This study aimed to explore the effect of KAT6A on the decreased stemness of aging bone marrow-derived mesenchymal stem cells (BMSCs) and its potential mechanism. The acetylation level and KAT6A expression of BMSCs from the young (YBMSCs) and the old (OBMSCs) were examined. Gain- and loss-of-function experiments were performed to determine the effect of KAT6A on BMSC proliferation, colony formation, and osteogenic differentiation. The effect of KAT6A on Nrf2/ARE signaling pathway was investigated after KAT6A inhibition in YBMSCs or overexpression in OBMSCs, and the role of Nrf2/ARE signaling pathway on stemness was examined by investigating proliferation, colony formation, and osteogenic differentiation. Further in vivo study was performed to explore osteogenesis ability of OBMSCs after modulation of KAT6A and Nrf2/ARE pathway through cell sheet technology. The acetylation level and KAT6A expression of OBMSCs were decreased, and KAT6A downregulation resulted in decreased proliferation, colony formation, and osteogenic differentiation of OBMSCs. Mechanically, KAT6A was found to regulate Nrf2/ARE signaling pathway and inhibit ROS accumulation in OBMSCs, thus promoting proliferation, colony formation, and osteogenic differentiation of OBMSCs. Further study demonstrated that KAT6A could promote osteogenesis of OBMSCs by regulating Nrf2/ARE signaling pathway. Downregulation of KAT6A resulted in the decreased stemness of OBMSCs by inhibiting the Nrf2/ARE signaling pathway. KAT6A was downregulated in aging bone marrow-derived mesenchymal stem cells (BMSCs), and downregulation of KAT6A resulted in Nrf2/ARE signaling pathway inhibition and ROS accumulation, thus leading to decreased stemness of aging BMSCs.

中文翻译：

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KAT6A通过Nrf2/ARE信号通路调控衰老骨髓间充质干细胞的干性

本研究旨在探讨KAT6A对衰老骨髓间充质干细胞（BMSCs）干性降低的影响及其潜在机制。检查来自年轻（YBMSCs）和老年（OBMSCs）的BMSCs的乙酰化水平和KAT6A表达。进行功能增益和功能丧失实验以确定 KAT6A 对 BMSC 增殖、集落形成和成骨分化的影响。在 YBMSCs 中抑制 KAT6A 或在 OBMSCs 中过表达后，研究了 KAT6A 对 Nrf2/ARE 信号通路的影响，并通过研究增殖、集落形成和成骨分化来检查 Nrf2/ARE 信号通路对干性的作用。进一步进行体内研究以探索通过细胞片技术调节 KAT6A 和 Nrf2/ARE 通路后 OBMSCs 的成骨能力。OBMSCs的乙酰化水平和KAT6A表达降低，KAT6A下调导致OBMSCs增殖、集落形成和成骨分化减少。机械地，发现KAT6A调节Nrf2 / ARE信号通路并抑制OBMSCs中的ROS积累，从而促进OBMSCs的增殖、集落形成和成骨分化。进一步研究表明，KAT6A 可通过调节 Nrf2/ARE 信号通路促进 OBMSCs 成骨。KAT6A 的下调通过抑制 Nrf2/ARE 信号通路导致 OBMSCs 的干性降低。