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Cureus Oct 2023The pathophysiology of calcified dental pulp is considered to be comparable to that of calcified atheroma in the artery. These calcified masses are small nodular which... (Review)
Review
The pathophysiology of calcified dental pulp is considered to be comparable to that of calcified atheroma in the artery. These calcified masses are small nodular which is seen more often in the coronal pulp region than in the radicular pulp. This is generally more common in the elderly population and usually corresponds to increasing age. Calcifications are also found in the brain, breast, arteries, and kidneys. There is a link between pulp calcification and cardiovascular problems. It is commonly assumed that individuals suffering from cardiovascular diseases have a higher risk of calcification in the pulp. The use of radiography as a quick means of detecting cardiovascular disease is possible. The pulp calcification process is usually triggered by the osteoblastic process. The process is identified by the presence of an osteoid matrix, which is built down by odontoblast cells in the pulp's peripheral portions, culminating in the production of tissue that is comparable to dentine. This review will look at pulp calcifications from all angles, including their mechanism, clinical considerations, radiographic features, and management, and also to determine if there is a link between pulp calcification and cardiovascular problems.
PubMed: 38021616
DOI: 10.7759/cureus.47258 -
Frontiers in Cell and Developmental... 2023The circadian clock plays a critical role in dentomaxillofacial development. Tooth biomineralization is characterized by the circadian clock; however, the mechanisms...
The circadian clock plays a critical role in dentomaxillofacial development. Tooth biomineralization is characterized by the circadian clock; however, the mechanisms underlying the coordination of circadian rhythms with tooth development and biomineralization remain unclear. The p75 neurotrophin receptor (p75NTR) is a clock factor that regulates the oscillatory components of the circadian rhythm. This study aims to investigate the impact of p75NTR on the rhythmic mineralization of teeth and elucidate its underlying molecular mechanisms. We generated p75NTR knockout mice to examine the effects of p75NTR deficiency on tooth mineralization. Ectomesenchymal stem cells (EMSCs), derived from mouse tooth germs, were used for experiments. Results showed a reduction in tooth mineral density and daily mineralization rate in p75NTR knockout mice. Deletion of p75NTR decreased the expression of DMP1, DSPP, RUNX2, and ALP in tooth germ. Odontogenic differentiation and mineralization of EMSCs were activated by p75NTR. Histological results demonstrated predominant detection of p75NTR protein in odontoblasts and stratum intermedium cells during rapid formation phases of dental hard tissue. The mRNA expression of exhibited circadian variations in tooth germs and EMSCs, consistent with the expression patterns of the core clock genes and . The upregulation of BMAL1/CLOCK expression by p75NTR positively regulated the mineralization ability of EMSCs, whereas BMAL1 and CLOCK exerted a negative feedback regulation on p75NTR by inhibiting its promoter activity. Our findings suggest that p75NTR is necessary to maintain normal tooth biomineralization. Odontogenic differentiation and mineralization of EMSCs is regulated by the p75NTR-BMAL1/CLOCK signaling axis. These findings offer valuable insights into the associations between circadian rhythms, tooth development, and biomineralization.
PubMed: 38020910
DOI: 10.3389/fcell.2023.1283878 -
Biomedical Research (Tokyo, Japan) 2023This study aimed to explore the potential roles of fractalkine/CX3CR1, primarily expressed in vascular endothelial cells and has recently been identified in dental pulp...
This study aimed to explore the potential roles of fractalkine/CX3CR1, primarily expressed in vascular endothelial cells and has recently been identified in dental pulp cells at sites of pulp tissue inflammation, not only in inflammation but also in pulp hard tissue formation. To this end, cultured human dental pulp cells were grown in 10% FBS-supplemented α-MEM. Fractalkine was introduced to the culture, and COX-2 and dentin sialophosphoprotein (DSPP) expression levels were evaluated via western blotting. Real-time PCR was used to examine BMP-2 and Osterix mRNA expression. Calcified nodule formation was evaluated with Alizarin red staining. Results revealed that fractalkine increased COX-2 protein expression, calcified nodule formation, and BMP-2 and Osterix mRNA expression in a concentration- and time-dependent manner. DSPP protein expression also increased upon fractalkine addition. This effect of fractalkine on expression of DSPP protein was inhibited in the presence of the CX3CR1 inhibiter ADZ8797. In conclusion, our findings suggest a dual role for fractalkine in promoting pulp inflammation via COX-2 production and contributing to pulp hard tissue formation by stimulating the expression of hard tissue formation markers.
Topics: Humans; Cell Differentiation; Cells, Cultured; Chemokine CX3CL1; Cyclooxygenase 2; Dental Pulp; Endothelial Cells; Extracellular Matrix Proteins; Inflammation; Odontoblasts; RNA, Messenger
PubMed: 38008424
DOI: 10.2220/biomedres.44.257 -
International Journal of Oral Science Nov 2023Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation. The initiation of Hertwig's epithelial root sheath (HERS) induces... (Review)
Review
Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation. The initiation of Hertwig's epithelial root sheath (HERS) induces odontoblast differentiation and the subsequent radicular dentin deposition. Precisely controlled signaling pathways modulate the behaviors of HERS and the fates of dental mesenchymal stem cells (DMSCs). Disruptions in these pathways lead to defects in root development, such as shortened roots and furcation abnormalities. Advances in dental stem cells, biomaterials, and bioprinting show immense promise for bioengineered tooth root regeneration. However, replicating the developmental intricacies of odontogenesis has not been resolved in clinical treatment and remains a major challenge in this field. Ongoing research focusing on the mechanisms of root development, advanced biomaterials, and manufacturing techniques will enable next-generation biological root regeneration that restores the physiological structure and function of the tooth root. This review summarizes recent discoveries in the underlying mechanisms governing root ontogeny and discusses some recent key findings in developing of new biologically based dental therapies.
Topics: Female; Humans; Tooth Root; Odontogenesis; Epithelial Cells; Cell Differentiation; Biocompatible Materials
PubMed: 38001110
DOI: 10.1038/s41368-023-00258-9 -
Biomimetics (Basel, Switzerland) Oct 2023Assessing the biocompatibility of endodontic root-end filling materials through cell line responses is both essential and of utmost importance. This study aimed to the...
Assessing the biocompatibility of endodontic root-end filling materials through cell line responses is both essential and of utmost importance. This study aimed to the cytotoxicity of the type of cell death through apoptosis and autophagy, and odontoblast cell-like differentiation effects of MTA, zinc oxide-eugenol, and two experimental Portland cements modified with bismuth (Portland Bi) and barium (Portland Ba) on primary cell cultures. Material and methods: The cells corresponded to human periodontal ligament and gingival fibroblasts (HPLF, HGF), human pulp cells (HPC), and human squamous carcinoma cells from three different patients (HSC-2, -3, -4). The cements were inoculcated in different concentrations for cytotoxicity evaluation, DNA fragmentation in electrophoresis, apoptosis caspase activation, and autophagy antigen reaction, odontoblast-like cells were differentiated and tested for mineral deposition. The data were subject to a non-parametric test. Results: All cements caused a dose-dependent reduction in cell viability. Contact with zinc oxide-eugenol induced neither DNA fragmentation nor apoptotic caspase-3 activation and autophagy inhibitors (3-methyladenine, bafilomycin). Portland Bi accelerated significantly ( < 0.05) the differentiation of odontoblast-like cells. Within the limitation of this study, it was concluded that Portland cement with bismuth exhibits cytocompatibility and promotes odontoblast-like cell differentiation. This research contributes valuable insights into biocompatibility, suggesting its potential use in endodontic repair and biomimetic remineralization.
PubMed: 37999155
DOI: 10.3390/biomimetics8070514 -
Journal of Functional Biomaterials Nov 2023In recent years, alternative pulpal therapies targeting dentinogenesis signaling pathways using different peptides have been investigated. The aim of this study was to...
UNLABELLED
In recent years, alternative pulpal therapies targeting dentinogenesis signaling pathways using different peptides have been investigated. The aim of this study was to verify the effectiveness of poly(aspartic acid), pAsp, in dentin regeneration using an animal model.
METHODS
Mechanical pulp exposure was performed in the upper molars of 56 Wistar rats, randomly divided as follows (n = 14): control (no treatment); MTA group-pulp capping with mineral trioxide aggregate (MTA Angelus); pAsp group-application of 20 μL of pAsp solution (25 mg·mL); MTA+pAsp group-application of MTA mixed with pAsp (5:1 by mass). Animals were euthanized after 7 or 21 days. Histological sections were submitted to hematoxylin-eosin and Brown and Brenn staining and immunohistochemical analysis for osteopontin (OPN) and dentin matrix protein 1 (DMP 1).
RESULTS
At 7 days, an acute inflammatory infiltrate and the presence of disorganized mineralized tissue were observed in all groups. At 21 days, the quality and thickness of the reparative dentin in treated groups were superior to the control, and bacterial contamination was observed in two MTA-pAsp specimens. While all treated groups showed intense immunostaining for OPN at 21 days, only the pAsp group expressed DMP 1, indicating the presence of fully differentiated odontoblast-like cells.
CONCLUSION
Poly(aspartic) acid promoted dentin regeneration in rat molars in the absence of an additional calcium source and may be an alternative to MTA as a pulp-capping agent.
PubMed: 37998106
DOI: 10.3390/jfb14110537 -
Frontiers in Cell and Developmental... 2023Heparan sulfate proteoglycans (HSPGs) surround the surface of odontoblasts, and their modification affects their affinity for Wnt ligands. This study proposes applying...
On-demand chlorine dioxide solution enhances odontoblast differentiation through desulfation of cell surface heparan sulfate proteoglycan and subsequent activation of canonical Wnt signaling.
Heparan sulfate proteoglycans (HSPGs) surround the surface of odontoblasts, and their modification affects their affinity for Wnt ligands. This study proposes applying Matching Transformation System (MA-T), a novel chlorinated oxidant, to enhance dentinogenesis. MA-T treatment in odontoblasts decreased sulfation of HSPG and upregulated the expression of () and () via activation of canonical Wnt signaling . application of MA-T also enhanced dentin matrix formation in developing tooth explants. Reanalysis of a public single-cell RNA-seq dataset revealed significant Wnt activity in the odontoblast population, with enrichment for and . Silencing assays showed that and were redundant in inducing and mRNA expression. These Wnt ligands' expression was upregulated by MA-T treatment, and TCF/LEF binding sites are present in their promoters. Furthermore, the Wnt inhibitors Notum and Dkk1 were enriched in odontoblasts, and their expression was also upregulated by MA-T treatment, together suggesting autonomous maintenance of Wnt signaling in odontoblasts. This study provides evidence that MA-T activates dentinogenesis by modifying HSPG and through subsequent activation of Wnt signaling.
PubMed: 37954207
DOI: 10.3389/fcell.2023.1271455 -
Frontiers in Physiology 2023Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells that can differentiate into odontoblast-like cells and protect the pulp. The differentiation of DPSCs... (Review)
Review
Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells that can differentiate into odontoblast-like cells and protect the pulp. The differentiation of DPSCs can be influenced by biomaterials or growth factors that activate different signaling pathways or . In this review, we summarized six major pathways involved in the odontogenic differentiation of DPSCs, Wnt signaling pathways, Smad signaling pathways, MAPK signaling pathways, NF-kB signaling pathways, PI3K/AKT/mTOR signaling pathways, and Notch signaling pathways. Various factors can influence the odontogenic differentiation of DPSCs through one or more signaling pathways. By understanding the interactions between these signaling pathways, we can expand our knowledge of the mechanisms underlying the regeneration of the pulp-dentin complex.
PubMed: 37929208
DOI: 10.3389/fphys.2023.1272764 -
Journal of Functional Biomaterials Oct 2023The development of multifunctional materials has been expected in dentistry. This study investigated the effects of a novel universal bond containing a bioactive...
The development of multifunctional materials has been expected in dentistry. This study investigated the effects of a novel universal bond containing a bioactive monomer, calcium 4-methacryloxyethyl trimellitic acid (CMET), on odontoblast differentiation in vitro. Eluates from bioactive universal bond with CMET (BA (+), BA bond), bioactive universal bond without CMET (BA (-)), and Scotchbond Universal Plus adhesive (SC, 3M ESPE, USA) were added to the culture medium of the rat odontoblast-like cell line MDPC-23. Then, cell proliferation, differentiation, and mineralization were examined. Statistical analyses were performed using a one-way ANOVA and Tukey's HSDtest. The cell counting kit-8 assay and alkaline phosphatase (ALP) assay showed that cell proliferation and ALP were significantly higher in the 0.5% BA (+) group than in the other groups. In a real-time reverse-transcription polymerase chain reaction, mRNA expression of the odontogenic markers, dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1), was significantly higher in the 0.5% BA (+) group than in the BA (-) and SC groups. Calcific nodule formation in MDPC-23 cells was accelerated in the BA (+) group in a dose-dependent manner ( < 0.01); however, no such effect was observed in the BA (-) and SC groups. Thus, the BA bond shows excellent potential for dentin regeneration.
PubMed: 37888170
DOI: 10.3390/jfb14100506 -
Cells Oct 2023Regenerative therapies to replace cells and tissues damaged due to trauma and dental infections require temporal and spatial controlled recruitment and the...
Regenerative therapies to replace cells and tissues damaged due to trauma and dental infections require temporal and spatial controlled recruitment and the differentiation of progenitor/stem cells. However, increasing evidence shows microbial antigens can interfere with this process. Toll-like receptors (TLRs) are crucial in recognizing pathogen-associated molecular patterns. Stem cells of the apical papilla (SCAP) are required for normal dental development and are intimately involved in the reparative and regenerative capacity of developing teeth. We hypothesized that TLRs are expressed in SCAP and that the activation of TLR2/TLR4 or TLR3 by different ligands results in differential cellular fate, impacting their differentiation into a mineralizing phenotype. We found that most TLRs are expressed as detected by PCR except TLR7 and TLR8; exposure to heat-killed E. coli results in upregulating TLR2 and TLR4 and reducing mineralization capacity. In addition, bacterial exposure resulted in the upregulation of 11 genes, of which 9 were chemokines whose proteins were also upregulated and released, promoting in vitro macrophage migration. On the other hand, TLR3 activation resulted in increased proliferation and a dramatic inhibition of osteogenic and odontoblastic differentiation, which was reversed by inhibition or the knockdown of TLR3 expression. The profound effects of TLR activation resulting in different cell fates that are ligand and receptor-specific warrants further evaluation and represents an important therapeutic target to make regenerative approaches more predictable following dental infections.
Topics: Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptor 3; Regenerative Endodontics; Escherichia coli; Toll-Like Receptors; Stem Cells; Ligands
PubMed: 37887345
DOI: 10.3390/cells12202502