Dent 2022;15(6):784-788.
PubMed: 36866150
DOI: 10.5005/jp-journals-10005-2476 -
NPJ Regenerative Medicine Feb 2023Maxillofacial hard tissue defects caused by trauma or infection often affect craniofacial function. Taking the natural hard tissue structure as a template, constructing...
Maxillofacial hard tissue defects caused by trauma or infection often affect craniofacial function. Taking the natural hard tissue structure as a template, constructing an engineered tissue repair module is an important scheme to realize the functional regeneration and repair of maxillofacial hard tissue. Here, inspired by the biomineralization process, we constructed a composite mineral matrix hydrogel PAA-CMC-TDM containing amorphous calcium phosphates (ACPs), polyacrylic acid (PAA), carboxymethyl chitosan (CMC) and dentin matrix (TDM). The dynamic network composed of Ca·COO coordination and ACPs made the hydrogel loaded with TDM, and exhibited self-repairing ability and injectability. The mechanical properties of PAA-CMC-TDM can be regulated, but the functional activity of TDM remains unaffected. Cytological studies and animal models of hard tissue defects show that the hydrogel can promote the odontogenesis or osteogenic differentiation of mesenchymal stem cells, adapt to irregular hard tissue defects, and promote in situ regeneration of defective tooth and bone tissues. In summary, this paper shows that the injectable TDM hydrogel based on biomimetic mineralization theory can induce hard tissue formation and promote dentin/bone regeneration.
PubMed: 36841873
DOI: 10.1038/s41536-023-00286-3 -
Genes Jan 2023WNT molecules are the regulators of various biological functions, including body axis formation, organ development, and cell proliferation and differentiation. WNTs have...
WNT molecules are the regulators of various biological functions, including body axis formation, organ development, and cell proliferation and differentiation. WNTs have been extensively studied as causative genes for an array of diseases. and , which are considered to be genes of the same origin, have been identified as causative genes for tooth deficiency in humans. However, the disrupted mutant of each gene does not show a decrease in teeth number. A negative feedback loop, interacting with several ligands based on a reaction-diffusion mechanism, was proposed to be important for the spatial patterning of tooth formation, and WNT ligands have been considered to play a pivotal role in controlling tooth patterning from mutant phenotypes of LDL receptor-related proteins (LRPs) and WNT co-receptors. The and double-mutants demonstrated severe root or enamel hypoplasia. In and mice, changes in the feedback loop may collapse the modulation of fusion or split a sequence of tooth formation. However, in the double-knockout mutant, a decrease in the number of teeth was observed, including the upper incisor or third molar in both jaws. These findings suggest that there may be a functional redundancy between and and that the interaction between the two genes functions in conjunction with other ligands to control the spatial patterning and development of teeth.
Topics: Animals; Humans; Mice; Cell Proliferation; Mutation; Nerve Tissue Proteins; Odontogenesis; Phenotype; Proto-Oncogene Proteins; Tooth; Wnt Proteins
PubMed: 36833267
DOI: 10.3390/genes14020340 -
BioMed Research International 2023Hard tissues make up the vast majority of teeth and are mineralized from the surrounding matrix. If the development of tooth germ is affected during mineralization,...
Transcriptomic Network Regulation of Rat Tooth Germ from Bell Differentiation Stage to Secretory Stage: MAPK Signaling Pathway Is Crucial to Extracellular Matrix Remodeling.
Hard tissues make up the vast majority of teeth and are mineralized from the surrounding matrix. If the development of tooth germ is affected during mineralization, hypoplasia of the tooth tissue can occur. To better understand the mechanisms mediating hypoplasia, we need to first study normal development. Using a rodent model, we highlight the transcriptomic changes that occur from the differentiation to secretion stages of mandibular molar germs. The tooth germ was dissected from rats at postnatal day 1.5 or 3.5 for high-throughput sequencing. Combining transcriptome analysis and DNA methylation, we identified 590 differentially expressed genes (436 upregulated and 154 downregulated) and 551 differentially expressed lncRNAs (long noncoding RNA; 369 upregulated and 182 downregulated) which were linked to the biological processes of odontogenesis, amelogenesis, tooth mineralization, and the alteration of extracellular matrix (ECM), especially matrix metalloproteinases (MMPs) and elastin. We found DNA methylation changes in 32 selected fragments involved in 5 chromosomes, 26 targets, and 2 haplotypes. Finally, three novel genes were identified: MMP20, Tgfb3, and Dusp1. Further analysis revealed that MMP20 has a role in odontogenesis and amelogenesis by influencing Slc24a4 and DSPP; Tgfb3 is involved in epithelial cell proliferation, cellular component disassembly process, ECM cellular component, and decomposition of cell components. But lncRNA expression could affect DNA methylation and mRNA expression. Moreover, the degree of DNA methylation could also affect the transcriptome level. Thus, Tgfb3 had no difference in DNA methylation, and Dusp1 conferred no difference at the transcriptome level. These three genes were all enriched in the MAPK pathway and played an important role in ECM remodeling. These data suggest that during the period of the bell differentiation stage to the secretory stage, along with enamel/dentin matrix secretion and hard tissue occurrence, the ECM is remodeled via MAPK signaling.
Topics: Rats; Animals; Transcriptome; Transforming Growth Factor beta3; Matrix Metalloproteinase 20; Tooth Germ; Odontogenesis; Cell Differentiation; Extracellular Matrix; Gene Expression Profiling; Signal Transduction
PubMed: 36820224
DOI: 10.1155/2023/4038278 -
Case Reports in Genetics 2023We encountered a case with congenital iris coloboma, omphalocele, and developmental delay with a 2.5 Mb deletion on chromosome 4q25 encompassing , leading to...
We encountered a case with congenital iris coloboma, omphalocele, and developmental delay with a 2.5 Mb deletion on chromosome 4q25 encompassing , leading to Axenfeld-Rieger syndrome (ARS), and . ARS is characterized by the aplasia of the anterior eye, odontogenesis, and abdominal wall aplasia. In our case, iris coloboma and omphalocele were thought to be caused by haploinsufficiency. However, these symptoms are nonspecific, and clinical symptoms alone can make it difficult to make a correct diagnosis. In addition, the genes responsible for developmental delay, among others, are not well understood. Developmental delay, in this case, might be caused due to haploinsufficiency. In spite of the partial deletion of , the causative gene of long QT syndrome type 4, the electrocardiogram was normal. Genetic testing can lead to a correct diagnosis, and it may be effective in detecting complications.
PubMed: 36816813
DOI: 10.1155/2023/4592114 -
Frontiers in Physiology 2022() plays important roles in both shaping the developing tooth and establishing the number of teeth within the tooth row. () has been shown to act downstream of and is...
() plays important roles in both shaping the developing tooth and establishing the number of teeth within the tooth row. () has been shown to act downstream of and is involved in the initiation of tooth development. mice possess hypoplastic and hypomineralized incisors and show changes in tooth number in the molar region. In the present study we used 3D reconstruction combined with expression analysis, cell lineage tracing experiments, and western blot analysis in order to investigate the formation of the incisor germs in mice. We show that a lack of functional Eda protein during early stages of incisor tooth germ development had minimal impact on development of the early expression of Shh in the incisor, a region proposed to mark formation of a rudimental incisor placode and act as an initiating signalling centre. In contrast, deficiency of Eda protein had a later impact on expression of in the primary enamel knot of the functional tooth. mice had a smaller region where was expressed, and a reduced contribution from Shh descendant cells. The reduction in the enamel knot led to the formation of an abnormal enamel organ creating a hypoplastic functional incisor. therefore appears to influence the spatial formation of the successional signalling centres during odontogenesis.
PubMed: 36699680
DOI: 10.3389/fphys.2022.1033130 -
Frontiers in Physiology 2022During tooth development, proper protein folding and trafficking are significant processes as newly synthesized proteins proceed to form designated tissues. Endoplasmic...
During tooth development, proper protein folding and trafficking are significant processes as newly synthesized proteins proceed to form designated tissues. Endoplasmic reticulum (ER) stress occurs inevitably in tooth development as unfolded and misfolded proteins accumulate in ER. 4-Phenylbutyric acid (4PBA) is a FDA approved drug and known as a chemical chaperone which alleviates the ER stress. Recently, several studies showed that 4PBA performs therapeutic effects in some genetic diseases due to misfolding of proteins, metabolic related-diseases and apoptosis due to ER stress. However, the roles of 4PBA during odontogenesis are not elucidated. This study revealed the effects of 4PBA during molar development in mice. We employed in vitro organ cultivation and renal transplantation methods which would mimic the permanent tooth development in an infant period of human. The cultivated tooth germs and renal calcified teeth were examined by histology and immunohistochemical analysis. Our results revealed that treatment of 4PBA altered expression patterns of enamel knot related signaling molecules, and consequently affected cellular secretion and patterned formation of dental hard tissues including dentin and enamel during tooth morphogenesis. The alteration of ER stress by 4PBA treatment during organogenesis would suggest that proper ER stress is important for pattern formation during tooth development and morphogenesis, and 4PBA as a chemical chaperone would be one of the candidate molecules for dental and hard tissue regeneration.
PubMed: 36685173
DOI: 10.3389/fphys.2022.1079355 -
Biomolecules Jan 2023The regeneration of periodontal tissues is a decisive factor in the treatment of periodontitis. Currently, to achieve complete periodontal regeneration, many studies...
The regeneration of periodontal tissues is a decisive factor in the treatment of periodontitis. Currently, to achieve complete periodontal regeneration, many studies have evaluated the effectiveness of decellularized tissue-engineered constructs on periodontal regeneration. We studied the possibilities of osteogenic and odontogenic differentiation of periodontal progenitor and stem cells (SCs) of the periosteum and periodontal ligament, in decellularized tooth matrix (dTM) and periodontal ligament (dPDL), in 2D and 3D culture. The cell culture of periodontal cells without decellularized matrices was used as control. On the 14th day of cultivation of PDLSCs, PSCs, and PDLSCs + PSCs on dTM and/or dPDL scaffolds in 2D conditions, in all scaffold variants, a dense monolayer of spindle-shaped cells was intensely stained for markers of osteogenic differentiation, such as osteopontin and osteocalcin. Periodontal cells in the collagen I hydrogel (3D-dimensional culture) were more diverse in shape and, in combination of dTM and dPDL, in addition to osteogenic expression, expressed dentin sialophosphoprotein, an odontogenic differentiation marker. Thus, collagen I hydrogel contributed to the formation of conditions similar to those in vivo, and the combination of dTM with dPDL apparently formed a microenvironment that promoted osteogenic and odontogenic differentiation of periodontal cells.
Topics: Osteogenesis; Cell Differentiation; Stem Cells; Cells, Cultured; Collagen Type I; Hydrogels; Cell Proliferation
PubMed: 36671506
DOI: 10.3390/biom13010122