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ELife Jan 2023The interplay among different cells in a tissue is essential for maintaining homeostasis. Although disease states have been traditionally attributed to individual cell...
The interplay among different cells in a tissue is essential for maintaining homeostasis. Although disease states have been traditionally attributed to individual cell types, increasing evidence and new therapeutic options have demonstrated the primary role of multicellular functions to understand health and disease, opening new avenues to understand pathogenesis and develop new treatment strategies. We recently described the cellular composition and dynamics of the human oral mucosa; however, the spatial arrangement of cells is needed to better understand a morphologically complex tissue. Here, we link single-cell RNA sequencing, spatial transcriptomics, and high-resolution multiplex fluorescence hybridisation to characterise human oral mucosa in health and oral chronic inflammatory disease. We deconvolved expression for resolution enhancement of spatial transcriptomic data and defined highly specialised epithelial and stromal compartments describing location-specific immune programs. Furthermore, we spatially mapped a rare pathogenic fibroblast population localised in a highly immunogenic region, responsible for lymphocyte recruitment through and and with a possible role in pathological angiogenesis through . Collectively, our study provides a comprehensive reference for the study of oral chronic disease pathogenesis.
Topics: Humans; Chemokine CXCL10; Fibroblasts; Gene Expression Profiling; Lymphocytes; Transcriptome; Interleukin-8
PubMed: 36648332
DOI: 10.7554/eLife.81525 -
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 -
PeerJ 2023Cusp patterning on living and extinct primate molar teeth plays a crucial role in species diagnoses, phylogenetic inference, and the reconstruction of the evolutionary... (Review)
Review
Cusp patterning on living and extinct primate molar teeth plays a crucial role in species diagnoses, phylogenetic inference, and the reconstruction of the evolutionary history of the primate clade. These studies rely on a system of nomenclature that can accurately identify and distinguish between the various structures of the crown surface. However, studies at the enamel-dentine junction (EDJ) of some primate taxa have demonstrated a greater degree of cusp variation and expression at the crown surface than current systems of nomenclature allow. In this study, we review the current nomenclature and its applicability across all the major primate clades based on investigations of mandibular crown morphology at the enamel-dentine junction revealed through microtomography. From these observations, we reveal numerous new patterns of lower molar accessory cusp expression in primates. We highlight numerous discrepancies between the expected patterns of variation inferred from the current academic literature, and the new patterns of expected variation seen in this study. Based on the current issues associated with the crown nomenclature, and an incomplete understanding of the precise developmental processes associated with each individual crown feature, we introduce these structures within a conservative, non-homologous naming scheme that focuses on simple location-based categorisations. Until there is a better insight into the developmental and phylogenetic origin of these crown features, these categorisations are the most practical way of addressing these structures. Until then, we also suggest the cautious use of accessory cusps for studies of taxonomy and phylogeny.
Topics: Animals; Phylogeny; Tooth Crown; Primates; Tooth; Molar
PubMed: 36650833
DOI: 10.7717/peerj.14523 -
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 -
Organogenesis Dec 2022The development and repair of dentin are strictly regulated by hundreds of genes. Abnormal dentin development is directly caused by gene mutations and dysregulation....
The development and repair of dentin are strictly regulated by hundreds of genes. Abnormal dentin development is directly caused by gene mutations and dysregulation. Understanding and mastering this signal network is of great significance to the study of tooth development, tissue regeneration, aging, and repair and the treatment of dental diseases. It is necessary to understand the formation and repair mechanism of dentin in order to better treat the dentin lesions caused by various abnormal properties, whether it is to explore the reasons for the formation of dentin defects or to develop clinical drugs to strengthen the method of repairing dentin. Molecular biology of genes related to dentin development and repair are the most important basis for future research.
Topics: Dentin; Dentinogenesis; Odontoblasts; Odontogenesis
PubMed: 35023442
DOI: 10.1080/15476278.2021.2022373 -
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 -
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 -
Journal of Dental Research Aug 2023Tooth enamel is generated by ameloblasts. Any failure in amelogenesis results in defects in the enamel, a condition known as amelogenesis imperfecta. Here, we report...
Tooth enamel is generated by ameloblasts. Any failure in amelogenesis results in defects in the enamel, a condition known as amelogenesis imperfecta. Here, we report that mice with deficient autophagy in epithelial-derived tissues ( and conditional knockout mice) exhibit amelogenesis imperfecta. Micro-computed tomography imaging confirmed that enamel density and thickness were significantly reduced in the teeth of these mice. At the molecular level, ameloblast differentiation was compromised through ectopic accumulation and activation of NRF2, a specific substrate of autophagy. Through bioinformatic analyses, we identified , , , , , and as candidate genes related to amelogenesis imperfecta and the NRF2-mediated pathway. To investigate the effects of the ectopic NRF2 pathway activation caused by the autophagy deficiency, we analyzed target gene expression and NRF2 binding to the promoter region of candidate target genes and found suppressed gene expression of , , , and but not of and . Taken together, our findings indicate that autophagy plays a crucial role in ameloblast differentiation and that its failure results in amelogenesis imperfecta through ectopic NRF2 activation.
Topics: Mice; Animals; Ameloblasts; Amelogenesis Imperfecta; X-Ray Microtomography; NF-E2-Related Factor 2; Amelogenesis; Mice, Knockout; Tumor Suppressor Proteins; Repressor Proteins
PubMed: 37249312
DOI: 10.1177/00220345231169220 -
International Journal of Oral Science Feb 2024Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious... (Review)
Review
Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multi-disciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.
Topics: Humans; Maxillary Sinusitis; Consensus; Maxillary Sinus; Odontogenesis; Rhinosinusitis
PubMed: 38302479
DOI: 10.1038/s41368-024-00278-z -
Journal of Dental Research Jul 2022Tooth agenesis is a common structural birth defect in humans that results from failure of morphogenesis during early tooth development. The homeobox transcription factor...
Tooth agenesis is a common structural birth defect in humans that results from failure of morphogenesis during early tooth development. The homeobox transcription factor Msx1 and the canonical Wnt signaling pathway are essential for "bud to cap" morphogenesis and are causal factors for tooth agenesis. Our recent study suggested that Msx1 regulates Wnt signaling during early tooth development by suppressing the expression of and in the tooth bud mesenchyme, and it demonstrated partial rescue of -deficient molar teeth by a combination of DKK inhibition and genetic inactivation of SFRPs. In this study, we found that Sostdc1/Wise, another secreted Wnt antagonist, is involved in regulating the odontogenic pathway downstream of Msx1. Whereas expression in the developing tooth germ was not increased in embryos, genetic inactivation of rescued maxillary molar, but not mandibular molar, morphogenesis in mice with full penetrance. Since the ; embryos exhibited ectopic expression in the developing dental mesenchyme, similar to embryos, we generated and analyzed tooth development in ; double and ;; triple mutant mice. The ; double mutants showed rescued maxillary molar morphogenesis at high penetrance, with a small percentage also exhibiting mandibular molars that transitioned to the cap stage. Furthermore, tooth development was rescued in the maxillary and mandibular molars, with full penetrance, in the ;; mice. Together, these data reveal 1) that a key role of Msx1 in driving tooth development through the bud-to-cap transition is to control the expression of and 2) that modulation of Wnt signaling activity by Dkk2 and Sostdc1 plays a crucial role in the Msx1-dependent odontogenic pathway during early tooth morphogenesis.
Topics: Animals; Bone Morphogenetic Protein 4; Gene Expression Regulation, Developmental; MSX1 Transcription Factor; Mesoderm; Mice; Morphogenesis; Odontogenesis; Tooth; Tooth Germ; Wnt Signaling Pathway
PubMed: 35114852
DOI: 10.1177/00220345211070583