Interplay of epigenetics and epistasis drives oral submucous fibrosis

Persistent injury to oral mucosa due to habitual quid chewing, resulting in the upregulation of inflammatory cytokines and consequential myofibroblastic persistence, emphasizes the role of epigenetic aberration in the pathogenesis of oral submucous fibrosis (OSF). However, there is a dearth of research on the role epistasis plays in the pathophysiology of OSF. Among the important epistatic interactions in the pathophysiology of OSF are those between Phosphatase and Tensin Homologue (PTEN) and Insulin-Like Growth Factor 1, Transforming Growth Factor-β (TGF-β), Cyclooxygenases, and lipoxygenases (LOX). Additionally, PTEN and Nuclear Factor Kappa B (NF-κB) have an epistatic relationship that is particularly mediated by the p65 subunit of NF-κB. Given the importance of epigenetic modification in the pathogenesis of OSF, the potential use of DNA methyltransferase and Histone deacetylase inhibitors as a therapeutic option holds promise. Another in vivo epigenetic therapeutic option for treating OSF is using stimulatory microRNAs against antifibrotic genes and inhibitory microRNAs against profibrotic genes. This review aims to connect numerous epigenetic and epistatic components to the mechanism of OSF. A better understanding of the disease process may provide OSF management with newer therapeutic options

The Cleft Palate And Lip: Embryology, Genetics, Environmental Influences, And Approaches To Surgical Repair

The cleft palate and lip is one of the most common birth defects that may or may not be syndromic. Clefting may manifest unilaterally or bilaterally with varying degrees of severity. In embryo, the upper and lower jaws were formed from the first brachial arches that descend from both sides and fuse. Many genetic loci and cell-signaling pathways have been identified with the fusion event, in which polar neural crest cells undergo the epithelial-to-mesenchymal transition. Genetic mutations, environmental teratogens, and nutrition have been associated with the cleft palate and lip. The extracellular matrix has been extensively studied to understand cell-cell communication and is crucial in tissue engineering. The gold standard today for palatal reconstruction remains to be an autogenous graft from the anterior iliac crest. Autogenous bone grafts have many disadvantages such as donor site morbidity. New approaches in tissue engineering involving stems cells, growth factors, and biomaterial scaffolding have been identified to avoid autogenous bone grafts. Mesenchymal cells may be harvested from dental tissue and adipocytes. Three-dimensional printing and computer-aided design are becoming widely used in oral surgery. More research are underway to overcome the challenges in soft tissue reconstruction of the soft palate

Clinical Perspectives of Non-Coding RNA in Oral Inflammatory Diseases and Neuropathic Pain: A Narrative Review

Non-coding RNAs (ncRNAs) represent a research hotspot by playing a key role in epigenetic and transcriptional regulation of diverse biological functions and due to their involvement in different diseases, including oral inflammatory diseases. Based on ncRNAs’ suitability for salivary biomarkers and their involvement in neuropathic pain and tissue regeneration signaling pathways, the present narrative review aims to highlight the potential clinical applications of ncRNAs in oral inflammatory diseases, with an emphasis on salivary diagnostics, regenerative dentistry, and precision medicine for neuropathic orofacial pain

Zinc Signaling in Physiology and Pathogenesis

The essential trace element zinc plays indispensable roles in multiple cellular processes. It regulates a great number of protein functions, including transcription factors, enzymes, adapters, and growth factors as a structural and/or catalytic factor. Recent studies have highlighted another function of zinc as an intra- and intercellular signaling mediator, which became recognized as the “zinc signal”. Indeed, zinc regulates cellular signaling pathways, which enable conversion of extracellular stimuli to intracellular signals, and controls various intracellular and extracellular events, and thus zinc mediates communication between cells. The zinc signal is essential for physiology, and its dysregulation causes a variety of diseases, such as diabetes, cancer, osteoarthritis, dermatitis, and dementia. This Special Issue focuses on crucial roles of zinc signaling in biological processes in molecular and physiological basis, addressing the future directions and questions underlying this unique phenomenon. Because there is growing interest and attention in physiopathological contribution of zinc signal, we believe this Special Issue will provide very timely information on it and thus should appeal to a wide range of readers

DPSCs regulate epithelial-T cell interactions in oral submucous fibrosis

Abstract Background Oral submucous fibrosis (OSF) is a precancerous lesion characterized by fibrous tissue deposition, the incidence of which correlates positively with the frequency of betel nut chewing. Prolonged betel nut chewing can damage the integrity of the oral mucosal epithelium, leading to chronic inflammation and local immunological derangement. However, currently, the underlying cellular events driving fibrogenesis and dysfunction are incompletely understood, such that OSF has few treatment options with limited therapeutic effectiveness. Dental pulp stem cells (DPSCs) have been recognized for their anti-inflammatory and anti-fibrosis capabilities, making them promising candidates to treat a range of immune, inflammatory, and fibrotic diseases. However, the application of DPSCs in OSF is inconclusive. Therefore, this study aimed to explore the pathogenic mechanism of OSF and, based on this, to explore new treatment options. Methods A human cell atlas of oral mucosal tissues was compiled using single-cell RNA sequencing to delve into the underlying mechanisms. Epithelial cells were reclustered to observe the heterogeneity of OSF epithelial cells and their communication with immune cells. The results were validated in vitro, in clinicopathological sections, and in animal models. In vivo, the therapeutic effect and mechanism of DPSCs were characterized by histological staining, immunohistochemical staining, scanning electron microscopy, and atomic force microscopy. Results A unique epithelial cell population, Epi1.2, with proinflammatory and profibrotic functions, was predominantly found in OSF. Epi1.2 cells also induced the fibrotic process in fibroblasts by interacting with T cells through receptor-ligand crosstalk between macrophage migration inhibitory factor (MIF)-CD74 and C-X-C motif chemokine receptor 4 (CXCR4). Furthermore, we developed OSF animal models and simulated the clinical local injection process in the rat buccal mucosa using DPSCs to assess their therapeutic impact and mechanism. In the OSF rat model, DPSCs demonstrated superior therapeutic effects compared with the positive control (glucocorticoids), including reducing collagen deposition and promoting blood vessel regeneration. DPSCs mediated immune homeostasis primarily by regulating the numbers of KRT19 + MIF + epithelial cells and via epithelial-stromal crosstalk. Conclusions Given the current ambiguity surrounding the cause of OSF and the limited treatment options available, our study reveals that epithelial cells and their crosstalk with T cells play an important role in the mechanism of OSF and suggests the therapeutic promise of DPSCs

Additional file 1 of DPSCs regulate epithelial-T cell interactions in oral submucous fibrosis

Supplementary Material