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Colloids and Surfaces. B, Biointerfaces Sep 2023Exosomes are produced by all the cells and exist in all body fluids. They have been regarded as potentially promising to diagnostic biomarkers and therapeutic bioactive... (Review)
Review
Exosomes are produced by all the cells and exist in all body fluids. They have been regarded as potentially promising to diagnostic biomarkers and therapeutic bioactive mediators since they transport DNA, RNA and protein information from cell to cell. Herein, we summarized the recent research about exosomes from gingival crevicular fluid, saliva and serum used as diagnostic markers in periodontitis and dental caries. Moreover, we highlighted the mechanisms of exosomes in dental pulp regeneration and periodontal regeneration, as well as the technological innovation of exosome delivery methods in oral disease. In the end, this review discussed the advantages and future challenges of exosomes in real clinical applications.
Topics: Humans; Exosomes; Dental Caries; Dental Pulp; Regeneration; Biomarkers
PubMed: 37451223
DOI: 10.1016/j.colsurfb.2023.113429 -
Cureus Aug 2023Silver nanoparticles (AgNPs) have been effectively applicable in most regions because of their antimicrobial activity against various microorganisms. AgNPs can be... (Review)
Review
Silver nanoparticles (AgNPs) have been effectively applicable in most regions because of their antimicrobial activity against various microorganisms. AgNPs can be applied in disinfection and prophylaxis and to prevent diseases of the oral cavity. Because of developing interest in AgNPs, this article shows the application of AgNPs in various fields of dentistry such as nanocomposites, implant coatings, inhibiting the growth of bacteria, preventing dental caries, biofilm, infectious microbes, local anesthesia, microorganisms causing damage to the pulp, as well as deals with diseases such as oral malignancies due to their antitumor properties. AgNPs have a potential system with major features including antibacterial, anti-inflammatory, and anticancer action. They may also be used as a sustained drug delivery vehicle.
PubMed: 37750112
DOI: 10.7759/cureus.44090 -
BMC Oral Health Nov 2023N6-methyladenosine (mA) RNA modification regulators play an important role in many human diseases, and its abnormal expression can lead to the occurrence and development...
BACKGROUND
N6-methyladenosine (mA) RNA modification regulators play an important role in many human diseases, and its abnormal expression can lead to the occurrence and development of diseases. However, their significance in pulpitis remains largely unknown. Here, we sought to identify and validate the mA RNA regulatory network in pulpitis.
METHODS
Gene expression data for mA regulators in human pulpitis and normal pulp tissues from public GEO databases were analyzed. Bioinformatics analysis including Gene ontology (GO) functional, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed by R package, and Cytoscape software was used to study the role of mA miRNA-mRNA regulatory network in pulpitis. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression of key mA regulators in collected human pulpitis specimens.
RESULTS
Differential genes between pulpitis and normal groups were found from the GEO database, and further analysis found that there were significant differences in the mA modification-related genes ALKBH5, METTL14, METTL3, METTL16, RBM15B and YTHDF1. And their interaction relationships and hub genes were determined. The hub m6A regulator targets were enriched in immune cells differentiation, glutamatergic synapse, ephrin receptor binding and osteoclast differentiation in pulpitis. Validation by qRT-PCR showed that the expression of methylases METTL14 and METTL3 was decreased, thus these two genes may play a key role in pulpitis.
CONCLUSION
Our study identified and validated the mA RNA regulatory network in pulpitis. These findings will provide valuable resource to guide the mechanistic and therapeutic analysis of the role of key mA modulators in pulpitis.
Topics: Humans; Pulpitis; MicroRNAs; RNA, Messenger; Dental Pulp; Computational Biology; Methyltransferases
PubMed: 37978362
DOI: 10.1186/s12903-023-03578-8 -
Journal of Dental Research May 2024Endodontics is the dental specialty foremost concerned with diseases of the pulp and periradicular tissues. Clinicians often face patients with varying symptoms, must... (Review)
Review
Endodontics is the dental specialty foremost concerned with diseases of the pulp and periradicular tissues. Clinicians often face patients with varying symptoms, must critically assess radiographic images in 2 and 3 dimensions, derive complex diagnoses and decision making, and deliver sophisticated treatment. Paired with low intra- and interobserver agreement for radiographic interpretation and variations in treatment outcome resulting from nonstandardized clinical techniques, there exists an unmet need for support in the form of artificial intelligence (AI), providing automated biomedical image analysis, decision support, and assistance during treatment. In the past decade, there has been a steady increase in AI studies in endodontics but limited clinical application. This review focuses on critically assessing the recent advancements in endodontic AI research for clinical applications, including the detection and diagnosis of endodontic pathologies such as periapical lesions, fractures and resorptions, as well as clinical treatment outcome predictions. It discusses the benefits of AI-assisted diagnosis, treatment planning and execution, and future directions including augmented reality and robotics. It critically reviews the limitations and challenges imposed by the nature of endodontic data sets, AI transparency and generalization, and potential ethical dilemmas. In the near future, AI will significantly affect the everyday endodontic workflow, education, and continuous learning.
PubMed: 38822561
DOI: 10.1177/00220345241255593 -
International Endodontic Journal Aug 2023Biallelic loss-of-function FAM20A mutations cause amelogenesis imperfecta (AI) type IG, better known as enamel renal syndrome (ERS), characterized by severe enamel...
AIM
Biallelic loss-of-function FAM20A mutations cause amelogenesis imperfecta (AI) type IG, better known as enamel renal syndrome (ERS), characterized by severe enamel hypoplasia, delayed/failed tooth eruption, intrapulpal calcifications, gingival hyperplasia and nephrocalcinosis. FAM20A binds to FAM20C, the Golgi casein kinase (GCK) and potentiates its function to phosphorylate secreted proteins critical for biomineralization. While many FAM20A pathogenic mutations have been reported, the pathogeneses of orodental anomalies in ERS remain to be elucidated. This study aimed to identify disease-causing mutations for patients with ERS phenotypes and to discern the molecular mechanism underlying ERS intrapulpal calcifications.
METHODOLOGY
Phenotypic characterization and whole exome analyses were conducted for 8 families and 2 sporadic cases with hypoplastic AI. A minigene assay was performed to investigate the molecular consequences of a FAM20A splice-site variant. RNA sequencing followed by transcription profiling and gene ontology (GO) analyses were carried out for dental pulp tissues of ERS and the control.
RESULTS
Biallelic FAM20A mutations were demonstrated for each affected individual, including 7 novel pathogenic variants: c.590-5T>A, c.625T>A (p.Cys209Ser), c.771del (p.Gln258Argfs*28), c.832_835delinsTGTCCGACGGTGTCCGACGGTGTC CA (p.Val278Cysfs*29), c.1232G>A (p.Arg411Gln), c.1297A>G (p.Arg433Gly) and c.1351del (p.Gln451Serfs*4). The c.590-5T>A splice-site mutation caused Exon 3 skipping, which resulted in an in-frame deletion of a unique region of the FAM20A protein, p.(Asp197_Ile214delinsVal). Analyses of differentially expressed genes in ERS pulp tissues demonstrated that genes involved in biomineralization, particularly dentinogenesis, were significantly upregulated, such as DSPP, MMP9, MMP20 and WNT10A. Enrichment analyses indicated overrepresentation of gene sets associated with BMP and SMAD signalling pathways. In contrast, GO terms related to inflammation and axon development were underrepresented. Among BMP signalling genes, BMP agonists GDF7, GDF15, BMP3, BMP8A, BMP8B, BMP4 and BMP6 were upregulated, while BMP antagonists GREM1, BMPER and VWC2 showed decreased expression in ERS dental pulp tissues.
CONCLUSIONS
Upregulation of BMP signalling underlies intrapulpal calcifications in ERS. FAM20A plays an essential role in pulp tissue homeostasis and prevention of ectopic mineralization in soft tissues. This critical function probably depends upon MGP (matrix Gla protein), a potent mineralization inhibitor that must be properly phosphorylated by FAM20A-FAM20C kinase complex.
Topics: Humans; Nephrocalcinosis; Amelogenesis Imperfecta; Dental Pulp; Dental Enamel Proteins; Mutation; Calcinosis; Gene Expression Profiling; Carrier Proteins
PubMed: 37159186
DOI: 10.1111/iej.13928 -
Human Genomics Oct 2023Tooth agenesis is a common dental anomaly that can substantially affect both the ability to chew and the esthetic appearance of patients. This study aims to identify...
BACKGROUND
Tooth agenesis is a common dental anomaly that can substantially affect both the ability to chew and the esthetic appearance of patients. This study aims to identify possible genetic factors that underlie various forms of tooth agenesis and to investigate the possible molecular mechanisms through which human dental pulp stem cells may play a role in this condition.
RESULTS
Using whole-exome sequencing of a Han Chinese family with non-syndromic tooth agenesis, a rare mutation in FGFR1 (NM_001174063.2: c.103G > A, p.Gly35Arg) was identified as causative and confirmed by Sanger sequencing. Via GeneMatcher, another family with a known variant (NM_001174063.2: c.1859G > A, p.Arg620Gln) was identified and diagnosed with tooth agenesis and a rare genetic disorder with considerable intrafamilial variability. Fgfr1 is enriched in the ectoderm during early embryonic development of mice and showed sustained low expression during normal embryonic development of Xenopus laevis frogs. Functional studies of the highly conserved missense variant c.103G > A showed deleterious effects. FGFR1 (c.103G > A) was overexpressed compared to wildtype and promoted proliferation while inhibiting apoptosis in HEK293 and human dental pulp stem cells. Moreover, the c.103G > A variant was found to suppress the epithelial-mesenchymal transition. The variant could downregulate ID4 expression and deactivate the TGF-beta signaling pathway by promoting the expression of SMAD6 and SMAD7.
CONCLUSION
Our research broadens the mutation spectrum associated with tooth agenesis and enhances understanding of the underlying disease mechanisms of this condition.
Topics: Humans; HEK293 Cells; Anodontia; Mutation; Mutation, Missense; Receptor, Fibroblast Growth Factor, Type 1
PubMed: 37833774
DOI: 10.1186/s40246-023-00539-8 -
International Journal of Oral Science Dec 2023Elevated fibroblast growth factor 23 (FGF23) in X-linked hypophosphatemia (XLH) results in rickets and phosphate wasting, manifesting by severe bone and dental...
Elevated fibroblast growth factor 23 (FGF23) in X-linked hypophosphatemia (XLH) results in rickets and phosphate wasting, manifesting by severe bone and dental abnormalities. Burosumab, a FGF23-neutralizing antibody, an alternative to conventional treatment (phosphorus and active vitamin D analogs), showed significant improvement in the long bone phenotype. Here, we examined whether FGF23 antibody (FGF23-mAb) also improved the dentoalveolar features associated with XLH. Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg of FGF23-mAb for 2 months and compared to wild-type (WT) and vehicle (PBS) treated Hyp mice (n = 3-7 mice). Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice, the higher concentration resulting in a rescue similar to WT levels. FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones. Histology revealed improved mineralization of the dentoalveolar tissues, with a decreased amount of osteoid, predentin and cementoid. Better periodontal ligament attachment was also observed, evidenced by restoration of the acellular cementum. These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features. Taken together, our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment, heralding its benefit in clinics for dental abnormalities.
Topics: Humans; Male; Mice; Animals; Familial Hypophosphatemic Rickets; Fibroblast Growth Factor-23; Retrospective Studies; Fibroblast Growth Factors; Bone and Bones; Phosphates
PubMed: 38052774
DOI: 10.1038/s41368-023-00259-8 -
Scientific Reports Oct 2023Osteoimmune diseases, such as apical periodontitis, are prevalent, often painful, inflammatory conditions resulting in bone loss and reduced quality of life. There is...
Osteoimmune diseases, such as apical periodontitis, are prevalent, often painful, inflammatory conditions resulting in bone loss and reduced quality of life. There is growing evidence that the nociceptive fibers densely innervating affected tissues regulate disease progression; therefore, we hypothesized that nociceptors regulate the transcriptomic profile of the periapical osteolytic lesion in a mouse model of apical periodontitis. Male control and nociceptor-ablated mice underwent pulp exposures, and after 0, 7, or 14 days, total RNA from periapical tissues was submitted for sequencing and bioinformatic analysis. Pulp exposure triggers the differential expression of hundreds of genes over the course of infection. At 14 days post pulp exposure, 422 genes, including Tnf, Il1a, and Il1b, were differentially expressed between nociceptor-ablated and control mice with greater enrichment of biological processes related to inflammation in nociceptor-ablated mice. Nociceptor ablation regulates the transcriptomic profile of periapical lesions in a mouse model of apical periodontitis, shifting the gene expression profile to a greater enrichment of inflammatory genes, suggesting nociceptors play a role in the kinetics of the immune response. This newly uncovered neuro-immune axis and its mechanisms in apical periodontitis can be an important therapeutic target for the treatment of this prevalent disease.
Topics: Male; Mice; Animals; Transcriptome; Nociceptors; Quality of Life; Periapical Periodontitis; Periapical Tissue
PubMed: 37845223
DOI: 10.1038/s41598-023-44648-9 -
Journal of Bone and Mineral Research :... Aug 2023Chronic kidney disease (CKD) is characterized by kidney damage and loss of renal function. CKD mineral and bone disorder (CKD-MBD) describes the dysregulation of mineral...
Chronic kidney disease (CKD) is characterized by kidney damage and loss of renal function. CKD mineral and bone disorder (CKD-MBD) describes the dysregulation of mineral homeostasis, including hyperphosphatemia and elevated parathyroid hormone (PTH) secretion, skeletal abnormalities, and vascular calcification. CKD-MBD impacts the oral cavity, with effects including salivary gland dysfunction, enamel hypoplasia and damage, increased dentin formation, decreased pulp volume, pulp calcifications, and altered jaw bones, contributing to clinical manifestations of periodontal disease and tooth loss. Underlying mechanisms are not fully understood, and CKD mouse models commonly require invasive procedures with high rates of infection and mortality. We aimed to characterize the dentoalveolar effects of an adenine diet (AD)-induced CKD (AD-CKD) mouse model. Eight-week-old C57BL/6J mice were provided either a normal phosphorus diet control (CTR) or adenine and high-phosphorus diet CKD to induce kidney failure. Mice were euthanized at 15 weeks old, and mandibles were collected for micro-computed tomography and histology. CKD mice exhibited kidney failure, hyperphosphatemia, and hyperparathyroidism in association with porous cortical bone in femurs. CKD mice showed a 30% decrease in molar enamel volume compared to CTR mice. Enamel wear was associated with reduced ductal components, ectopic calcifications, and altered osteopontin (OPN) deposition in submandibular salivary glands of CKD mice. Molar cusps in CKD mice were flattened, exposing dentin. Molar dentin/cementum volume increased 7% in CKD mice and pulp volume decreased. Histology revealed excessive reactionary dentin and altered pulp-dentin extracellular matrix proteins, including increased OPN. Mandibular bone volume fraction decreased 12% and bone mineral density decreased 9% in CKD versus CTR mice. Alveolar bone in CKD mice exhibited increased tissue-nonspecific alkaline phosphatase localization, OPN deposition, and greater osteoclast numbers. AD-CKD recapitulated key aspects reported in CKD patients and revealed new insights into CKD-associated oral defects. This model has potential for studying mechanisms of dentoalveolar defects or therapeutic interventions. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Mice; Animals; Chronic Kidney Disease-Mineral and Bone Disorder; Adenine; X-Ray Microtomography; Hyperphosphatemia; Mice, Inbred C57BL; Renal Insufficiency, Chronic; Phosphorus
PubMed: 37191192
DOI: 10.1002/jbmr.4829 -
Zhonghua Kou Qiang Yi Xue Za Zhi =... Sep 2023The health of dental tissue is an important guarantee to obtain good orthodontic effect, and also the basis to achieve beauty, stability and function after orthodontic...
The health of dental tissue is an important guarantee to obtain good orthodontic effect, and also the basis to achieve beauty, stability and function after orthodontic treatment. The classification of dental diseases is complex and diverse, which has different effects on orthodontic treatment. It is necessary to make clear diagnosis before orthodontic treatment, and take preventive and therapeutic measures according to the etiology and clinical symptoms, so as to achieve the goal of health treatment. Orthodontic treatment might cause a variety of changes in the teeth and pulp tissue. Such changes have certain rules and are complex and variable. Orthodontist should master relevant knowledge to minimize the side effects of orthodontic treatment.
PubMed: 37659845
DOI: 10.3760/cma.j.cn112144-20230430-00176