Autophagy protects bone marrow mesenchymal stem cells from palmitate‑induced apoptosis through the ROS‑JNK/p38 MAPK signaling pathways

Liu,Yongyi; Wang,Ning; Zhang,Shaokun; Liang,Qingwei

doi:10.3892/mmr.2018.9100

Autophagy protects bone marrow mesenchymal stem cells from palmitate‑induced apoptosis through the ROS‑JNK/p38 MAPK signaling pathways

Authors:
- Yongyi Liu
- Ning Wang
- Shaokun Zhang
- Qingwei Liang
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Affiliations: Department of Orthopedics, The First Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China, Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Sports Medicine, The First Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China
Published online on: May 30, 2018 https://doi.org/10.3892/mmr.2018.9100
Pages: 1485-1494
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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Abstract

In recent years, the association between saturated fatty acids (FA) and bone cells has received a high level of attention. Previous studies have shown that palmitate (PA), a common saturated FA, can cause apoptosis in bone marrow mesenchymal stem cells (BMSCs). However, whether PA can induce autophagy, an important intracellular protection mechanism that is closely associated with apoptosis, in BMSCs is still unknown; the association between autophagy and apoptosis is also unclear. The aim of the present study was to determine whether PA can induce autophagy in BMSCs. When BMSCs were treated with PA for >18 h, p62 began to accumulate, indicating that autophagic flux was impaired by prolonged exposure to PA. In addition, the proportion of apoptotic cells was increased when autophagy was inhibited by the autophagy inhibitor 3‑methyladenine. Furthermore, inducing autophagy by pretreating cells with rapamycin, a known inducer of autophagy, markedly reduced PA‑induced apoptosis, suggesting that autophagy may serve a protective role in PA‑induced apoptosis in BMSCs. PA also increased intracellular reactive oxygen species (ROS) production, which was decreased by the antioxidant N‑Acetyl‑cysteine, and promoted the activation of c‑Jun N‑terminal kinases (JNKs) and p38 mitogen‑activated protein kinase (MAPK). The addition of JNK and p38 MAPK inhibitors substantially reduced autophagy. Therefore, the results indicated that PA can induce autophagy in BMSCs and protect cells from PA‑induced apoptosis through the ROS‑JNK/p38 MAPK signaling pathways. These results may improve the general understanding of the mechanisms through which BMSCs adapt to PA‑induced apoptosis. The present study also provides a novel approach for the prevention and treatment of PA‑induced lipotoxicity.

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