Quercetin protects rat BMSCs from oxidative stress via ferroptosis

Author:

Lan Dongmei123ORCID,Qi Shengcai123,Yao Chao123,Li Xue123,Liu Haijiang24,Wang Dan567,Wang Yan28

Affiliation:

1. Department of Prosthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, China

2. Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, China

3. Medical College, Anhui University of Science and Technology, Huainan, China

4. Department of Endodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, China

5. Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China

6. School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR, China

7. Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong SAR, China

8. Department of Preventive Dentistry, Shanghai Stomatological Hospital, Fudan University, Shanghai, China

Abstract

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.

Publisher

Bioscientifica

Subject

Endocrinology,Molecular Biology

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