The investigation of effects, signal pathways, and applications of high glucose on dental pulp stem cells

Background/purpose: Dental pulp stem cells (DPSCs) are among the most widely used dental-derived mesenchymal stem cells (MSCs), and their applications have involved various regions. The glucose metabolism plays a key role in cell function and the current literature presents conflicting evidence rega...

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Main Authors: Shih-Yu Lee, I-Hsun Li, Wei-Cheng Tsai, Ming-Hua Ho, Chung-Hsing Li
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Journal of Dental Sciences
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Online Access:http://www.sciencedirect.com/science/article/pii/S1991790225001114
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author Shih-Yu Lee
I-Hsun Li
Wei-Cheng Tsai
Ming-Hua Ho
Chung-Hsing Li
author_facet Shih-Yu Lee
I-Hsun Li
Wei-Cheng Tsai
Ming-Hua Ho
Chung-Hsing Li
author_sort Shih-Yu Lee
collection DOAJ
description Background/purpose: Dental pulp stem cells (DPSCs) are among the most widely used dental-derived mesenchymal stem cells (MSCs), and their applications have involved various regions. The glucose metabolism plays a key role in cell function and the current literature presents conflicting evidence regarding the influence of glucose on MSCs' properties. This study evaluated the impact of high glucose (HG) on DPSCs. Materials and methods: DPSCs were stimulated with indicated concentrations of glucose. Cell viability was assessed using a cell counting kit, while apoptosis and autophagy were analyzed via western blot. MSCs immunophenotypic properties were determined by flow cytometry. Osteogenic, adipogenic, and neurogenic differentiation potential were evaluated using western blot, Alizarin red staining, oil red-O staining, and morphological analysis. Results: HG exposure led to a significant decrease in cell viability, with increased apoptosis and autophagy, as indicated by increased levels of cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), and an elevated microtubule-associated protein 1 light chain 3 beta (LC3B)-II/LC3B-I ratio. However, the immunophenotypic characteristics of DPSCs remained unchanged. DPSCs also demonstrated enhanced osteogenic, adipogenic, and neurogenic differentiation potential by expressing Alizarin red and oil red-O staining, neural-like cell morphology, and several differentiation-related proteins after HG culture stimulation. Conclusion: The present study demonstrated that while HG slightly impairs DPSC viability, it promotes osteogenic, adipogenic, and neurogenic differentiation. Providing valuable insights into the mechanisms by which HG influences various differentiation pathways in DPSCs and establishes a foundation for potential clinical applications of DPSCs in regenerative medicine for diabetic patients.
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spelling doaj-art-2d108d9acad24f5b9e0a0800328a27d92025-06-26T09:52:23ZengElsevierJournal of Dental Sciences1991-79022025-07-0120317311738The investigation of effects, signal pathways, and applications of high glucose on dental pulp stem cellsShih-Yu Lee0I-Hsun Li1Wei-Cheng Tsai2Ming-Hua Ho3Chung-Hsing Li4Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, TaiwanSchool of Pharmacy, National Defense Medical Center, Taipei, TaiwanGraduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, TaiwanDepartment of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, TaiwanDivision of Orthodontics, Pediatric Dentistry, and Special Needs Dentistry, Department of Dentistry, Tri-Service General Hospital, Taipei, Taiwan; School of Dentistry and Graduate Institute of Dental Science, National Defense Medical Center, Taipei, Taiwan; Corresponding author. School of Dentistry and Graduate Institute of Dental Science, National Defense Medical Center, No. 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City 11490, Taiwan.Background/purpose: Dental pulp stem cells (DPSCs) are among the most widely used dental-derived mesenchymal stem cells (MSCs), and their applications have involved various regions. The glucose metabolism plays a key role in cell function and the current literature presents conflicting evidence regarding the influence of glucose on MSCs' properties. This study evaluated the impact of high glucose (HG) on DPSCs. Materials and methods: DPSCs were stimulated with indicated concentrations of glucose. Cell viability was assessed using a cell counting kit, while apoptosis and autophagy were analyzed via western blot. MSCs immunophenotypic properties were determined by flow cytometry. Osteogenic, adipogenic, and neurogenic differentiation potential were evaluated using western blot, Alizarin red staining, oil red-O staining, and morphological analysis. Results: HG exposure led to a significant decrease in cell viability, with increased apoptosis and autophagy, as indicated by increased levels of cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), and an elevated microtubule-associated protein 1 light chain 3 beta (LC3B)-II/LC3B-I ratio. However, the immunophenotypic characteristics of DPSCs remained unchanged. DPSCs also demonstrated enhanced osteogenic, adipogenic, and neurogenic differentiation potential by expressing Alizarin red and oil red-O staining, neural-like cell morphology, and several differentiation-related proteins after HG culture stimulation. Conclusion: The present study demonstrated that while HG slightly impairs DPSC viability, it promotes osteogenic, adipogenic, and neurogenic differentiation. Providing valuable insights into the mechanisms by which HG influences various differentiation pathways in DPSCs and establishes a foundation for potential clinical applications of DPSCs in regenerative medicine for diabetic patients.http://www.sciencedirect.com/science/article/pii/S1991790225001114Dental pulp stem cells (DPSCs)Mesenchymal stem cells (MSCs)High glucose (HG)Diabetes mellitus (DM)Stem cell therapy
spellingShingle Shih-Yu Lee
I-Hsun Li
Wei-Cheng Tsai
Ming-Hua Ho
Chung-Hsing Li
The investigation of effects, signal pathways, and applications of high glucose on dental pulp stem cells
Journal of Dental Sciences
Dental pulp stem cells (DPSCs)
Mesenchymal stem cells (MSCs)
High glucose (HG)
Diabetes mellitus (DM)
Stem cell therapy
title The investigation of effects, signal pathways, and applications of high glucose on dental pulp stem cells
title_full The investigation of effects, signal pathways, and applications of high glucose on dental pulp stem cells
title_fullStr The investigation of effects, signal pathways, and applications of high glucose on dental pulp stem cells
title_full_unstemmed The investigation of effects, signal pathways, and applications of high glucose on dental pulp stem cells
title_short The investigation of effects, signal pathways, and applications of high glucose on dental pulp stem cells
title_sort investigation of effects signal pathways and applications of high glucose on dental pulp stem cells
topic Dental pulp stem cells (DPSCs)
Mesenchymal stem cells (MSCs)
High glucose (HG)
Diabetes mellitus (DM)
Stem cell therapy
url http://www.sciencedirect.com/science/article/pii/S1991790225001114
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