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Journal of Dental Research Oct 2023In humans, teeth are replaced only once, and the successional dental lamina (SDL) of the permanent tooth is maintained in a quiescent state until adolescence. Recently,...
In humans, teeth are replaced only once, and the successional dental lamina (SDL) of the permanent tooth is maintained in a quiescent state until adolescence. Recently, we showed that biomechanical stress generated by the rapid growth of the deciduous tooth inhibits SDL development via integrin β1-RUNX2 signaling at embryonic day 60 (E60) in miniature pigs. However, the mechanism by which RUNX2 regulates SDL initiation within the SDL stem cell niche remains unclear. In the current study, we transcriptionally profiled single cells from SDL and surrounding mesenchyme at E60 and identified the landscape of cellular heterogeneity. We then identified a specific fibroblast subtype in the dental follicle mesenchyme between the deciduous tooth and the SDL of the permanent tooth (DFDP), which constitutes the inner part of the niche (deciduous tooth side). Compared with traditional dental follicle cells, the specific expression profile of DFDP was identified and found to be related to biomechanical stress. Subsequently, we found that RUNX2 could bind to the enhancer regions of (gene of fibulin-1), one of the marker genes for DFDP. Through gain- and loss-of-function experiments, we proved that the biomechanical stress-mediated RUNX2-fibulin-1 axis inhibits the initiation of SDL by maintaining SDL niche homeostasis.
Topics: Animals; Core Binding Factor Alpha 1 Subunit; Dentition, Permanent; Odontogenesis; Swine; Tooth
PubMed: 37448354
DOI: 10.1177/00220345231182052 -
International Journal of Oral Science Nov 2023Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation. The initiation of Hertwig's epithelial root sheath (HERS) induces... (Review)
Review
Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation. The initiation of Hertwig's epithelial root sheath (HERS) induces odontoblast differentiation and the subsequent radicular dentin deposition. Precisely controlled signaling pathways modulate the behaviors of HERS and the fates of dental mesenchymal stem cells (DMSCs). Disruptions in these pathways lead to defects in root development, such as shortened roots and furcation abnormalities. Advances in dental stem cells, biomaterials, and bioprinting show immense promise for bioengineered tooth root regeneration. However, replicating the developmental intricacies of odontogenesis has not been resolved in clinical treatment and remains a major challenge in this field. Ongoing research focusing on the mechanisms of root development, advanced biomaterials, and manufacturing techniques will enable next-generation biological root regeneration that restores the physiological structure and function of the tooth root. This review summarizes recent discoveries in the underlying mechanisms governing root ontogeny and discusses some recent key findings in developing of new biologically based dental therapies.
Topics: Female; Humans; Tooth Root; Odontogenesis; Epithelial Cells; Cell Differentiation; Biocompatible Materials
PubMed: 38001110
DOI: 10.1038/s41368-023-00258-9 -
Zhonghua Kou Qiang Yi Xue Za Zhi =... Mar 2021Epigenetics refers to genetic regulation patterns that gene expressions, which lead to the phenotype variance, are modified in the absence of changes of DNA sequence.... (Review)
Review
Epigenetics refers to genetic regulation patterns that gene expressions, which lead to the phenotype variance, are modified in the absence of changes of DNA sequence. Epigenetics mainly includes DNA methylation, histone modification, and non-coding RNA regulation. During the development of the teeth, conventional gene regulation and epigenetics synergistically regulate the spatial and temporal expression of genes, which involved in cell proliferation, differentiation and finally the formation of teeth. Exploration of the epigenetic regulation mechanisms during tooth development can provide multiple clues and ideas for the research of tooth regeneration. This article reviewed the significant roles of epigenetic regulation in tooth development.
Topics: Cell Differentiation; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation; Odontogenesis
PubMed: 33663161
DOI: 10.3760/cma.j.cn112144-20200518-00283 -
Pathologie (Heidelberg, Germany) Aug 2022Odontogenic tumors (OTs) comprise a group of heterogeneous lesions ranging from hamartomatous or non-neoplastic tissue proliferation to benign or malignant neoplasms... (Review)
Review
BACKGROUND
Odontogenic tumors (OTs) comprise a group of heterogeneous lesions ranging from hamartomatous or non-neoplastic tissue proliferation to benign or malignant neoplasms with metastatic potential. OTs are derived from epithelial, ectomesenchymal, and/or mesenchymal elements of tooth-forming ("odontogenic") tissues, which show variable clinical and histopathological features.
OBJECTIVE
Herein, the authors summarize the World Health Organization (WHO) 2022 classification of OTs and further highlight diagnostic tips and differential clues for the most common OTs.
CONCLUSION
OTs may not be commonly encountered in the daily practice of many pathologists. This makes their diagnosis challenging as there is little practice in understanding the features required for their classification. However, diagnosing the vast majority of these lesions is not difficult provided the following aspects are considered: 1) the general knowledge of tooth development; 2) a few key histological observations; 3) very basic knowledge of the clinical and especially the radiographic features with which they are associated.
Topics: Humans; Odontogenic Tumors; Odontogenesis; Tooth; World Health Organization; Hamartoma
PubMed: 36346463
DOI: 10.1007/s00292-022-01150-9 -
Journal of Dental Research Jul 2015Mammalian tooth development is a precise and complicated procedure. Several signaling pathways, such as nuclear factor (NF)-κB and WNT, are key regulators of tooth... (Review)
Review
Mammalian tooth development is a precise and complicated procedure. Several signaling pathways, such as nuclear factor (NF)-κB and WNT, are key regulators of tooth development. Any disturbance of these signaling pathways can potentially affect or block normal tooth development, and presently, there are more than 150 syndromes and 80 genes known to be related to tooth agenesis. Clarifying the interaction and crosstalk among these genes will provide important information regarding the mechanisms underlying missing teeth. In the current review, we summarize recently published findings on genes related to isolated and syndromic tooth agenesis; most of these genes function as positive regulators of cell proliferation or negative regulators of cell differentiation and apoptosis. Furthermore, we explore the corresponding networks involving these genes in addition to their implications for the clinical management of tooth agenesis. We conclude that this requires further study to improve patients' quality of life in the future.
Topics: Anodontia; Apoptosis; Cell Differentiation; Cell Proliferation; Gene Regulatory Networks; Humans; Odontogenesis; Signal Transduction
PubMed: 25910507
DOI: 10.1177/0022034515583999 -
Journal of Dental Research Aug 2017Primary cilium is a solitary organelle that emanates from the surface of most postmitotic mammalian cells and serves as a sensory organelle, transmitting the mechanical... (Review)
Review
Primary cilium is a solitary organelle that emanates from the surface of most postmitotic mammalian cells and serves as a sensory organelle, transmitting the mechanical and chemical cues to the cell. Primary cilia are key coordinators of various signaling pathways during development and maintenance of tissue homeostasis. The emerging evidence implicates primary cilia function in tooth development. Primary cilia are located in the dental epithelium and mesenchyme at early stages of tooth development and later during cell differentiation and production of hard tissues. The cilia are present when interactions between both the epithelium and mesenchyme are required for normal morphogenesis. As the primary cilium coordinates several signaling pathways essential for odontogenesis, ciliary defects can interrupt the latter process. Genetic or experimental alterations of cilia function lead to various developmental defects, including supernumerary or missing teeth, enamel and dentin hypoplasia, or teeth crowding. Moreover, dental phenotypes are observed in ciliopathies, including Bardet-Biedl syndrome, Ellis-van Creveld syndrome, Weyers acrofacial dysostosis, cranioectodermal dysplasia, and oral-facial-digital syndrome, altogether demonstrating that primary cilia play a critical role in regulation of both the early odontogenesis and later differentiation of hard tissue-producing cells. Here, we summarize the current evidence for the localization of primary cilia in dental tissues and the impact of disrupted cilia signaling on tooth development in ciliopathies.
Topics: Animals; Cell Differentiation; Cilia; Humans; Maxillofacial Development; Odontogenesis; Signal Transduction
PubMed: 28605602
DOI: 10.1177/0022034517713688 -
Journal of Dental Research Apr 2024Tooth development and regeneration are regulated through a complex signaling network. Previous studies have focused on the exploration of intracellular signaling... (Review)
Review
Tooth development and regeneration are regulated through a complex signaling network. Previous studies have focused on the exploration of intracellular signaling regulatory networks, but the regulatory roles of extracellular networks have only been revealed recently. Proteoglycans, which are essential components of the extracellular matrix (ECM) and pivotal signaling molecules, are extensively involved in the process of odontogenesis. Proteoglycans are composed of core proteins and covalently attached glycosaminoglycan chains (GAGs). The core proteins exhibit spatiotemporal expression patterns during odontogenesis and are pivotal for dental tissue formation and periodontium development. Knockout of core protein genes , , , and has been shown to result in structural defects in enamel and dentin mineralization. They are also closely involved in the development and homeostasis of periodontium by regulating signaling transduction. As the functional component of proteoglycans, GAGs are negatively charged unbranched polysaccharides that consist of repeating disaccharides with various sulfation groups; they provide binding sites for cytokines and growth factors in regulating various cellular processes. In mice, GAG deficiency in dental epithelium leads to the reinitiation of tooth germ development and the formation of supernumerary incisors. Furthermore, GAGs are critical for the differentiation of dental stem cells. Inhibition of GAGs assembly hinders the differentiation of ameloblasts and odontoblasts. In summary, core proteins and GAGs are expressed distinctly and exert different functions at various stages of odontogenesis. Given their unique contributions in odontogenesis, this review summarizes the roles of proteoglycans and GAGs throughout the process of odontogenesis to provide a comprehensive understanding of tooth development.
Topics: Mice; Animals; Glycosaminoglycans; Mice, Knockout; Odontogenesis; Extracellular Matrix Proteins; Tooth Germ
PubMed: 38407002
DOI: 10.1177/00220345231224228 -
MicroRNA (Shariqah, United Arab... 2016MicroRNAs (miRNAs) are non-coding RNAs that are involved in various biological pathways by regulating gene expression. Teeth develop via reciprocal and sequential... (Review)
Review
MicroRNAs (miRNAs) are non-coding RNAs that are involved in various biological pathways by regulating gene expression. Teeth develop via reciprocal and sequential interactions between the epithelium and the ectomesenchyme. The speci.c functions of several genes during tooth development are known, and the involvement of their mutations in the pathogenesis of congenital dental defects has been widely studied. The miRNA pathway is considered to have a significant role in embryogenesis including tooth development. It has been shown that miRNAs regulate morphogenesis of tooth by fine-tuning the signalling networks, however, their precise role in tooth differentiation and morphogenesis is still elusive. The present review focuses on the studies that have used animal models to explore the function of miRNAs in tooth development. Major findings with special emphasis on the miRNA involvement in .ne-tuning and network regulation are presented and discussed. Disturbances in tooth development in the global miRNA processing knockouts mirror the essential fine-tuning guiding appropriate formation of dental hard tissues. However, further investigation of single miRNA function and mutation, including deletion and overexpression, may lead to improved knowledge on development of particular dental defects in humans. In the light of similarities between tooth development and other organs originating from the epithelium, further understanding of miRNAs` function during tooth development may have wide biological relevance.
Topics: Animals; Gene Expression Regulation, Developmental; Mice; MicroRNAs; Odontogenesis; Tooth
PubMed: 27397033
DOI: 10.2174/2211536605666160706003256 -
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 Orthodontics Jun 2015Cancers during infancy and childhood affect 1 to 3% of children under the age of 15. Among these cancers the most frequent are malignant hemopathies, and in particular,... (Review)
Review
Cancers during infancy and childhood affect 1 to 3% of children under the age of 15. Among these cancers the most frequent are malignant hemopathies, and in particular, acute lymphoblastic leukemia, which represents 80% of infant leukemias, with a peak of incidence around the age of 3-4. The overall prognosis for infant malignant hemopathies has improved significantly thanks to progress made in chemotherapy and radiotherapy. However, these anti-cancer treatments, particularly radiotherapy, when performed early, generally before 5 years of age, can have harmful effects that interfere with overall growth and particularly cranio-facial growth, and also with the child's oro-dental development. Some effects such as mandibular retrognathia, macrodontia, microdontia, agenesis and delayed eruption could increase the need for orthodontic treatment, while other complications, particularly the reduced height of the alveolar processes, short thin roots and modification of the superficial and profound periodontium, are likely to make such treatment more difficult. The aim of this review of the literature is to identify the essential factors that must be analyzed before orthodontic treatment is proposed for subjects who have undergone radiotherapy at an early age, and the precautions to be taken before and during orthodontic treatment.
Topics: Age Factors; Head; Hematologic Neoplasms; Humans; Malocclusion; Maxillofacial Development; Odontogenesis; Orthodontics, Corrective; Patient Care Planning
PubMed: 25986706
DOI: 10.1016/j.ortho.2015.03.017