MSC-Derived Exosomes Protect Vertebral Endplate Chondrocytes against Apoptosis and Calcification via the miR-31-5p/ATF6 Axis

Lin Xie; Zhenhao Chen; Ming Liu; Weibo Huang; Fei Zou; Xiaosheng Ma; Jie Tao; Jingkang Guo; Xinlei Xia; Feizhou Lyu; Hongli Wang; Chaojun Zheng; Jianyuan Jiang

Molecular Therapy: Nucleic Acids (Dec 2020)

MSC-Derived Exosomes Protect Vertebral Endplate Chondrocytes against Apoptosis and Calcification via the miR-31-5p/ATF6 Axis

Lin Xie,
Zhenhao Chen,
Ming Liu,
Weibo Huang,
Fei Zou,
Xiaosheng Ma,
Jie Tao,
Jingkang Guo,
Xinlei Xia,
Feizhou Lyu,
Hongli Wang,
Chaojun Zheng,
Jianyuan Jiang

Affiliations

Lin Xie: Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai 200040, China
Zhenhao Chen: Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai 200040, China
Ming Liu: Department of Orthopedic Surgery, Wuhan Fourth Hospital, Huazhong University of Science and Technology, Wuhan 430000, China
Weibo Huang: Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai 200040, China
Fei Zou: Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai 200040, China
Xiaosheng Ma: Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai 200040, China
Jie Tao: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200436, China
Jingkang Guo: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200436, China
Xinlei Xia: Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai 200040, China
Feizhou Lyu: Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai 200040, China; Department of Orthopedic Surgery, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai 201100, China
Hongli Wang: Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai 200040, China; Corresponding author: Hongli Wang, Department of Orthopedics, Huashan Hospital, Fudan University, 12 Mid-Wulumuqi Road, Shanghai 200040, China.
Chaojun Zheng: Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai 200040, China; Corresponding author: Chaojun Zheng, Department of Orthopedics, Huashan Hospital, Fudan University, 12 Mid-Wulumuqi Road, Shanghai 200040, China.
Jianyuan Jiang: Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai 200040, China; Corresponding author: Jianyuan Jiang, Department of Orthopedics, Huashan Hospital, Fudan University, 12 Mid-Wulumuqi Road, Shanghai 200040, China.

Journal volume & issue: Vol. 22
pp. 601 – 614

Abstract

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Apoptosis and calcification of endplate chondrocytes (EPCs) can exacerbate intervertebral disc degeneration (IVDD). Mesenchymal stem cell-derived exosomes (MSC-exosomes) are reported to have the therapeutic potential in IVDD. However, the effects and related mechanisms of MSC-exosomes on EPCs are still unclear. We aimed to investigate the role of MSC-exosomes on EPCs with a tert-butyl hydroperoxide (TBHP)-induced oxidative stress cell model and IVDD rat model. First, our study revealed that TBHP could result in apoptosis and calcification of EPCs, and MSC-exosomes could inhibit the detrimental effects. We also found that these protective effects were inhibited after miroRNA (miR)-31-5p levels were downregulated in MSC-exosomes. The target relationship between miR-31-5p and ATF6 was tested. miR-31-5p negatively regulated ATF6-related endoplasmic reticulum (ER) stress and inhibited apoptosis and calcification in EPCs. Our in vivo experiments indicated that sub-endplate injection of MSC-exosomes can ameliorate IVDD; however, after miR-31-5p levels were downregulated in MSC-exosomes, these protective effects were inhibited. In conclusion, MSC-exosomes reduced apoptosis and calcification in EPCs, and the underlying mechanism may be related to miR-31-5p/ATF6/ER stress pathway regulation.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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