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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 -
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 -
Basic and Clinical Neuroscience 2023Published data obtained from in vitro and in vivo studies was reviewed systematically and analyzed critically to evaluate the effect of oral cavity-derived stem cells... (Review)
Review
INTRODUCTION
Published data obtained from in vitro and in vivo studies was reviewed systematically and analyzed critically to evaluate the effect of oral cavity-derived stem cells (OCDSCs) on the recovery or therapy of neurodegenerative diseases (NDs), such as Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS), Huntington (HD) diseases, and Parkinson disease (PD).
METHODS
An electronic search was accomplished. References of included articles were also manually searched. Studies were critically evaluated for suitability against the inclusion/exclusion criteria and the data was extracted. Bias risk evaluation of the studies and evidence synthesis were conducted.
RESULTS
A total of 14 in vivo and 10 in vitro studies met the inclusion criteria. PD was induced in 10 in vivo and 7 in vitro studies, while AD was induced in 2 in vivo and 4 in vitro studies. Two studies (1 in vitro and 1 in vivo) evaluated ALS disease and 1 in vivo study evaluated HD. Moderate evidence was found for in vitro studies reporting the positive effect of OCDSCs on PD or AD recovery. Strong evidence was found for in vivo studies in which PD animal models were used; meanwhile, moderate evidence was found for the impact of OCDSCs on AD recovery. Limited evidence was found for in vivo studies evaluating HD and ALS.
CONCLUSION
Although studies reported favorable data regarding the OCDSCs on NDs, they presented a considerable risk of bias. Because of heterogeneous study characteristics, the current study recommends improving standardized methods to evaluate the therapeutic effects of OCDSCs on the NDs.
PubMed: 38628839
DOI: 10.32598/bcn.2021.2892.1 -
Regenerative Therapy Dec 2024The objective of the present study was to investigate whether NOD-like receptor family pyrin domain-containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes...
OBJECTIVES
The objective of the present study was to investigate whether NOD-like receptor family pyrin domain-containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes pathways were involved in an experimental model of fibroblast activation named nemosis, which was used to mimic circumstances without bacteria stimulation.
METHODS
Nemosis of human dental pulp fibroblast (DPFs) was induced by three-dimensional culture in U-shaped 96-well plates and investigated by scanning electron microscopy (SEM). DPFs monolayers were used as control. Annexin V-FITC/7-AAD apoptosis assay was performed on the DPFs spheroids by flowcytometry. Caspase-1 activity detection assay was conducted on the DPFs spheroids. Quantitative real-time polymerase chain reaction (qRT-PCR), cytokine measurements, Western blot and the effect of COX-2 inhibitor on spheroids was studied.
RESULTS
SEM study observed human dental pulp fibroblast clusters and cell membranes damage on the surface of DPFs spheroids. The percentages of necrotic cells from DPFs spheroids gradually increased as the incubation time increased. A statistically significant increase in caspase-1 activity was observed after DPFs spheroids formation. DPFs spheroids displayed significant amounts of NLRP3, AIM2 mRNA and protein expression, caspase-1 mRNA expression and cleaved Caspase-1 protein expression and high IL-1β concentrations ( < 0.05) than DPFs monolayers. Specific COX-2 inhibitor (NS-398) decreased NLRP3 mRNA and protein expression, cleaved Caspase-1 protein expression, Caspase-1 activity and IL-1β mRNA expression and IL-1β concentrations ( < 0.05). However, Specific COX-2 inhibitor had no impact on AIM2 mRNA and protein expression, caspase-1 mRNA expression and pro-Caspase-1 protein expression.
CONCLUSIONS
In conclusion, clustering human DPFs spontaneously activated NLRP3 and AIM2 inflammasomes and induced IL-1β secretion which could be partially attenuated by COX-2 inhibitor. Thus, nemosis could become a powerful model for studying mechanisms underlying aseptic pulpitis.
PubMed: 38487102
DOI: 10.1016/j.reth.2024.02.010 -
Journal of Translational Medicine Jan 2024Epigenetic factors influence the odontogenic differentiation of dental pulp stem cells and play indispensable roles during tooth development. Some microRNAs can...
BACKGROUND
Epigenetic factors influence the odontogenic differentiation of dental pulp stem cells and play indispensable roles during tooth development. Some microRNAs can epigenetically regulate other epigenetic factors like DNA methyltransferases and histone modification enzymes, functioning as epigenetic-microRNAs. In our previous study, microarray analysis suggested microRNA-93-5p (miR-93-5p) was differentially expressed during the bell stage in human tooth germ. Prediction tools indicated that miR-93-5p may target lysine-specific demethylase 6B (KDM6B). Therefore, we explored the role of miR-93-5p as an epi-miRNA in tooth development and further investigated the underlying mechanisms of miR-93-5p in regulating odontogenic differentiation and dentin formation.
METHODS
The expression pattern of miR-93-5p and KDM6B of dental pulp stem cells (DPSCs) was examined during tooth development and odontogenic differentiation. Dual luciferase reporter and ChIP-qPCR assay were used to validate the target and downstream regulatory genes of miR-93-5p in human DPSCs (hDPSCs). Histological analyses and qPCR assays were conducted for investigating the effects of miR-93-5p mimic and inhibitor on odontogenic differentiation of hDPSCs. A pulpotomy rat model was further established, microCT and histological analyses were performed to explore the effects of KDM6B-overexpression and miR-93-5p inhibition on the formation of tertiary dentin.
RESULTS
The expression level of miR-93-5p decreased as odontoblast differentiated, in parallel with elevated expression of histone demethylase KDM6B. In hDPSCs, miR-93-5p overexpression inhibited the odontogenic differentiation and vice versa. MiR-93-5p targeted 3' untranslated region (UTR) of KDM6B, thereby inhibiting its protein translation. Furthermore, KDM6B bound the promoter region of BMP2 to demethylate H3K27me3 marks and thus upregulated BMP2 transcription. In the rat pulpotomy model, KDM6B-overexpression or miR-93-5p inhibition suppressed H3K27me3 level in DPSCs and consequently promoted the formation of tertiary dentin.
CONCLUSIONS
MiR-93-5p targets epigenetic regulator KDM6B and regulates H3K27me3 marks on BMP2 promoters, thus modulating the odontogenic differentiation of DPSCs and dentin formation.
Topics: Humans; Rats; Animals; Histones; Stem Cells; Cell Differentiation; MicroRNAs; Dentin; Cells, Cultured; Jumonji Domain-Containing Histone Demethylases
PubMed: 38218880
DOI: 10.1186/s12967-024-04862-z -
Cureus Nov 2023Pulpectomy has always been a treatment choice when irreversible damage to the pulpal and periapical tissues occurs, but in a pediatric patient, expecting cooperation and... (Review)
Review
Pulpectomy has always been a treatment choice when irreversible damage to the pulpal and periapical tissues occurs, but in a pediatric patient, expecting cooperation and adequate chair side time is a huge task as they fear the dentists and the instruments. Hence, it was required that there come an advanced treatment protocol that helps overcome the drawbacks of the existing treatment modality. A new therapeutic strategy called lesion sterilization and tissue repair (LSTR) is revolutionizing how dental lesions are treated today. Through a non-invasive antimicrobial treatment, this cutting-edge method seeks to halt the spread of carious lesions while encouraging tissue repair and regeneration. In LSTR, the infected tooth tissues are treated directly with a special antimicrobial combination of antibiotics, reducing agents, and disinfectants. Through the elimination of the microorganisms that cause dental decay and the creation of an environment that is favorable for natural tissue healing, this intervention targets the microbial etiology. This article mainly focuses on using antibiotics as a treatment modality in a tooth affected by caries and where the pulp and periradicular tissues are irreversibly inflamed. Pulpectomy has always been the most practiced technique, but in children, due to the lack of cooperation during the treatment and harm to the underlying developing tooth bud, a less invasive protocol had to be used, which is LSTR. This review delves into the basic ideas, techniques, and clinical applications of lesion sterilization and tissue restoration to look at its various aspects. This review clarifies the effectiveness and safety of LSTR in controlling diverse dental diseases, ranging from early-stage caries to deep dentin infections, by critically assessing previous study findings. It also emphasizes LSTR's ability to preserve vital tooth pulp, obviating the need for invasive and frequently uncomfortable endodontic operations. The review advocates for integrating LSTR into contemporary dental practices, showcasing its potential to transform the landscape of oral healthcare. By providing a comprehensive overview of this innovative technique, this review encourages further research and clinical implementation, heralding a new era in dentistry focused on preservation, regeneration, and enhanced patient well-being.
PubMed: 38054133
DOI: 10.7759/cureus.48218 -
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 -
Bone Research Jan 2024Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge, as chronic local inflammation can largely impair...
Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge, as chronic local inflammation can largely impair bone healing. Here, we used magnesium silicate nanospheres (MSNs) to load microRNA-146a-5p (miR-146a) to fabricate a nanobiomaterial, MSN+miR-146a, which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells (hDPSCs). In addition, miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages (BMMs) under lipopolysaccharide (LPS) stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6 (TRAF6), and MSNs could simultaneously promote M2 polarization of BMMs. MiR-146a was also found to inhibit osteoclast formation. Finally, the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring hydrogel. Collectively, the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oral-maxillofacial bone defects.
Topics: Mice; Animals; Humans; MicroRNAs; Osteogenesis; Nanospheres; Inflammation; Bone Regeneration; Silicates; Magnesium Silicates
PubMed: 38221522
DOI: 10.1038/s41413-023-00299-0 -
International Journal of Molecular... Aug 2023Three-dimensional (3D) bioprinting is a unique combination of technological advances in 3D printing and tissue engineering. It has emerged as a promising approach to... (Review)
Review
Three-dimensional (3D) bioprinting is a unique combination of technological advances in 3D printing and tissue engineering. It has emerged as a promising approach to address the dilemma in current dental treatments faced by clinicians in order to repair or replace injured and diseased tissues. The exploration of 3D bioprinting technology provides high reproducibility and precise control of the bioink containing the desired cells and biomaterial over the architectural and dimensional features of the scaffolds in fabricating functional tissue constructs that are specific to the patient treatment need. In recent years, the dental applications of different 3D bioprinting techniques, types of novel bioinks, and the types of cells used have been extensively explored. Most of the findings noted significant challenges compared to the non-biological 3D printing approach in constructing the bioscaffolds that mimic native tissues. Hence, this review focuses solely on the implementation of 3D bioprinting techniques and strategies based on cell-laden bioinks. It discusses the in vitro applications of 3D-bioprinted scaffolds on cell viabilities, cell functionalities, differentiation ability, and expression of the markers as well as the in vivo evaluations of the implanted bioscaffolds on the animal models for bone, periodontal, dentin, and pulp tissue regeneration. Finally, it outlines some perspectives for future developments in dental applications.
Topics: Animals; Reproducibility of Results; Biocompatible Materials; Bioprinting; Cell Differentiation; Cell Survival
PubMed: 37629064
DOI: 10.3390/ijms241612881 -
Advanced Science (Weinheim,... Aug 2023Dental pulp stem cells (DPSCs), characterized by easy availability, multi-lineage differentiation ability, and high proliferation ability, are ideal seed cells for...
Dental pulp stem cells (DPSCs), characterized by easy availability, multi-lineage differentiation ability, and high proliferation ability, are ideal seed cells for cartilage tissue engineering. However, the epigenetic mechanism underlying chondrogenesis in DPSCs remains elusive. Herein, it is demonstrated that KDM3A and G9A, an antagonistic pair of histone-modifying enzymes, bidirectionally regulate the chondrogenic differentiation of DPSCs by controlling SOX9 (sex-determining region Y-type high-mobility group box protein 9) degradation through lysine methylation. Transcriptomics analysis reveals that KDM3A is significantly upregulated during the chondrogenic differentiation of DPSCs. In vitro and in vivo functional analyses further indicate that KDM3A promotes chondrogenesis in DPSCs by boosting the SOX9 protein level, while G9A hinders the chondrogenic differentiation of DPSCs by reducing the SOX9 protein level. Furthermore, mechanistic studies indicate that KDM3A attenuates the ubiquitination of SOX9 by demethylating lysine (K) 68 residue, which in turn enhances SOX9 stability. Reciprocally, G9A facilitates SOX9 degradation by methylating K68 residue to increase the ubiquitination of SOX9. Meanwhile, BIX-01294 as a highly specific G9A inhibitor significantly induces the chondrogenic differentiation of DPSCs. These findings provide a theoretical basis to ameliorate the clinical use of DPSCs in cartilage tissue-engineering therapies.
Topics: Lysine; Chondrogenesis; Methylation; Dental Pulp; Cells, Cultured; Stem Cells; Cell Differentiation
PubMed: 37386801
DOI: 10.1002/advs.202206757