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Nature Reviews. Endocrinology Jun 2021The major mineralized tissues are bone and teeth, which share several mechanisms governing their development and mineralization. This crossover includes the hormones... (Review)
Review
The major mineralized tissues are bone and teeth, which share several mechanisms governing their development and mineralization. This crossover includes the hormones that regulate circulating calcium and phosphate concentrations, and the genes that regulate the differentiation and transdifferentiation of cells. In developing endochondral bone and in developing teeth, parathyroid hormone-related protein (PTHrP) acts in chondrocytes to delay terminal differentiation, thereby increasing the pool of precursor cells. Chondrocytes and (in specific circumstances) pre-odontoblasts can also transdifferentiate into osteoblasts. Moreover, bone and teeth share outcomes when affected by systemic disorders of mineral homeostasis or of the extracellular matrix, and by adverse effects of treatments such as bisphosphonates and fluoride. Unlike bone, teeth have more permanent effects from systemic disorders because they are not remodelled after they are formed. This Review discusses the normal processes of bone and tooth development, followed by disorders that have effects on both bone and teeth, versus disorders that have effects in one without affecting the other. The takeaway message is that bone specialists should know when to screen for dental disorders, just as dental specialists should recognize when a tooth disorder should raise suspicions about a possible underlying bone disorder.
Topics: Animals; Biomineralization; Bone Development; Bone Diseases, Developmental; Humans; Odontogenesis; Tooth Diseases
PubMed: 33948016
DOI: 10.1038/s41574-021-00488-z -
International Journal of Molecular... Nov 2022The tooth-periodontium complex and its nerves have active reciprocal regulation during development and homeostasis. These effects are predominantly mediated by a range... (Review)
Review
The tooth-periodontium complex and its nerves have active reciprocal regulation during development and homeostasis. These effects are predominantly mediated by a range of molecules secreted from either the nervous system or the tooth-periodontium complex. Different strategies mimicking tooth development or physiological reparation have been applied to tooth regeneration studies, where the application of these nerve- or tooth-derived molecules has been proven effective. However, to date, basic studies in this field leave many vacancies to be filled. This literature review summarizes the recent advances in the basic studies on neural responses and regulation during tooth-periodontium development and homeostasis and points out some research gaps to instruct future studies. Deepening our understanding of the underlying mechanisms of tooth development and diseases will provide more clues for tooth regeneration.
Topics: Odontogenesis; Periodontal Ligament; Tooth; Periodontium; Homeostasis
PubMed: 36430624
DOI: 10.3390/ijms232214150 -
Stem Cells (Dayton, Ohio) Jan 2019Development of teeth depends on the reciprocal interactions between the surface epithelium (ectoderm) and the underlying neural crest-derived mesenchyme. These... (Review)
Review
Development of teeth depends on the reciprocal interactions between the surface epithelium (ectoderm) and the underlying neural crest-derived mesenchyme. These interactions are facilitated by the conserved signaling pathways, which build a complex network of signals and transcription factors. Tooth development starts at specific and predetermined loci in the oral ectoderm and is described as a morphologically distinct thickening of oral ectoderm, named dental lamina. Cells within the dental lamina invaginate into the underlying mesenchyme, generating placodes that mark the onset of individual tooth development. In the following stages of development, the tooth epithelium buds and folds transitioning through various shapes, including bud, cap, and bell shapes, which also identify the specific stages of tooth development. Although much of the molecular regulation of tooth development has been unraveled, the regulation of the initial stages of tooth development, as well as the cellular mechanisms that govern tooth development remain largely unknown. This review provides a systematic overview of the current knowledge on the molecular and cellular mechanisms that guide initial stages of tooth development and outlines the challenges which temper the progress. Stem Cells 2019;37:26-32.
Topics: Cell Biology; Humans; Odontogenesis; Tooth
PubMed: 30270477
DOI: 10.1002/stem.2917 -
Journal of Dental Research Nov 2016Primary cilia, present on most mammalian cells, function as a sensor to sense the environment change and transduce signaling. Loss of primary cilia causes a group of... (Review)
Review
Primary cilia, present on most mammalian cells, function as a sensor to sense the environment change and transduce signaling. Loss of primary cilia causes a group of human pleiotropic syndromes called Ciliopathies. Some of the ciliopathies display skeletal dysplasias, implying the important role of primary cilia in skeletal development and homeostasis. Emerging evidence has shown that loss or malfunction of primary cilia or ciliary proteins in bone and cartilage is associated with developmental and function defects. Intraflagellar transport (IFT) proteins are essential for cilia formation and/or function. In this review, we discuss the role of primary cilia and IFT proteins in the development of bone and cartilage, as well as the differentiation and mechanotransduction of mesenchymal stem cells, osteoblasts, osteocytes, and chondrocytes. We also include the role of primary cilia in tooth development and highlight the current advance of primary cilia and IFT proteins in the pathogenesis of cartilage diseases, including osteoarthritis, osteosarcoma, and chondrosarcoma.
Topics: Animals; Bone Diseases; Carrier Proteins; Cartilage; Cartilage Diseases; Cell Differentiation; Cilia; Flagella; Humans; Mechanotransduction, Cellular; Odontogenesis; Osteogenesis; Protein Transport
PubMed: 27250654
DOI: 10.1177/0022034516652383 -
Gene Jan 2017MicroRNAs (miRNAs) are a class of small, non-coding RNAs that provide an efficient pathway for regulation of gene expression at a post-transcriptional level. Tooth... (Review)
Review
MicroRNAs (miRNAs) are a class of small, non-coding RNAs that provide an efficient pathway for regulation of gene expression at a post-transcriptional level. Tooth development is regulated by a complex network of cell-cell signaling during all steps of organogenesis. Most of the congenital dental defects in humans are caused by mutations in genes involved in developmental regulatory networks. Whereas the developmental morphological stages of the tooth development already are thoroughly documented, the implicated genetic network is still under investigation. The involvement of miRNAs in the regulation of tooth genetic network was suggested for the first time in 2008. MiRNAs regulate tooth morphogenesis by fine-tuning the signaling networks. Unique groups of miRNAs are expressed in dental epithelium compared with mesenchyme, as well as in molars compared with incisors. The present review focuses on the current state of knowledge on the expression and function of miRNAs in human dental tissues, including teeth and the surrounding structures. Herein, we show that miRNAs exhibit specific roles in human dental tissues and are involved in gingival and periodontal disease, tooth movement and eruption, dental pulp physiology including repair and regeneration, differentiation of dental cells, and enamel mineralization. In light of similarities between the tooth development and other organs originating from the epithelium, further understanding of miRNAs` function in dental tissues may have wide biological relevance.
Topics: Dental Enamel; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Gingival Diseases; Humans; MicroRNAs; Odontogenesis; Periodontal Diseases; Pulpitis; Tooth; Tooth Eruption
PubMed: 27725267
DOI: 10.1016/j.gene.2016.10.009 -
Medicina Oral, Patologia Oral Y Cirugia... May 2020The primordial odontogenic tumor (POT) is a recently described benign entity with histopathological and immunohistochemical features suggesting its origin during early...
BACKGROUND
The primordial odontogenic tumor (POT) is a recently described benign entity with histopathological and immunohistochemical features suggesting its origin during early odontogenesis.
AIM
To integrate the available data published on POT into a comprehensive analysis to better define its clinicopathological and molecular features.
MATERIAL AND METHODS
An electronic systematic review was performed up to September 2019 in multiple databases.
RESULTS
A total of 13 publications were included, representing 16 reported cases and 3 molecular studies. The mean age of the affected patients was 11.6 years (range 2-19), with a slight predominance in males (56.25%). The posterior mandible was the main location (87.5%), with only two cases affecting the posterior maxilla. All cases appeared as a radiolucent lesion in close relationship to an unerupted tooth. Recurrences have not been reported to date. Microscopically, POT comprises fibromyxoid tissue with variable cellularity surrounded by a cuboidal to columnar odontogenic epithelium but without unequivocal dental hard tissue formation. A delicate fibrous capsule surrounds (at least partially) the tumor. The epithelial component shows immunohistochemical positivity for amelogenin, CK19, and CK14, and variable expression of Glut-1, Galectin-3 and Caveolin-1, Vimentin, p-53, PITX2, Bcl-2, Bax and Survivin; the mesenchymal tissue is positive for Vimentin, CD90, p-53, PITX2, Bcl-2, Bax, and Survivin, and the subepithelial region exhibits the strong expression of Syndecan-1 and CD34. The Ki-67 index is low (<5%). The negative or weak expression of dentinogenesis-associated genes could explain the inhibition of dentin and subsequent enamel formation in this neoplasm.
CONCLUSION
POT is an entity with a well-defined clinicopathological, immunohistochemical and molecular profile that must be properly diagnosed and differentiated from other odontogenic lesions and treated consequently.
Topics: Adolescent; Adult; Child; Child, Preschool; Epithelium; Humans; Male; Mandible; Neoplasm Recurrence, Local; Odontogenesis; Odontogenic Tumors; Young Adult
PubMed: 32040459
DOI: 10.4317/medoral.23432 -
Science Bulletin Jun 2022The spatiotemporal relationships in high-resolution during odontogenesis remain poorly understood. We report a cell lineage and atlas of developing mouse teeth. We...
The spatiotemporal relationships in high-resolution during odontogenesis remain poorly understood. We report a cell lineage and atlas of developing mouse teeth. We performed a large-scale (92,688 cells) single cell RNA sequencing, tracing the cell trajectories during odontogenesis from embryonic days 10.5 to 16.5. Combined with an assay for transposase-accessible chromatin with high-throughput sequencing, our results suggest that mesenchymal cells show the specific transcriptome profiles to distinguish the tooth types. Subsequently, we identified key gene regulatory networks in teeth and bone formation and uncovered spatiotemporal patterns of odontogenic mesenchymal cells. CD24 and Plac8 cells from the mesenchyme at the bell stage were distributed in the upper half and preodontoblast layer of the dental papilla, respectively, which could individually induce nonodontogenic epithelia to form tooth-like structures. Specifically, the Plac8 tissue we discovered is the smallest piece with the most homogenous cells that could induce tooth regeneration to date. Our work reveals previously unknown heterogeneity and spatiotemporal patterns of tooth germs that may lead to tooth regeneration for regenerative dentistry.
Topics: Mice; Animals; Odontogenesis; Tooth; Tooth Germ; Mesenchymal Stem Cells; Epithelium
PubMed: 36545982
DOI: 10.1016/j.scib.2022.03.012 -
Stomatologiia 2016
Review
Topics: Calcification, Physiologic; Dental Enamel; Humans; Odontogenesis; Tooth
PubMed: 27441320
DOI: 10.17116/stomat201695279-783 -
Journal of Dental Research Jul 2023The enamel knot (EK), located at the center of cap stage tooth germs, is a transitory cluster of nondividing epithelial cells. The EK acts as a signaling center that...
The enamel knot (EK), located at the center of cap stage tooth germs, is a transitory cluster of nondividing epithelial cells. The EK acts as a signaling center that provides positional information for tooth morphogenesis and regulates the growth of tooth cusps. To identify species-specific cuspal patterns, this study analyzed the cellular mechanisms in the EK that were related to bone morphogenetic protein (Bmp), which plays a crucial role in cell proliferation and apoptosis. To understand the cellular mechanisms in the EK, the differences between 2 species showing different cuspal patterning, mouse (pointy bunodont cusp) and gerbil (flat lophodont cusp), were analyzed with quantitative reverse transcriptase polymerase chain reaction and immunofluorescent staining. Based on these, we performed protein-soaked bead implantation on tooth germs of the 2 different EK regions and compared the cellular behavior in the EKs of the 2 species. Many genes related with cell cycle, cell apoptosis, and cell proliferation were involved in BMP signaling in the EK during tooth development. A comparison of the cell proliferation and apoptosis associated with Bmp revealed distinctive patterns of the cellular mechanisms. Our findings indicate that the cellular mechanisms, such as cell proliferation and apoptosis, in the EK are related to Bmp4 and play an important role in tooth morphogenesis.
Topics: Animals; Mice; Tooth; Dental Enamel; Odontogenesis; Tooth Germ; Bone Morphogenetic Proteins; Cell Proliferation; Apoptosis; Bone Morphogenetic Protein 4
PubMed: 37246809
DOI: 10.1177/00220345231167769 -
Oral Diseases Nov 2022Nuclear factor I-C (NFIC) plays a critical role in regulating epithelial-mesenchymal crosstalk during tooth development. However, it remains largely unknown about how... (Review)
Review
OBJECTIVES
Nuclear factor I-C (NFIC) plays a critical role in regulating epithelial-mesenchymal crosstalk during tooth development. However, it remains largely unknown about how NFIC functions in dentin and enamel formation. In the present review, we aim to summarize the most recent discoveries in the field and gain a better understanding of the roles NFIC performs during tooth formation.
SUBJECTS AND METHODS
Nfic mice exhibit human dentin dysplasia type I (DDI)-like phenotypes signified by enlarged pulp chambers, the presence of short-root anomaly, and failure of odontoblast differentiation. Although loss of NFIC has little effect on molar crown morphology, researchers have detected aberrant microstructures of enamel in the incisors. Recently, accumulating evidence has further uncovered the novel function of NFIC in the process of enamel and dentin formation.
RESULTS
During epithelial-mesenchyme crosstalk, the expression of NFIC is under the control of SHH-PTCH-SMO-GLI1 pathway. NFIC is closely involved in odontoblast lineage cells proliferation and differentiation, and the maintenance of NFIC protein level in cytoplasm is negatively regulated by TGF-β signaling pathway. In addition, NFIC has mild effect on ameloblast differentiation, enamel mineralization and cementum formation.
CONCLUSIONS
NFIC plays an important role in tooth development and is required for the formation of dentin, enamel as well as cementum.
Topics: Animals; Cell Differentiation; Humans; Mice; NFI Transcription Factors; Odontoblasts; Odontogenesis; Tooth Root; Transforming Growth Factor beta; Zinc Finger Protein GLI1
PubMed: 34637578
DOI: 10.1111/odi.14046