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ArticleCurrent stem cell research & therapy2025

Histone Deacetylase Inhibitors Restore the Odontogenic Differentiation Potential of Dental Pulp Stem Cells under Hyperglycemic Conditions.

Mahshid Hodjat, Fatemeh Farshad, Mahdi Gholami, Mohammad Abdollahi, Khandakar Asm Saadat

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Article in Current stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1 citing paper in PubMed.

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5 · Who and what money

Authors and funding

5 authors.

Mahshid HodjatDental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences (TUMS), Tehran, Iran.ORCID 0000-0001-8335-3546
Fatemeh FarshadDental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Mahdi GholamiDepartment of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Mohammad AbdollahiDepartment of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Khandakar Asm SaadatDepartment of Medical Biology and Genetics, Faculty of Medicine, Graduate Institute of Health Sciences, Gaziantep University, Gaziantep 27310, Turkey.

Funding

NIMAD, National Institute for Medical Research Development 983142Tehran University of Medical Sciences 98-02-70-42379
6 · The paper itself

Abstract

objectiveComplications arising from diabetes can result in stem cell dysfunction, impairing their ability to undergo differentiation into various cellular lineages. The present study evaluated the effect of histone deacetylase inhibitors, Valproic acid and Trichostatin A, on the odontogenic differentiation potential of dental pulp stem cells under hyperglycemic conditions.

methodsStreptozotocin (STZ) induced diabetes mellitus in 12 male Wistar rats. Dental parameters were examined using micro-computed tomography. The odontogenic potential of human pulp stem cells exposed to 30 mM glucose was assessed through alkaline phosphatase assays, examination of gene expression for dentin matrix protein 1 and dentin sialoprotein using real-time PCR, and alizarin red staining for calcium deposition.

resultsAlong with reduced dentin thickness and root length in diabetic rats, the results revealed a significant increase in histone deacetylase 3 and 2 gene expressions in isolated diabetic pulp tissues compared to the control groups. The gene expression of odontogenic-related markers and alkaline phosphatase activity in human cultured pulp stem cells under hyperglycemic conditions significantly decreased. Adding Valproic acid and Trichostatin A restored the odontogenic differentiation markers, including calcium deposition, gene expression of dentin sialophosphoprotein, dentin matrix protein 1, and alkaline phosphatase activity.

conclusionThe data suggests that hyperglycemic conditions negatively impact the odontogenic potential of pulp mesenchymal stem cells. However, histone deacetylase inhibitors improve the impaired odontogenic differentiation capacity. This study implies that histone deacetylases may represent a potential therapeutic target for enhancing the regenerative mineralization of pulp cells in diabetic patients.

Indexed as

Cell DifferentiationDental PulpDiabetes Mellitus, ExperimentalHistone Deacetylase InhibitorsHyperglycemiaOdontogenesisStem CellsAnimalsCells, CulturedDentin SialophosphoproteinExtracellular Matrix ProteinsHumansHydroxamic AcidsMalePhosphoproteinsRatsDentin SialophosphoproteinExtracellular Matrix ProteinsHistone Deacetylase InhibitorsHydroxamic AcidsPhosphoproteinsSialoglycoproteinstrichostatin AValproic Acidchronic hyperglycemiadentin.Diabetes mellitushistone deacetylase inhibitorsmesenchymal stem cellsodontogenic differentiation

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.