Quercetin protects rat BMSCs from oxidative stress via ferroptosis

PI3K/AKT/mTOR通路 蛋白激酶B 化学 氧化应激 运行x2 活力测定 槲皮素 活性氧 下调和上调 碱性磷酸酶 骨桥蛋白 间充质干细胞 分子生物学 细胞生物学 磷酸化 信号转导 生物 细胞凋亡 内分泌学 生物化学 抗氧化剂 基因
作者
Dongmei Lan,Shengcai Qi,Chao Yao,Xue Li,Haijiang Liu,Dan Wang,Yan Wang
出处
期刊:Journal of Molecular Endocrinology [Bioscientifica]
卷期号:69 (3): 401-413 被引量:21
标识
DOI:10.1530/jme-22-0086
摘要

Quercetin has been shown to have a wide range of beneficial effects, such as anti-inflammation, anti-oxidation and immunomodulation. The study was designed to explore the role and molecular mechanisms of quercetin on the protective effect of bone marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress in vitro. BMSCs were isolated from 4-week-old male Sprague-Dawley rats. Upon H2O2 stimulation in vitro, the effects of quercetin on the proliferation, anti-oxidation and osteogenic differentiation of BMSCs were evaluated by Cell Counting Kit-8, reactive oxygen species analysis, Western blot (WB), real-time PCR (RT-PCR), alkaline phosphatase staining and alizarin red staining. Additionally, ferroptosis-related markers were examined by WB, RT-PCR and Mito-FerroGreen. Finally, PI3K/AKT/mTOR signaling pathway was explored in these processes. We found that quercetin significantly maintained BMSCs viability upon H2O2 stimulation. Quercetin upregulated protein (ALP, OPN and RUNX2) and mRNA (Alp, Opn, Ocn and Runx2) levels of osteogenic markers, downregulated ROS levels and upregulated antioxidative gene expressions (Nrf2, Cat, Sod-1 and Sod-2) compared with the H2O2 group. The ferroptosis in BMSCs was activated after H2O2 stimulation, and the phosphorylation level of PI3K, AKT and mTOR was upregulated in H2O2-stimulated BMSCs. More importantly, quercetin inhibited ferroptosis and the phosphorylation level of PI3K, AKT and mTOR were downregulated after quercetin treatment. We conclude that quercetin maintained the viability and the osteoblastic differentiation of BMSCs upon H2O2 stimulation, potentially via ferroptosis inhibition by PI3K/AKT/mTOR pathway.
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