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Aging Cell Mar 2024Once tooth development is complete, odontoblasts and their progenitor cells in the dental pulp play a major role in protecting tooth vitality from external stresses....
Once tooth development is complete, odontoblasts and their progenitor cells in the dental pulp play a major role in protecting tooth vitality from external stresses. Hence, understanding the homeostasis of the mature pulp populations is just as crucial as understanding that of the young, developing ones for managing age-related dentinal damage. Here, it is shown that loss of Cpne7 accelerates cellular senescence in odontoblasts due to oxidative stress and DNA damage accumulation. Thus, in Cpne7-null dental pulp, odontoblast survival is impaired, and aberrant dentin is extensively formed. Intraperitoneal or topical application of CPNE7-derived functional peptide, however, alleviates the DNA damage accumulation and rescues the pathologic dentin phenotype. Notably, a healthy dentin-pulp complex lined with metabolically active odontoblasts is observed in 23-month-old Cpne7-overexpressing transgenic mice. Furthermore, physiologic dentin was regenerated in artificial dentinal defects of Cpne7-overexpressing transgenic mice. Taken together, Cpne7 is indispensable for the maintenance and homeostasis of odontoblasts, while promoting odontoblastic differentiation of the progenitor cells. This research thereby introduces its potential in oral disease-targeted applications, especially age-related dental diseases involving dentinal loss.
Topics: Mice; Animals; Aging, Premature; Dental Pulp; Cellular Senescence; Odontoblasts; Cell Differentiation; Mice, Transgenic
PubMed: 38105557
DOI: 10.1111/acel.14061 -
Journal of Conservative Dentistry and... 2023Artificial intelligence (AI) technology has mostly been used by dental practitioners to diagnose problems, plan treatments, make clinical judgments, and predict... (Review)
Review
Artificial intelligence (AI) technology has mostly been used by dental practitioners to diagnose problems, plan treatments, make clinical judgments, and predict outcomes. In endodontics, convolutional neural networks and artificial neural networks, two types of (AI) models, have been used to study the anatomy of the root canal system, measure the length of root canal, identify periapical pathology and root fractures, prediction of success of retreatment procedures, and dental pulp stem cells viability. The goal of this review is to assess AI's role in conservative dentistry and endodontics.
PubMed: 38292353
DOI: 10.4103/JCDE.JCDE_7_23 -
Stem Cell Reviews and Reports Nov 2023The potential therapeutic role of the Dental Pulp Stem Cells Secretome (SECR) in a rat model of experimentally induced Temporomandibular Joint (TMJ) Osteoarthritis (OA)...
The potential therapeutic role of the Dental Pulp Stem Cells Secretome (SECR) in a rat model of experimentally induced Temporomandibular Joint (TMJ) Osteoarthritis (OA) was evaluated. Proteomic profiling of the human SECR under specific oxygen tension (5% O2) and stimulation with Tumor Necrosis Factor-alpha (TNF-α) was performed. SECR and respective cell lysates (CL) samples were collected and subjected to SDS-PAGE, followed by LC-MS/MS analysis. The identified proteins were analyzed with Bioinformatic tools. The anti-inflammatory properties of SECR were assessed via an in vitro murine macrophages model, and were further validated in vivo, in a rat model of chemically-induced TMJ-OA by weekly recording of the head withdrawal threshold, the food intake, and the weight change, and radiographically and histologically at 4- and 8-weeks post-treatment. SECR analysis revealed the presence of 50 proteins that were enriched and/or statistically significantly upregulated compared to CL, while many of those proteins were involved in pathways related to "extracellular matrix organization" and "immune system". SECR application in vitro led to a significant downregulation on the expression of pro-inflammatory genes (MMP-13, MMP-9, MMP-3 and MCP-1), while maintaining an increased expression of IL-10 and IL-6. SECR application in vivo had a significant positive effect on all the clinical parameters, resulting in improved food intake, weight, and pain suppression. Radiographically, SECR application had a significant positive effect on trabecular bone thickness and bone density compared to the saline-treated group. Histological analysis indicated that SECR administration reduced inflammation, enhanced ECM and subchondral bone repair and regeneration, thus alleviating TMJ degeneration.
Topics: Rats; Humans; Mice; Animals; Chromatography, Liquid; Proteomics; Secretome; Tandem Mass Spectrometry; Temporomandibular Joint; Osteoarthritis; Stem Cells
PubMed: 37751010
DOI: 10.1007/s12015-023-10628-9 -
Bioactive Materials Aug 2024Microorganisms, physical factors such as temperature or mechanical injury, and chemical factors such as free monomers from composite resin are the main causes of dental... (Review)
Review
Microorganisms, physical factors such as temperature or mechanical injury, and chemical factors such as free monomers from composite resin are the main causes of dental pulp diseases. Current clinical treatment methods for pulp diseases include the root canal therapy, vital pulp therapy and regenerative endodontic therapy. Regenerative endodontic therapy serves the purpose of inducing the regeneration of new functional pulp tissues through autologous revascularization or pulp tissue engineering. This article first discusses the current clinical methods and reviews strategies as well as the research outcomes regarding the pulp regeneration. Then the in vivo models, the prospects and challenges for regenerative endodontic therapy were further discussed.
PubMed: 38745589
DOI: 10.1016/j.bioactmat.2024.04.031 -
Dental Materials : Official Publication... Apr 2024Although the introduction of self-adhesive composites in restorative dentistry is very promising, the innovation of new materials also presents challenges and unknowns....
OBJECTIVES
Although the introduction of self-adhesive composites in restorative dentistry is very promising, the innovation of new materials also presents challenges and unknowns. Therefore, the aim of this study was to investigate the cytotoxicity of four different self-adhesive composites (SAC) in vitro and to compare them with resin-modified glass ionomer cements (RM-GIC), a more established group of materials.
METHODS
Samples of the following materials were prepared according to ISO 7405/10993-12 and eluted in cell culture medium for 24 h at 37 °C: Vertise Flow, Fusio Liquid Dentin, Constic, Surefil One, Photac Fil and Fuji II LC. Primary human pulp cells were obtained from extracted wisdom teeth and cultured for 24 h with the extracts in serial dilutions. Cell viability was evaluated by MTT assay, membrane disruption was quantified by LDH assay and apoptosis was assessed by flow cytometry after annexin/PI staining.
RESULTS
Two SAC (Constic and Vertise Flow) and one RM-GIC (Photac Fil) significantly reduced cell viability by more than 30% compared to the untreated control (p < 0.001). Disruptive cell morphological changes were observed and the cells showed signs of late apoptosis and necrosis in flow cytometry. Membrane disruption was not observed with any of the investigated materials.
CONCLUSION
Toxic effects occurred independently of the substance group and need to be considered in the development of materials with regard to clinical implications.
CLINICAL SIGNIFICANCE
SAC have many beneficial qualities, however, the cytotoxic effects of certain products should be considered when applied in close proximity to the dental pulp, as is often required.
Topics: Humans; Resin Cements; Dental Cements; Composite Resins; Glass Ionomer Cements; Materials Testing; Dental Materials
PubMed: 38403539
DOI: 10.1016/j.dental.2024.02.015 -
Frontiers in Immunology 2023Pain within the trigeminal system, particularly dental pain, is poorly understood. This study aimed to determine whether single or multiple dental pulp injuries induce...
Electroacupuncture exerts prolonged analgesic and neuroprotective effects in a persistent dental pain model induced by multiple dental pulp injuries: GABAergic interneurons-astrocytes interaction.
Pain within the trigeminal system, particularly dental pain, is poorly understood. This study aimed to determine whether single or multiple dental pulp injuries induce persistent pain, its association with trigeminal central nociceptive pathways and whether electroacupuncture (EA) provides prolonged analgesic and neuroprotective effects in a persistent dental pain model. Models of single dental pulp injury (SDPI) and multiple dental pulp injuries (MDPI) were used to induce trigeminal neuropathic pain. The signs of dental pain-related behavior were assessed using the mechanical head withdrawal threshold (HWT). Immunofluorescence and western blot protocols were used to monitor astrocyte activation, changes in apoptosis-related proteins, and GABAergic interneuron plasticity. SDPI mice exhibited an initial marked decrease in HWT from days one to 14, followed by progressive recovery from days 21 to 42. From days 49 to 70, the HWT increased and returned to the control values. In contrast, MDPI mice showed a persistent decrease in HWT from days one to 70. MDPI increased glial fibrillary acidic protein (GFAP) and decreased glutamine synthetase (GS) and glutamate transporter-1 (GLT1) expression in the Vi/Vc transition zone of the brainstem on day 70, whereas no changes in astrocytic markers were observed on day 70 after SDPI. Increased expression of cleaved cysteine-aspartic protease-3 (cleaved caspase-3) and Bcl-2-associated X protein (Bax), along with decreased B-cell lymphoma/leukemia 2 (Bcl-2), were observed at day 70 after MDPI but not after SDPI. The downregulation of glutamic acid decarboxylase (GAD65) expression was observed on day 70 only after MDPI. The effects of MDPI-induced lower HWT from days one to 70 were attenuated by 12 sessions of EA treatment (days one to 21 after MDPI). Changes in astrocytic GFAP, GS, and GLT-1, along with cleaved caspase-3, Bax, Bcl-2, and GAD65 expression observed 70 days after MDPI, were reversed by EA treatment. The results suggest that persistent dental pain in mice was induced by MDPI but not by SDPI. This effect was associated with trigeminal GABAergic interneuron plasticity along with morphological and functional changes in astrocytes. EA exerts prolonged analgesic and neuroprotective effects that might be associated with the modulation of neuron-glia crosstalk mechanisms.
Topics: Mice; Animals; Astrocytes; Neuroprotective Agents; Caspase 3; bcl-2-Associated X Protein; Electroacupuncture; Dental Pulp; Neuralgia; Analgesics; Interneurons
PubMed: 37954604
DOI: 10.3389/fimmu.2023.1213710 -
Stem Cell Research & Therapy Aug 2023Redox signaling and energy metabolism are known to be involved in controlling the balance between self-renewal and proliferation/differentiation of stem cells. In this...
BACKGROUND
Redox signaling and energy metabolism are known to be involved in controlling the balance between self-renewal and proliferation/differentiation of stem cells. In this study we investigated metabolic and redox changes occurring during in vitro human dental pulp stem cells (hDPSCs) osteoblastic (OB) differentiation and tested on them the impact of the reactive oxygen species (ROS) signaling.
METHODS
hDPSCs were isolated from dental pulp and subjected to alkaline phosphatase and alizarin red staining, q-RT-PCR, and western blotting analysis of differentiation markers to assess achievement of osteogenic/odontogenic differentiation. Moreover, a combination of metabolic flux analysis and confocal cyto-imaging was used to profile the metabolic phenotype and to evaluate the redox tone of hDPSCs.
RESULTS
In differentiating hDPSCs we observed the down-regulation of the mitochondrial respiratory chain complexes expression since the early phase of the process, confirmed by metabolic flux analysis, and a reduction of the basal intracellular peroxide level in its later phase. In addition, dampened glycolysis was observed, thereby indicating a lower energy-generating phenotype in differentiating hDPSCs. Treatment with the ROS scavenger Trolox, applied in the early-middle phases of the process, markedly delayed OB differentiation of hDPSCs assessed as ALP activity, Runx2 expression, mineralization capacity, expression of stemness and osteoblast marker genes (Nanog, Lin28, Dspp, Ocn) and activation of ERK1/2. In addition, the antioxidant partly prevented the inhibitory effect on cell metabolism observed following osteogenic induction.
CONCLUSIONS
Altogether these results provided evidence that redox signaling, likely mediated by peroxide species, influenced the stepwise osteogenic expansion/differentiation of hDPSCs and contributed to shape its accompanying metabolic phenotype changes thus improving their efficiency in bone regeneration and repair.
Topics: Humans; Osteogenesis; Dental Pulp; Reactive Oxygen Species; Bone Regeneration; Energy Metabolism; Oxidation-Reduction; Niacinamide; Alkaline Phosphatase
PubMed: 37608350
DOI: 10.1186/s13287-023-03447-9 -
International Journal of Biological... Mar 2024In the last ten years, remarkable characteristics and a variety of functionalities have been created in biopolymeric materials for clinical dental applications. This... (Review)
Review
In the last ten years, remarkable characteristics and a variety of functionalities have been created in biopolymeric materials for clinical dental applications. This review gives an overview of current knowledge of natural biopolymers (biological macromolecules) in terms of structural, functional, and property interactions. Natural biopolymers such as polysaccharides (chitosan, bacterial cellulose, hyaluronic acid, and alginate) and polypeptides (collagen and silk fibroin) have been discussed for dental uses. These biopolymers exhibit excellent properties alone and when employed with other composite molecules making them ideal for treatment of periodontitis, endodontics, dental pulp regeneration and oral wound healing. These biopolymers together with the composite materials exhibit better biocompatibility, inertness, elasticity and flexibility which makes them a leading candidate to be used for other dental applications like caries management, oral appliances, dentures, dental implants and oral surgeries.
Topics: Dental Pulp; Regeneration; Polysaccharides; Biopolymers; Collagen; Dentistry; Biocompatible Materials
PubMed: 38185301
DOI: 10.1016/j.ijbiomac.2024.129215 -
Journal of Endodontics Jan 2024This study aimed to assess pulp survival in a randomized trial on pulp lavage in adult nonpainful posterior teeth with carious pulp exposure. The treatment included... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
This study aimed to assess pulp survival in a randomized trial on pulp lavage in adult nonpainful posterior teeth with carious pulp exposure. The treatment included complete caries excavation, direct pulp capping with mineral trioxide aggregate, and immediate restoration with composite resin.
METHODS
Fluid was collected from the pulp wound to assess matrix metalloproteinase-9 (MMP-9) and total protein values. Before pulp capping, cavities were randomly (block randomization, n = 48) washed with a physiological saline or a sodium hypochlorite solution (2.5% NaOCl). Treatment outcome was assessed clinically (cold test) and radiographically after at least 1 year and again after at least 3 years. Painful failures were differentiated from nonpainful failures. Pulp survival was estimated using the Kaplan-Meier method including 95% confidence intervals (CIs) up to 1500 days.
RESULTS
From the 96 patients originally enrolled, 73 individuals could be followed continuously. The clinical observations indicated a beneficial and sustained effect of pulp lavage with 2.5% NaOCl over a control treatment with physiological saline solution on estimated pulp survival 1500 days postintervention, with 7% (95% CI, 1%-40%) in the saline group versus 55% (95% CI, 30%-100%) in the NaOCl group. High MMP-9/total protein values in pulpal fluid collected from the exposed site indicated early and painful treatment failures yet were not associated with failures that occurred more than 250 days after intervention.
CONCLUSIONS
The low 4-year success rates reported here challenge the concept of direct pulp capping in the cases that were included. NaOCl lavage did not only increase the survival of affected pulps substantially but also particularly diminished painful failures (33% in the NaOCl group vs 62% in the saline group). The lack of the predictive value of MMP-9 assessments beyond early treatment failures points to inflammatory states of the pulp tissue under deep caries, which are not related to neutrophil infiltration.
Topics: Adult; Humans; Dental Pulp Capping; Matrix Metalloproteinase 9; Calcium Compounds; Silicates; Dental Pulp; Root Canal Therapy; Treatment Outcome; Dental Caries; Oxides; Drug Combinations; Pulp Capping and Pulpectomy Agents
PubMed: 37890614
DOI: 10.1016/j.joen.2023.10.008 -
Frontiers in Medicine 2024Bone defects resulting from severe trauma, tumors, inflammation, and other factors are increasingly prevalent. Stem cell-based therapies have emerged as a promising... (Review)
Review
Bone defects resulting from severe trauma, tumors, inflammation, and other factors are increasingly prevalent. Stem cell-based therapies have emerged as a promising alternative. Dental pulp stem cells (DPSCs), sourced from dental pulp, have garnered significant attention owing to their ready accessibility and minimal collection-associated risks. Ongoing investigations into DPSCs have revealed their potential to undergo osteogenic differentiation and their capacity to secrete a diverse array of ontogenetic components, such as extracellular vesicles and cell lysates. This comprehensive review article aims to provide an in-depth analysis of DPSCs and their secretory components, emphasizing extraction techniques and utilization while elucidating the intricate mechanisms governing bone regeneration. Furthermore, we explore the merits and demerits of cell and cell-free therapeutic modalities, as well as discuss the potential prospects, opportunities, and inherent challenges associated with DPSC therapy and cell-free therapies in the context of bone regeneration.
PubMed: 38487022
DOI: 10.3389/fmed.2024.1339573