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Developmental Cell Oct 2023Tooth enamel secreted by ameloblasts (AMs) is the hardest material in the human body, acting as a shield to protect the teeth. However, the enamel is gradually damaged...
Tooth enamel secreted by ameloblasts (AMs) is the hardest material in the human body, acting as a shield to protect the teeth. However, the enamel is gradually damaged or partially lost in over 90% of adults and cannot be regenerated due to a lack of ameloblasts in erupted teeth. Here, we use single-cell combinatorial indexing RNA sequencing (sci-RNA-seq) to establish a spatiotemporal single-cell census for the developing human tooth and identify regulatory mechanisms controlling the differentiation process of human ameloblasts. We identify key signaling pathways involved between the support cells and ameloblasts during fetal development and recapitulate those findings in human ameloblast in vitro differentiation from induced pluripotent stem cells (iPSCs). We furthermore develop a disease model of amelogenesis imperfecta in a three-dimensional (3D) organoid system and show AM maturation to mineralized structure in vivo. These studies pave the way for future regenerative dentistry.
Topics: Humans; Ameloblasts; Amelogenesis; Dental Enamel; Odontogenesis; Tooth
PubMed: 37582367
DOI: 10.1016/j.devcel.2023.07.013 -
Physiological Reviews Jul 2023The teeth are vertebrate-specific, highly specialized organs performing fundamental functions of mastication and speech, the maintenance of which is crucial for... (Review)
Review
The teeth are vertebrate-specific, highly specialized organs performing fundamental functions of mastication and speech, the maintenance of which is crucial for orofacial homeostasis and is further linked to systemic health and human psychosocial well-being. However, with limited ability for self-repair, the teeth can often be impaired by traumatic, inflammatory, and progressive insults, leading to high prevalence of tooth loss and defects worldwide. Regenerative medicine holds the promise to achieve physiological restoration of lost or damaged organs, and in particular an evolving framework of developmental engineering has pioneered functional tooth regeneration by harnessing the odontogenic program. As a key event of tooth morphogenesis, mesenchymal condensation dictates dental tissue formation and patterning through cellular self-organization and signaling interaction with the epithelium, which provides a representative to decipher organogenetic mechanisms and can be leveraged for regenerative purposes. In this review, we summarize how mesenchymal condensation spatiotemporally assembles from dental stem cells (DSCs) and sequentially mediates tooth development. We highlight condensation-mimetic engineering efforts and mechanisms based on ex vivo aggregation of DSCs, which have achieved functionally robust and physiologically relevant tooth regeneration after implantation in animals and in humans. The discussion of this aspect will add to the knowledge of development-inspired tissue engineering strategies and will offer benefits to propel clinical organ regeneration.
Topics: Tooth; Odontogenesis; Tissue Engineering; Humans; Animals; Mesoderm; Tooth Loss; Bone Regeneration
PubMed: 36656056
DOI: 10.1152/physrev.00019.2022 -
L' Orthodontie Francaise Nov 2023The precise diagnosis of dental structural anomalies is an essential step preceding our restorative and orthodontic therapies. Indeed, first of all, it is necessary to...
INTRODUCTION
The precise diagnosis of dental structural anomalies is an essential step preceding our restorative and orthodontic therapies. Indeed, first of all, it is necessary to identify the type of structural anomaly and to determine if it is an isolated or a syndromic form: the dental anomaly could be included in a more complex clinical picture combining other clinical signs. Moreover, the establishment of the diagnosis will allow the practitioner to adapt his clinical protocol according to the observed dental structure anomaly. The choice of the bonding material, the type of preparation (no prep, prep less, complete eviction), and the application of a deproteinization protocol with sodium hypochlorite depend to the structural defect.
MATERIAL AND METHOD
The diagnosis of dental structural anomalies is based on several key points described in this article in order to facilitate the practitioner's diagnostic approach.
CONCLUSION
The diagnosis of amelogenesis or dentinogenesis imperfecta should justify the search for other signs to determine whether the anomaly of tooth structure is isolated or syndromic.
Topics: Humans; Amelogenesis; Dental Materials; Sodium Hypochlorite
PubMed: 37930342
DOI: 10.1684/orthodfr.2023.134 -
Pediatric and Developmental Pathology :... 2023Evaluation of bone pathology within the head and neck region, particularly the gnathic bonesis is complex, demonstrating unique pathologic processes. In part, this... (Review)
Review
Evaluation of bone pathology within the head and neck region, particularly the gnathic bonesis is complex, demonstrating unique pathologic processes. In part, this variation is due to odontogenesis and the embryological cells that may be involved, which can contribute to disease development and histologic variability. As with any boney pathosis, the key is to have clinical correlation, particularly with radiographic imaging prior to establishing a definitive diagnosis. This review will cover those entities that have a predilection for the pediatric population, and while it is not all inclusive, it should serve as a foundation for the pathologist who is evaluating bony lesions involving the craniofacial skeleton.
Topics: Humans; Child; Bone and Bones; Neck; Neoplasms; Odontogenic Tumors
PubMed: 37232383
DOI: 10.1177/10935266231170744 -
Frontiers in Bioscience (Landmark... Oct 2023Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells derived from dental pulp that serves as an important model for investigating biological regeneration.... (Review)
Review
Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells derived from dental pulp that serves as an important model for investigating biological regeneration. DPSCs have a multipotent differentiation capacity and can promote different biological processes, including osteogenesis, odontogenesis, chondrogenesis, and angiogenesis. These biological processes are regulated by an extensive range of intra- and extra-cellular factors. Further, biomechanical cues, such as substrate stiffness, physical stress, and cell spreading, have been highlighted as particularly important modulators of DPSC function. This review sought to discuss various related signaling components involved in biomechanical cues and their respective roles in cellular and tissue responses in DPSCs, summarize current findings, and provide an outlook on the potential applications of biomechanics in regenerative medicine and tissue engineering.
Topics: Stem Cells; Dental Pulp; Cell Differentiation; Osteogenesis; Mesenchymal Stem Cells; Cells, Cultured; Cell Proliferation
PubMed: 37919075
DOI: 10.31083/j.fbl2810274 -
Anatomical Record (Hoboken, N.J. : 2007) Nov 2023Herein, we compared the developmental maturity of the cranium, limbs, and feeding apparatus in a perinatal common vampire bat relative to its mother. In addition, we...
Herein, we compared the developmental maturity of the cranium, limbs, and feeding apparatus in a perinatal common vampire bat relative to its mother. In addition, we introduce a method for combining two computed tomographic imaging techniques to three-dimensionally reconstruct endocasts in poorly ossified crania. The Desmodus specimens were scanned using microcomputed tomography (microCT) and diffusible iodine-based contrast-enhanced CT to image bone and soft tissues. Muscles of the jaw and limbs, and the endocranial cavity were segmented using imaging software. Endocranial volume (ECV) of the perinatal Desmodus is 74% of adult ECV. The facial skeletal is less developed (e.g., palatal length 60% of adult length), but volumes for alveolar crypts/sockets of permanent teeth are nearly identical. The forelimb skeleton is uniformly less ossified than the distal hind limb, with no secondary centers ossified and an entirely cartilaginous carpus. All epiphyseal growth zones are active in the brachium and antebrachium, with the distal radius exhibiting the greatest number of proliferating chondrocytes arranged in columns. The hind limb skeleton is precociously ossified from the knee distally. The musculature of the fore limb, temporalis, and masseter muscles appear weakly developed (6-11% of the adult volume). In contrast, the leg and foot musculature is better developed (23-25% of adult volume), possibly enhancing the newborn's capability to grip the mother's fur. Desmodus is born relatively large, and our results suggest they are born neurally and dentally precocious, with generally underdeveloped limbs, especially the fore limb.
Topics: Animals; Infant, Newborn; Humans; X-Ray Microtomography; Skull; Osteogenesis; Muscles; Lower Extremity
PubMed: 36806921
DOI: 10.1002/ar.25179 -
ELife Nov 2023The role of regulated cell death in organ development, particularly the impact of non-apoptotic cell death, remains largely uncharted. Ferroptosis, a non-apoptotic cell...
The role of regulated cell death in organ development, particularly the impact of non-apoptotic cell death, remains largely uncharted. Ferroptosis, a non-apoptotic cell death pathway known for its iron dependence and lethal lipid peroxidation, is currently being rigorously investigated for its pathological functions. The balance between ferroptotic stress (iron and iron-dependent lipid peroxidation) and ferroptosis supervising pathways (anti-lipid peroxidation systems) serves as the key mechanism regulating the activation of ferroptosis. Compared with other forms of regulated necrotic cell death, ferroptosis is critically related to the metabolism of lipid and iron which are also important in organ development. In our study, we examined the role of ferroptosis in organogenesis using an ex vivo tooth germ culture model, investigating the presence and impact of ferroptotic stress on tooth germ development. Our findings revealed that ferroptotic stress increased during tooth development, while the expression of glutathione peroxidase 4 (Gpx4), a crucial anti-lipid peroxidation enzyme, also escalated in dental epithelium/mesenchyme cells. The inhibition of ferroptosis was found to partially rescue erastin-impaired tooth morphogenesis. Our results suggest that while ferroptotic stress is present during tooth organogenesis, its effects are efficaciously controlled by the subsequent upregulation of Gpx4. Notably, an overabundance of ferroptotic stress, as induced by erastin, suppresses tooth morphogenesis.
Topics: Odontogenesis; Organogenesis; Ferroptosis; Lipid Peroxidation; Iron
PubMed: 37991825
DOI: 10.7554/eLife.88745 -
Hematology Reports Aug 2023Acute lymphocytic leukemia (ALL) is the most frequent form of all childhood leukemias, mostly affecting children between 2 and 4 years old. Oral symptoms, such as mouth... (Review)
Review
Acute lymphocytic leukemia (ALL) is the most frequent form of all childhood leukemias, mostly affecting children between 2 and 4 years old. Oral symptoms, such as mouth ulcers, mucositis, xerostomia, Herpes or Candidiasis, gingival enlargement and bleeding, petechiae, erythema, mucosal pallor and atrophic glossitis, are very common symptoms of ALL and can be early signs of the disease. Secondary and tertiary complications, a direct effect of chemo and radiotherapy, are associated with more severe bleeding, higher susceptibility to infections, ulcerations, inflammation of the mucous membranes, osteoradionecrosis, xerostomia, taste alterations, trismus, carious lesions and dental abnormalities. Immunotherapy, though less toxic, causes oral dysesthesia and pain. Overall, the effects in the oral cavity are transient but there are long-term consequences like caries, periodontal disease and tooth loss that impair endodontic and orthodontic treatments. Also, dental abnormalities resulting from disturbed odontogenesis are known to affect a child's quality of life. The medical dentist should identify these complications and perform appropriate oral care in tandem with other health professionals. Thus, poor oral hygiene can lead to systemic ALL complications. The aim of this review is to describe the oral complications in children with ALL who are undergoing chemo, radio or immunotherapy.
PubMed: 37754666
DOI: 10.3390/hematolrep15030051 -
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