Hrubi Edit, Imre László, Hegedüs Csaba
Department of Biomaterials and Prosthetic Dentistry, Faculty of Dentistry, University of Debrecen, Debrecen, H-4032 Hungary.
Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary.
Heliyon. 2024 Jun 8;10(12):e32553. doi: 10.1016/j.heliyon.2024.e32553. eCollection 2024 Jun 30.
Epigenetic mechanisms play regulatory roles in dental pulp stem cell (DPSC) differentiation. The molecules that modulate these mechanisms can be used to enhance DPSC differentiation in experimental studies and clinical applications. We investigated the combined effects of an epigenetic modulator enhancer of zeste homologue 2 inhibitor (EZH2i), trichostatin A (TSA), and 5-azacytidine (5-AZA) on the osteogenic differentiation of DPSCs.
To assess osteogenic differentiation, we measured alkaline phosphatase activity, calcium deposition, and expression of osteogenic differentiation marker genes (, , and ) after 7 or 21 days of combinatorial drug treatment in normal cell culture medium or osteo-inductive medium (OIM). No synergistic effects were observed for any possible combination of EZH2i, TSA, or 5-AZA. However, the effects of these drugs and their combinations depend on the time and culture conditions.
We confirmed that EZH2i and TSA have positive effects on the osteogenic differentiation of DPSCs. EZH2i activates the expression of key regulatory genes (, , and ) directly, whereas TSA interacts with signalling pathways induced by supplements in OIM to activate these genes.
表观遗传机制在牙髓干细胞（DPSC）分化中起调节作用。调节这些机制的分子可用于在实验研究和临床应用中增强DPSC分化。我们研究了表观遗传调节剂zeste同源物2抑制剂（EZH2i）、曲古抑菌素A（TSA）和5-氮杂胞苷（5-AZA）对DPSCs成骨分化的联合作用。
为评估成骨分化，我们在正常细胞培养基或骨诱导培养基（OIM）中进行联合药物处理7天或21天后，测量了碱性磷酸酶活性、钙沉积和成骨分化标记基因（、和）的表达。对于EZH2i、TSA或5-AZA的任何可能组合，均未观察到协同作用。然而，这些药物及其组合的效果取决于时间和培养条件。
我们证实EZH2i和TSA对DPSCs的成骨分化具有积极作用。EZH2i直接激活关键调控基因（、和）的表达，而TSA与OIM中补充剂诱导的信号通路相互作用以激活这些基因。
