FoxO1 mediates odontoblast differentiation of hDPSCs via B cell‐derived ANGPTL1 in dental caries: A laboratory investigation

International Endodontic Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Abstract Aim Clinical and in vitro evidence indicates that chronic inflammatory responses initiated by dental caries can persist the pulp even after treatment, necessitating formation of reparative dentin to restore tissue homeostasis health. Human stem cells (hDPSCs) serve as crucial precursors this process. This study explores role B their secreted factor, Angiopoietin Like 1 (ANGPTL1), promoting hDPSCs differentiation into odontoblasts under carious conditions, with a particular focus on activation Forkhead box O1 (FoxO1). Methodology Single‐cell RNA sequencing (scRNA‐Seq) data from GEO database were analysed explore cellular interactions molecular mechanisms pulp. Immunofluorescence staining was used investigate expression patterns or hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds. The levels ANGPTL1 quantified using enzyme‐linked immunosorbent assay (ELISA). Odontoblast capacity assessed alkaline phosphatase activity, alizarin red S staining, western blotting analysis. overexpressed knocked down FoxO1 lentiviruses. regulatory interaction between DSPP promoter evaluated through dual‐luciferase reporter chromatin immunoprecipitation assay. Statistical analyses conducted Student's t ‐test one‐way analysis variance ( anova ) p ‐value <.05 considered statistically significant. Results scRNA‐Seq indicated significant increase Functional confirmed activated hDPSCs, enhancing odontoblast‐like cells. Blocking signalling specific antibody reduced expression, indicating link FoxO1. Overexpression promoted facilitated mineralized matrix formation. Mechanistic studies revealed directly binds promoter, thereby inducing its expression. Conclusions Our reveals novel mechanism which environment promotes odontoblast upregulating finding highlights potential therapeutic target for repair regeneration.

Language: Английский

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Three-dimensional matrix stiffness-based stem cell soil: Tri-Phase Biomechanical Structure promoted human dental pulp stem cells to achieve pulpodentin regeneration

Materials Today Bio, Journal Year: 2025, Volume and Issue: 31, P. 101591 - 101591

Published: Feb. 21, 2025

Language: Английский

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Regulation of Skeletogenic Pathways by m6A RNA Modification: A Comprehensive Review

Calcified Tissue International, Journal Year: 2025, Volume and Issue: 116(1)

Published: April 3, 2025

Language: Английский

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Providing biomimetic microenvironment for pulp regeneration via hydrogel-mediated sustained delivery of tissue-specific developmental signals

Materials Today Bio, Journal Year: 2024, Volume and Issue: 26, P. 101102 - 101102

Published: May 27, 2024

Regenerative endodontic therapy is a promising approach to restore the vitality of necrotic teeth, however, pulp regeneration in mature permanent teeth remains substantial challenge due insufficient developmental signals. The dentin embryologically and histologically similar pulp, which contains cocktail pulp-specific structural proteins growth factors, thus we proposed an optimizing strategy obtain matrix extracted (DMEP) engineered DMEP functionalized double network hydrogel, whose physicochemical property was tunable by adjusting polymer concentrations synchronize with regenerated tissues.

Language: Английский

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Regenerative application of oral and maxillofacial 3D organoids based on dental pulp stem cell

Tissue and Cell, Journal Year: 2024, Volume and Issue: 89, P. 102451 - 102451

Published: June 24, 2024

Language: Английский

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Calcium‐sensing receptor regulates the angiogenic differentiation of LPS‐treated human dental pulp cells via the phosphoinositide 3‐kinase/Akt pathway in vitro

International Endodontic Journal, Journal Year: 2024, Volume and Issue: 57(11), P. 1655 - 1668

Published: July 30, 2024

Abstract Aim The purpose of this study was to investigate the role calcium‐sensing receptor (CaSR) in angiogenic differentiation lipopolysaccharide (LPS)‐treated human dental pulp cells (hDPCs). Methodology LPS‐induced hDPCs were cultured medium with different combinations CaSR agonist R568 and antagonist Calhex231. cell proliferation, migration, capacity measured by Cell Counting Kit‐8 (CCK‐8), scratch wound healing, tube formation assays, respectively. Enzyme‐linked immunosorbent assay (ELISA), quantitative real‐time polymerase chain reaction (qRT‐PCR), western blot conducted determine gene/protein expression CaSR, inflammatory mediators, angiogenic‐associated markers. activation phosphoinositide 3‐kinase (PI3K) protein kinase B (Akt) assessed analysis. Results proliferation elevated response or Calhex231 exposure, but an enhanced migration only found cultures supplemented Furthermore, potentiate vessel‐like structure, up‐regulated tumour necrosis factor (TNF)‐α, vascular endothelial growth (VEGF), stromal cell‐derived (SDF)‐1; comparable influences also observed R568‐stimulated presence PI3K inhibitor LY294002. In contrast, obviously inhibited VEGF level, whereas promoted production IL‐6, TNF‐α, eNOS; however, LY294002, showed a significant promotion on VEGF, SDF‐1. addition, exhibited promotive action Akt phosphorylation, which can be reversed Conclusions Our results demonstrated that regulate LPS‐treated involvement PI3K/Akt signalling pathway.

Language: Английский

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Isolation, Cryopreservation, and Differentiation Methods of DPSC

Springer eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 127 - 155

Published: Jan. 1, 2024

Language: Английский

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ADM-Loaded GelMA hydrogel promotes endogenous dental pulp regeneration: an in vitro and in vivo study

Journal of Endodontics, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

To prepare a gelatin methacryloyl (GelMA) hydrogel scaffold embedded with adrenomedullin (ADM) and investigate its impact underlying mechanisms in endogenous pulp regeneration. ADM was evenly distributed within the GelMA through simple conventional physical mixing technique. The underwent characterization via scanning electron microscopy, alongside assessments of swelling, degradation, release properties. Biocompatibility evaluated using cytoskeletal live-dead staining techniques. hydrogel's influence on dental stem cells' proliferation, migration, differentiation assessed CCK-8 assays, Transwell alizarin red alkaline phosphatase staining. Transcriptomics provided insights into potential mechanisms. angiogenic effects umbilical vein endothelial cells were examined scratch tube formation assays. In vivo, composite regenerative capacity tested rat model Statistical analysis involved Student's t-test one-way variance, significance set at P < .05. ADM-loaded (GelMA@ADM) displayed porous architecture under microscopy conducive to cell adhesion demonstrated excellent biocompatibility. vitro experiments showed that GelMA@ADM significantly boosted differentiation, enhanced activity after one week treatment. Corresponding vivo revealed facilitated new vascularized tissue 2 weeks effectively promotes proliferation augments vascularization by cells, fosters creation tissue. These findings underscore for

Language: Английский

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Silencing lncRNA TUG1 inhibits osteo/odontogenic differentiation of human dental pulp stem cells through the Wnt/β-catenin signaling pathway

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 15, 2024

Background Human dental pulp stem cells (hDPSCs), a type of mesenchymal (MSCs), can be induced to various tissues under appropriate conditions. LncRNA TUG1 has been shown exert promoting effect on osteogenic differentiation, while its role in osteo/odontogenic differentiation hDPSCs remains unclear. This study aimed investigate the during hDPSCs. Materials and methods The were characterized identified using flow cytometry assessment their multidirectional capabilities. knockdown was achieved by lentivirus-mediated short hairpin RNA (shRNA) confirmed qRT-PCR. ability evaluated alkaline phosphatase (ALP) staining, alizarin red S (ARS) qRT-PCR, western blot. Lithium chloride (LiCl) used as an agonist Wnt/β-catenin signaling pathway. Results experiments successfully. expression upregulated process Knockdown attenuated potential decreased DSPP, DMP-1, Runx2, OCN OPN. Besides, silencing significantly reduced levels pathway related marker proteins, Wnt3a β-catenin, activation LiCl markedly reversed inhibitory Conclusion Our results imply that might function through promote

Language: Английский

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[Advances in Molecular Regulatory Mechanisms of Jaw Repair and Reconstruction].

PubMed, Journal Year: 2024, Volume and Issue: 55(1), P. 224 - 229

Published: Jan. 20, 2024

Jawbone injuries resulting from trauma, diseases, and surgical resections are commonly seen in clinical practice, necessitating precise effective strategies for repair reconstruction to restore both function aesthetics. The the of jawbone pose a significant challenge field oral maxillofacial surgery, owing unique biomechanical characteristics physiological functions jawbone. natural process following involves stages such as hematoma formation, inflammatory response, ossification, bone remodeling. Bone morphogenetic proteins (BMPs), transforming growth factor beta (TGF-β), vascular endothelial (VEGF), other factors play crucial roles promoting regeneration. Cytokines interleukins tumor necrosis dual regulating response repair. In recent years, progress molecular biology research has been made reconstruction. Tissue engineering technologies, including stem cell therapy, bioactive scaffolds, delivery systems, have found important applications However, intricate regulatory mechanisms involved complex methods not fully understood still require further research. Future directions will be focused on control these processes development more efficient combination therapeutic promote functional This review aims examine latest findings strategies. conclusions drawn this article provide molecular-level understanding highlight potential future

Language: Английский

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