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International Journal of Molecular... Jun 2024Epigenetic modulation, including histone modification, alters gene expression and controls cell fate. Histone deacetylases (HDACs) are identified as important regulators...
Epigenetic modulation, including histone modification, alters gene expression and controls cell fate. Histone deacetylases (HDACs) are identified as important regulators of dental pulp cell (DPC) mineralisation processes. Currently, there is a paucity of information regarding the nature of histone modification and HDAC expression in the dentine-pulp complex during dentinogenesis. The aim of this study was to investigate post-translational histone modulation and HDAC expression during DPC mineralisation and the expression of Class I/II HDACs during tooth development and in adult teeth. HDAC expression (isoforms -1 to -6) was analysed in mineralising primary rat DPCs using qRT-PCR and Western blot with mass spectrometry being used to analyse post-translational histone modifications. Maxillary molar teeth from postnatal and adult rats were analysed using immunohistochemical (IHC) staining for HDACs (1-6). HDAC-1, -2, and -4 protein expression increased until days 7 and 11, but decreased at days 14 and 21, while other HDAC expression increased continuously for 21 days. The Class II mineralisation-associated HDAC-4 was strongly expressed in postnatal sample odontoblasts and DPCs, but weakly in adult teeth, while other Class II HDACs (-5, -6) were relatively strongly expressed in postnatal DPCs and adult odontoblasts. Among Class I HDACs, HDAC-1 showed high expression in postnatal teeth, notably in ameloblasts and odontoblasts. HDAC-2 and -3 had extremely low expression in the rat dentine-pulp complex. Significant increases in acetylation were noted during DPC mineralisation processes, while trimethylation H3K9 and H3K27 marks decreased, and the HDAC-inhibitor suberoylanilide hydroxamic acid (SAHA) enhanced H3K27me3. These results highlight a dynamic alteration in histone acetylation during mineralisation and indicate the relevance of Class II HDAC expression in tooth development and regenerative processes.
Topics: Animals; Acetylation; Rats; Histone Deacetylases; Dentinogenesis; Dentin; Dental Pulp; Protein Processing, Post-Translational; Histones; Molar; Odontoblasts; Male
PubMed: 38928274
DOI: 10.3390/ijms25126569 -
International Journal of Hyperthermia :... 2024Dentin hypersensitivity (DH) is a prevalent condition, but long-term effective treatments are scarce. Differentiation of odontoblast-like cells is promising for inducing...
PURPOSE
Dentin hypersensitivity (DH) is a prevalent condition, but long-term effective treatments are scarce. Differentiation of odontoblast-like cells is promising for inducing tertiary dentinogenesis and ensuring sustained therapeutic efficacy against DH. This study examined the effects and mechanism of action of mild heat stress (MHS) on the differentiation of odontoblast-like MDPC-23 cells.
METHODS
We used a heating device to accurately control the temperature and duration, mimicking the thermal microenvironment of odontoblast-like cells. Using this device, the effects of MHS on cell viability and differentiation were examined. Cell viability was assessed using the MTT assay. The expression and nucleoplasmic ratio of the yes-associated protein (YAP) were examined by western blotting and immunofluorescence. The gene expression levels of heat shock proteins (HSPs) and dentin matrix protein-1 (DMP1) were measured using qPCR. Dentin sialophosphoprotein (DSPP) expression was evaluated using immunofluorescence and immunoblotting. Verteporfin was used to inhibit YAP activity.
RESULTS
Mild heat stress (MHS) enhanced the odontoblast differentiation of MDPC-23 cells while maintaining cell viability. MHS also increased YAP activity, as well as the levels of HSP25 mRNA, HSP70 mRNA, HSP90α mRNA, DMP1 mRNA, and DSPP protein. However, after YAP inhibition, both cell viability and the levels of HSP90α mRNA, DMP1 mRNA, and DSPP protein were reduced.
CONCLUSION
YAP plays a crucial role in maintaining cell viability and promoting odontoblast differentiation of MDPC-23 cells under MHS. Consequently, MHS is a potential therapeutic strategy for DH, and boosting YAP activity could be beneficial for maintaining cell viability and promoting odontoblast differentiation.
Topics: Odontoblasts; Cell Differentiation; Heat-Shock Response; Animals; YAP-Signaling Proteins; Mice; Cell Line; Adaptor Proteins, Signal Transducing; Cell Survival
PubMed: 38925872
DOI: 10.1080/02656736.2024.2369749 -
Biomedical Reports Aug 2024At low medically-relevant concentrations, ozone serves as an oxidant with a wide spectrum of antimicrobial activity and the ability to promote healing and reduce... (Review)
Review
At low medically-relevant concentrations, ozone serves as an oxidant with a wide spectrum of antimicrobial activity and the ability to promote healing and reduce inflammation. Despite providing therapeutic benefits in a range of diseases, certain adverse effects and contraindications of ozone treatment must be considered. These are primarily related to toxicity from inhalation and systemic types of administration and can be avoided by following relevant guidelines and recommendations. Ozone therapy has been implemented in a number of fields of dentistry and the most commonly used formulations for the oral cavity are gaseous ozone, ozonized water and ozonized oil. The biological mechanisms underlying the molecular effects of ozone have been increasingly reported, but currently remain largely unknown. The aim of the present review was to provide an overview of the mechanisms involved in ozone interaction with dental tissues. The present review focused on relevant evidence regarding the effect of ozone on dental tissues, including periodontal structures, dental cells, enamel and dentine, considering studies in addition to animal and human studies. A variety of biological mechanisms acting through multiple biochemical target pathways were reported to be responsible for the therapeutic effects of ozone. The main beneficial effects of ozone occurred in the following domains: antimicrobial activity, remineralization and microstructural changes of hard dental tissues, immunomodulation and biostimulation of dental and periodontal cells. Additional research could provide further insights into the use of ozone, increase its use for broader clinical applications and assist in the selection of targeted protocols.
PubMed: 38912169
DOI: 10.3892/br.2024.1803 -
International Journal of Molecular... May 2024It is remarkable how teeth maintain their healthy condition under exceptionally high levels of mechanical loading. This suggests the presence of inherent mechanical... (Review)
Review
It is remarkable how teeth maintain their healthy condition under exceptionally high levels of mechanical loading. This suggests the presence of inherent mechanical adaptation mechanisms within their structure to counter constant stress. Dentin, situated between enamel and pulp, plays a crucial role in mechanically supporting tooth function. Its intermediate stiffness and viscoelastic properties, attributed to its mineralized, nanofibrous extracellular matrix, provide flexibility, strength, and rigidity, enabling it to withstand mechanical loading without fracturing. Moreover, dentin's unique architectural features, such as odontoblast processes within dentinal tubules and spatial compartmentalization between odontoblasts in dentin and sensory neurons in pulp, contribute to a distinctive sensory perception of external stimuli while acting as a defensive barrier for the dentin-pulp complex. Since dentin's architecture governs its functions in nociception and repair in response to mechanical stimuli, understanding dentin mechanobiology is crucial for developing treatments for pain management in dentin-associated diseases and dentin-pulp regeneration. This review discusses how dentin's physical features regulate mechano-sensing, focusing on mechano-sensitive ion channels. Additionally, we explore advanced in vitro platforms that mimic dentin's physical features, providing deeper insights into fundamental mechanobiological phenomena and laying the groundwork for effective mechano-therapeutic strategies for dentinal diseases.
Topics: Dentin; Humans; Animals; Odontoblasts; Mechanotransduction, Cellular; Biomechanical Phenomena; Dental Pulp; Extracellular Matrix
PubMed: 38891829
DOI: 10.3390/ijms25115642 -
The Saudi Dental Journal Jun 2024Dental tissue engineering is an alternative procedure for restoring damaged dental tissues. Adipose-derived stem cells are a new source of cells for regenerative...
De novo regeneration of dentin pulp complex mediated by Adipose derived stem cells in an immunodeficient albino rat model (Histological, histochemical and scanning electron microscopic Study).
BACKGROUND
Dental tissue engineering is an alternative procedure for restoring damaged dental tissues. Adipose-derived stem cells are a new source of cells for regenerative endodontics in combination with scaffold materials. The descriptive data about this regenerative process is still insufficient.
OBJECTIVE
To evaluate the regenerative potential of Adipose-derived stem cells using a self-assembling polypeptide scaffold for the dentin-pulp complex in an emptied root canal space.
MATERIAL AND METHODS
40 root segments of human single-rooted teeth were transplanted into the albino rats' dorsal subcutaneous tissue. Root segments were divided into two groups: group I contained only a self-assembling polypeptide scaffold, and group II contained fluorescent-labeled Adipose-derived stem cells embedded in a self-assembling polypeptide scaffold. The newly formed tissues were assessed on the 60 and 90 days post-transplantation using routine histological examination, Masson trichrome staining, and scanning electron microscopy.
RESULTS
Group I showed granulation tissue without any signs of predentin formation or odontoblast-like cells. Group II revealed the presence of predentin tissue along the dentin margin, with arranged odontoblast-like cells. An organized connective tissue with abundant vasculature and calcific masses was observed in the pulp space.
CONCLUSION
Adipose-derived stem cells can be considered as alternative stem cells for regenerating the dentin-pulp complex. Dentin pulp complex regeneration utilizing a self-assembling polypeptide scaffold alone would not yield successful results.
PubMed: 38883895
DOI: 10.1016/j.sdentj.2024.03.020 -
The Saudi Dental Journal Jun 2024Despite that, the odontoblasts of the dental pulp are considered a terminally differentiated type of cell. We were interested in investigating if they express any...
Despite that, the odontoblasts of the dental pulp are considered a terminally differentiated type of cell. We were interested in investigating if they express any embryonic, mesenchymal, or neural stem cell markers, along with other differentiation markers they were reported to express previously. : An immunohistochemistry study was performed on wisdom teeth extracted from healthy donors aged between 17 and 19 for dental reasons. Nine markers were tested: c-Myc, SOX2, MCAM, CD73, NCAM1, STRO1, osteocalcin, S100, and Thy1. : Odontoblasts expressed the following markers: embryonic stem cell markers SOX2, c-Myc, mesenchymal stem cell marker MCAM, the neural differentiation marker S100, and the osteogenic differentiation marker osteocalcin. Odontoblasts did not express the following markers: mesenchymal stem cell markers CD73, STRO1, Thy1, and neural stem cell marker NCAM1. : These findings suggest that odontoblasts' expression of these stem cell markers may enable them to dedifferentiate under certain conditions. Further investigation is needed into whether dental materials could induce such dedifferentiation for functional dentin regeneration.
PubMed: 38883894
DOI: 10.1016/j.sdentj.2024.03.011 -
Scientific Reports Jun 2024Notum is a direct target of Wnt/β-catenin signaling and plays a crucial role as a Wnt inhibitor within a negative feedback loop. In the tooth, Notum is known to be...
Notum is a direct target of Wnt/β-catenin signaling and plays a crucial role as a Wnt inhibitor within a negative feedback loop. In the tooth, Notum is known to be expressed in odontoblasts, and severe dentin defects and irregular tooth roots have been reported in Notum-deficient mice. However, the precise expression pattern of Notum in early tooth development, and the role of Notum in crown and root patterns remain elusive. In the present study, we identified a novel Notum expression in primary enamel knot (EK), secondary EKs, and dental papilla during tooth development. Notum-deficient mice exhibited enlarged secondary EKs, resulting in broader cusp tips, altered cusp patterns, and reduced concavity in crown outline. These alterations in crown outline led to a reduction in cervical tongue length, thereby inducing root fusion in Notum-deficient mice. Overall, these results suggest that the secondary EK size, regulated by the Wnt/Notum negative feedback loop, has a significant impact on the patterns of crown and root during tooth morphogenesis.
Topics: Animals; Mice; Gene Expression Regulation, Developmental; Mice, Knockout; Molar; Odontogenesis; Receptors, G-Protein-Coupled; Tooth Crown; Tooth Root; Wnt Signaling Pathway
PubMed: 38871845
DOI: 10.1038/s41598-024-64340-w -
Clinical Oral Investigations May 2024Mechano-sensitive odontoblast cells, which sense mechanical loading and various stresses in the tooth structure, synthesize early signaling molecules such as... (Comparative Study)
Comparative Study
The importance of mechanosensitive cell mediated prostaglandin and nitric oxide synthesis in the pathogenesis of apical periodontitis: comparative with chronic periodontitis.
OBJECTIVES
Mechano-sensitive odontoblast cells, which sense mechanical loading and various stresses in the tooth structure, synthesize early signaling molecules such as prostaglandin E2 (PGE2) and nitric oxide (NO) as an adaptive response. It is thought that these synthesized molecules can be used for the diagnosis and treatment of periodontal and periapical diseases. The aim of this study was to investigate the relationship between the severity of apical periodontitis (AP) and chronic periodontitis (CP) and serum (s) TNF-α, IL-10, PGE2 and NO levels, as well as PGE2 and NO levels in gingival crevicular fluid (GCF) samples.
MATERIALS & METHODS
A total of 185 subjects were divided into three categories: AP group (n = 85), CP group (n = 50) and healthy control group (n = 50). The AP group was divided into 3 subgroups according to abscess scoring (AS-PAI 1, 2 and 3) based on the periapical index. The CP group was divided into 4 subgroups according to the periodontitis staging system (PSS1, 2,3 and 4). After recording the demographic and clinical characteristics of all participants, serum (s) and gingival crevicular fluid (GCF) samples were taken. TNF-α, IL-10, PGE2 and NO levels were measured in these samples.
RESULTS
Unlike serum measurements (sTNF-α, sIL-10, sNO and sPGE2), GCF-NO and GCF-PGE levels of the AP group were significantly higher than the control group in relation to abscess formation (54.4 ± 56.3 vs. 22.5 ± 12.6 µmol/mL, p < 0.001 and 100 ± 98 vs. 41 ± 28 ng/L, p < 0.001, respectively). Confirming this, the GCF-NO and GCF-PGE levels of the AS-PAI 1 group, in which abscesses have not yet formed, were found to be lower than those in AS-PAI 2 and 3, which are characterized by abscess formation [(16.7(3.7-117.8), 32.9(11.8-212.8) and 36.9(4.3-251.6) µmol/mL, p = 0,0131; 46.0(31.4-120.0), 69.6(40.3-424.2) and 74.4(32.1-471.0) ng/L, p = 0,0020, respectively]. Consistent with the increase in PSS, the levels of sTNF [29.8 (8.2-105.5) vs. 16.7(6.3-37.9) pg/mL, p < 0.001], sIL-10 [542(106-1326) vs. 190(69-411) pg/mL, p < 0.001], sNO [182.1(36.3-437) vs. 57.0(15.9-196) µmol/mL, p < 0.001], sPGE2 [344(82-1298) vs. 100(35-1178) ng/L, p < 0.001], GCF-NO [58.9 ± 33.6 vs. 22.5 ± 12.6 ng/L, p < 0.001] and GCF-PGE2 [ 99(37-365) vs. 30(13-119), p < 0.001] in the CP group were higher than the control group. Comparison ROC analysis revealed that the GCF-PGE2 test had the best diagnostic value for both AP and CP (sensitivity: 94.1 and 88.0; specificity: 64.0 and 78.0, respectively; p < 0.001).
CONCLUSIONS
GCF-PE2 and GCF-NO have high diagnostic value in the determination of AP and CP, and can be selected as targets to guide treatment. In addition, the measurements of PGE2 and NO in GCF can be used as an important predictor of pulpal necrosis leading to abscess in patients with AP.
CLINICAL RELEVANCE
In this article, it is reported that syntheses of early signaling molecules such as PGE2 and NO can be used for the diagnosis and treatment target of periapical and periodontal infections.
Topics: Humans; Periapical Periodontitis; Male; Female; Chronic Periodontitis; Nitric Oxide; Gingival Crevicular Fluid; Adult; Dinoprostone; Interleukin-10; Tumor Necrosis Factor-alpha; Middle Aged; Enzyme-Linked Immunosorbent Assay; Case-Control Studies
PubMed: 38795217
DOI: 10.1007/s00784-024-05721-3 -
BMC Oral Health May 2024This study aimed to evaluate dentin wear and biological performance of desensitizing materials.
BACKGROUND
This study aimed to evaluate dentin wear and biological performance of desensitizing materials.
METHODS
Seventy bovine root dentin blocks were sectioned. Half of the surface of each specimen was untreated (control) and the other half was immersed in EDTA and treated with the following desensitizing materials: placebo varnish (PLA), fluoride varnish (FLU), sodium fluoride (NaF) varnish + sodium trimetaphosphate (TMP), universal adhesive (SBU), S-PRG varnish (SPRG), biosilicate (BIOS), and amelotin solution (AMTN). After application, the specimens were submitted to an erosive-abrasive challenge and the wear analyzed by optical profilometer. Serial dilutions of extracts obtained from the culture medium containing discs impregnated with those desensitizers were applied on fibroblasts and odontoblasts-like cells cultures. Cytotoxicity and production of total protein (TP) by colorimetric assays were determined after 24 h. Data were statistically analyzed using Kruskal-Wallis, Dunn's, One-way ANOVA and Tukey tests (p ≤ 0.05).
RESULTS
No dentin wear was observed only for SBU. The lowest dentin wear was observed for AMTN and TMP. Cell viability was significantly reduced after treatment with undiluted extracts of PLA, FLU, TMP and SBU in fibroblasts and TMP and SBU in odontoblast-like cells. SPRG, BIOS and AMTN were cytocompatible at all dilutions tested. Considering TP results, no statistical difference was observed among the groups and high levels for TP were observed after TMP and FLU treatments.
CONCLUSIONS
Universal adhesive system may protect dentin with opened tubules from wear after challenge. Extracts of adhesive and fluoride varnishes presented cytotoxic mainly on fibroblasts. The enamel protein may be a future alternative to treat dentin with opened tubules because it may cause low wear under erosive-abrasive challenge with low cytotoxic effects.
Topics: Animals; Cattle; Dentin Desensitizing Agents; Sodium Fluoride; Dentin; Fluorides, Topical; Fibroblasts; Cell Survival; Tooth Wear; Materials Testing; Polyphosphates
PubMed: 38789946
DOI: 10.1186/s12903-024-04373-9 -
Genes & Diseases Sep 2024
PubMed: 38756354
DOI: 10.1016/j.gendis.2023.101103