Histone H3 Lysine 9 Acetylation Plays a Role in Adipogenesis of Periodontal Ligament-Derived Stem Cells

Background: The epigenetic regulation of adipogenic differentiation in dental stem cells (DSCs) remains poorly understood, as research has prioritized osteogenic differentiation for dental applications. However, elucidating these mechanisms could enable novel regenerative strategies for soft tissue...

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Main Authors: Julio A. Montero-Del-Toro, Angelica A. Serralta-Interian, Geovanny I. Nic-Can, Mónica Lamas, Rodrigo A. Rivera-Solís, Beatriz A. Rodas-Junco
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Epigenomes
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Online Access:https://www.mdpi.com/2075-4655/9/2/15
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author Julio A. Montero-Del-Toro
Angelica A. Serralta-Interian
Geovanny I. Nic-Can
Mónica Lamas
Rodrigo A. Rivera-Solís
Beatriz A. Rodas-Junco
author_facet Julio A. Montero-Del-Toro
Angelica A. Serralta-Interian
Geovanny I. Nic-Can
Mónica Lamas
Rodrigo A. Rivera-Solís
Beatriz A. Rodas-Junco
author_sort Julio A. Montero-Del-Toro
collection DOAJ
description Background: The epigenetic regulation of adipogenic differentiation in dental stem cells (DSCs) remains poorly understood, as research has prioritized osteogenic differentiation for dental applications. However, elucidating these mechanisms could enable novel regenerative strategies for soft tissue engineering. Periodontal ligament stem cells (PDLSCs) exhibit notable adipogenic potential, possibly linked to histone 3 acetylation at lysine 9 (H3K9ac); however, the mechanistic role of this modification remains unclear. Methods: To address this gap, we investigated how histone deacetylase inhibitors (HDACis)—valproic acid (VPA, 8 mM) and trichostatin A (TSA, 100 nM)—modulate H3K9ac dynamics, adipogenic gene expression (<i>C/EBPβ</i> and <i>PPARγ-2</i>), and chromatin remodeling during PDLSCs differentiation. Techniques used included quantitative PCR (qPCR), lipid droplet analysis, and chromatin immunoprecipitation followed by qPCR (ChIP-qPCR). Results: TSA-treated cells exhibited increased lipid deposition with smaller lipid droplets compared to VPA-treated cells. Global H3K9ac levels correlated positively with adipogenic progression. VPA induced early upregulation of <i>C/EBPβ</i> and <i>PPARγ-2</i> (day 7), whereas TSA triggered a delayed but stronger <i>PPARγ-2</i> expression. ChIP-qPCR analysis revealed significant H3K9ac enrichment at the <i>PPARγ-2</i> promoter in TSA-treated cells, indicating enhanced chromatin accessibility. Conclusions: These findings demonstrate that H3K9ac-mediated epigenetic remodeling plays a critical role in the adipogenic differentiation of PDLSCs and identifies TSA as a potential tool for modulating this process.
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spelling doaj-art-490c1c852cf044f09c2b042ca04f60712025-08-20T02:21:09ZengMDPI AGEpigenomes2075-46552025-05-01921510.3390/epigenomes9020015Histone H3 Lysine 9 Acetylation Plays a Role in Adipogenesis of Periodontal Ligament-Derived Stem CellsJulio A. Montero-Del-Toro0Angelica A. Serralta-Interian1Geovanny I. Nic-Can2Mónica Lamas3Rodrigo A. Rivera-Solís4Beatriz A. Rodas-Junco5Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Mérida 97203, MexicoFacultad de Ingeniería Química, Universidad Autónoma de Yucatán, Mérida 97203, MexicoSECIHTI-Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Mérida 97203, MexicoDepartamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados-Sede Sur, Ciudad de México 07360, MexicoFacultad de Ingeniería Química, Universidad Autónoma de Yucatán, Mérida 97203, MexicoLaboratorio de Células Troncales, Facultad de Odontología, Universidad Autónoma de Yucatán, Mérida 97000, MexicoBackground: The epigenetic regulation of adipogenic differentiation in dental stem cells (DSCs) remains poorly understood, as research has prioritized osteogenic differentiation for dental applications. However, elucidating these mechanisms could enable novel regenerative strategies for soft tissue engineering. Periodontal ligament stem cells (PDLSCs) exhibit notable adipogenic potential, possibly linked to histone 3 acetylation at lysine 9 (H3K9ac); however, the mechanistic role of this modification remains unclear. Methods: To address this gap, we investigated how histone deacetylase inhibitors (HDACis)—valproic acid (VPA, 8 mM) and trichostatin A (TSA, 100 nM)—modulate H3K9ac dynamics, adipogenic gene expression (<i>C/EBPβ</i> and <i>PPARγ-2</i>), and chromatin remodeling during PDLSCs differentiation. Techniques used included quantitative PCR (qPCR), lipid droplet analysis, and chromatin immunoprecipitation followed by qPCR (ChIP-qPCR). Results: TSA-treated cells exhibited increased lipid deposition with smaller lipid droplets compared to VPA-treated cells. Global H3K9ac levels correlated positively with adipogenic progression. VPA induced early upregulation of <i>C/EBPβ</i> and <i>PPARγ-2</i> (day 7), whereas TSA triggered a delayed but stronger <i>PPARγ-2</i> expression. ChIP-qPCR analysis revealed significant H3K9ac enrichment at the <i>PPARγ-2</i> promoter in TSA-treated cells, indicating enhanced chromatin accessibility. Conclusions: These findings demonstrate that H3K9ac-mediated epigenetic remodeling plays a critical role in the adipogenic differentiation of PDLSCs and identifies TSA as a potential tool for modulating this process.https://www.mdpi.com/2075-4655/9/2/15dental stem cellshistone deacetylase inhibitorsadipogenic differentiationperiodontal ligament stem cellshistone H3 lysine 9 acetylation
spellingShingle Julio A. Montero-Del-Toro
Angelica A. Serralta-Interian
Geovanny I. Nic-Can
Mónica Lamas
Rodrigo A. Rivera-Solís
Beatriz A. Rodas-Junco
Histone H3 Lysine 9 Acetylation Plays a Role in Adipogenesis of Periodontal Ligament-Derived Stem Cells
Epigenomes
dental stem cells
histone deacetylase inhibitors
adipogenic differentiation
periodontal ligament stem cells
histone H3 lysine 9 acetylation
title Histone H3 Lysine 9 Acetylation Plays a Role in Adipogenesis of Periodontal Ligament-Derived Stem Cells
title_full Histone H3 Lysine 9 Acetylation Plays a Role in Adipogenesis of Periodontal Ligament-Derived Stem Cells
title_fullStr Histone H3 Lysine 9 Acetylation Plays a Role in Adipogenesis of Periodontal Ligament-Derived Stem Cells
title_full_unstemmed Histone H3 Lysine 9 Acetylation Plays a Role in Adipogenesis of Periodontal Ligament-Derived Stem Cells
title_short Histone H3 Lysine 9 Acetylation Plays a Role in Adipogenesis of Periodontal Ligament-Derived Stem Cells
title_sort histone h3 lysine 9 acetylation plays a role in adipogenesis of periodontal ligament derived stem cells
topic dental stem cells
histone deacetylase inhibitors
adipogenic differentiation
periodontal ligament stem cells
histone H3 lysine 9 acetylation
url https://www.mdpi.com/2075-4655/9/2/15
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