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

IF 2.5 Q3 GENETICS & HEREDITY

Epigenomes Pub Date : 2025-05-24 DOI:10.3390/epigenomes9020015

Julio A Montero-Del-Toro, Angelica A Serralta-Interian, Geovanny I Nic-Can, Mónica Lamas, Rodrigo A Rivera-Solís, Beatriz A Rodas-Junco

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引用次数: 0

Abstract

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 (C/EBPβ and PPARγ-2), 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 C/EBPβ and PPARγ-2 (day 7), whereas TSA triggered a delayed but stronger PPARγ-2 expression. ChIP-qPCR analysis revealed significant H3K9ac enrichment at the PPARγ-2 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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组蛋白H3赖氨酸9乙酰化在牙周韧带干细胞脂肪形成中的作用

背景：牙干细胞（DSCs）成脂分化的表观遗传调控仍然知之甚少，因为研究优先考虑牙科应用的成骨分化。然而，阐明这些机制可以为软组织工程提供新的再生策略。牙周韧带干细胞（PDLSCs）表现出显著的成脂潜能，可能与组蛋白3赖氨酸9乙酰化（H3K9ac）有关；然而，这种修饰的机制作用仍不清楚。方法：为了弥补这一空白，我们研究了组蛋白去乙酰化酶抑制剂(hdac)-丙戊酸（VPA, 8 mM）和曲古霉素A （TSA, 100 nM）在PDLSCs分化过程中如何调节H3K9ac动力学、脂肪生成基因表达（C/EBPβ和PPARγ-2）和染色质重塑。使用的技术包括定量PCR （qPCR）、脂滴分析和染色质免疫沉淀，然后进行qPCR （ChIP-qPCR）。结果：与vpa处理的细胞相比，tsa处理的细胞表现出更小的脂滴和更多的脂质沉积。全球H3K9ac水平与脂肪生成进展呈正相关。VPA诱导了C/EBPβ和PPARγ-2的早期上调（第7天），而TSA触发了延迟但更强的PPARγ-2表达。ChIP-qPCR分析显示，在tsa处理的细胞中，PPARγ-2启动子上的H3K9ac显著富集，表明染色质可及性增强。结论：这些发现表明h3k9ac介导的表观遗传重塑在PDLSCs的成脂分化中起着关键作用，并确定TSA是调节这一过程的潜在工具。

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