Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR Pathway
Osteoporosis bears an imbalance between bone formation and resorption, which is strongly related to oxidative stress. The function of leonurine on bone marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress is still unclear. Therefore, this study was aimed at identifying the protective...
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MDPI AG
2022-05-01
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author | Bingkun Zhao Qian Peng Dan Wang Rong Zhou Raorao Wang Yizhun Zhu Shengcai Qi |
author_facet | Bingkun Zhao Qian Peng Dan Wang Rong Zhou Raorao Wang Yizhun Zhu Shengcai Qi |
author_sort | Bingkun Zhao |
collection | DOAJ |
description | Osteoporosis bears an imbalance between bone formation and resorption, which is strongly related to oxidative stress. The function of leonurine on bone marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress is still unclear. Therefore, this study was aimed at identifying the protective effect of leonurine on H<sub>2</sub>O<sub>2</sub> stimulated rat BMSCs. We found that leonurine can alleviate cell apoptosis and promote the differentiation ability of rat BMSCs induced by oxidative stress at an appropriate concentration at 10 μM. Meanwhile, the intracellular ROS level and the level of the COX2 and NOX4 mRNA decreased after leonurine treatment in vitro. The ATP level and mitochondrial membrane potential were upregulated after leonurine treatment. The protein level of PINK1 and Parkin showed the same trend. The mitophage in rat BMSCs blocked by 3-MA was partially rescued by leonurine. Bioinformatics analysis and leonurine-protein coupling provides a strong direct combination between leonurine and the PI3K protein at the position of Asp841, Glu880, Val882. In conclusion, leonurine protects the proliferation and differentiation of BMSCs from oxidative stress by activating mitophagy, which depends on the PI3K/Akt/mTOR pathway. The results showed that leonurine may have potential usage in osteoporosis and bone defect repair in osteoporosis patients. |
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language | English |
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spelling | doaj.art-978669d1da7a4b4b9e5ddba6f6ed84b22023-11-23T13:51:46ZengMDPI AGCells2073-44092022-05-011111172410.3390/cells11111724Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR PathwayBingkun Zhao0Qian Peng1Dan Wang2Rong Zhou3Raorao Wang4Yizhun Zhu5Shengcai Qi6Department of Stomatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Stomatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaInstitute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Stomatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Stomatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaState Key Laboratory of Quality Research in Chinese Medicine, School of Pharmacy, Macau University of Science and Technology, Macau SAR 999078, ChinaDepartment of Stomatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaOsteoporosis bears an imbalance between bone formation and resorption, which is strongly related to oxidative stress. The function of leonurine on bone marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress is still unclear. Therefore, this study was aimed at identifying the protective effect of leonurine on H<sub>2</sub>O<sub>2</sub> stimulated rat BMSCs. We found that leonurine can alleviate cell apoptosis and promote the differentiation ability of rat BMSCs induced by oxidative stress at an appropriate concentration at 10 μM. Meanwhile, the intracellular ROS level and the level of the COX2 and NOX4 mRNA decreased after leonurine treatment in vitro. The ATP level and mitochondrial membrane potential were upregulated after leonurine treatment. The protein level of PINK1 and Parkin showed the same trend. The mitophage in rat BMSCs blocked by 3-MA was partially rescued by leonurine. Bioinformatics analysis and leonurine-protein coupling provides a strong direct combination between leonurine and the PI3K protein at the position of Asp841, Glu880, Val882. In conclusion, leonurine protects the proliferation and differentiation of BMSCs from oxidative stress by activating mitophagy, which depends on the PI3K/Akt/mTOR pathway. The results showed that leonurine may have potential usage in osteoporosis and bone defect repair in osteoporosis patients.https://www.mdpi.com/2073-4409/11/11/1724osteoporosisleonurinemitophagy |
spellingShingle | Bingkun Zhao Qian Peng Dan Wang Rong Zhou Raorao Wang Yizhun Zhu Shengcai Qi Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR Pathway Cells osteoporosis leonurine mitophagy |
title | Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR Pathway |
title_full | Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR Pathway |
title_fullStr | Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR Pathway |
title_full_unstemmed | Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR Pathway |
title_short | Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR Pathway |
title_sort | leonurine protects bone mesenchymal stem cells from oxidative stress by activating mitophagy through pi3k akt mtor pathway |
topic | osteoporosis leonurine mitophagy |
url | https://www.mdpi.com/2073-4409/11/11/1724 |
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