Apoptotic BMSCs-Derived Extracellular Vesicles Promote Bone Repair Via Activating the ROS-Induced JNK Signal

44 Pages Posted: 12 May 2021

See all articles by Maojiao Li

Maojiao Li

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases

Xiaotao Xing

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases

Haisen Huang

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases

Cheng Liang

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases

Xin Gao

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases

Qi Tang

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases

Xun Xu

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases

Jian Yang

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases

Li Liao

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases

Weidong Tian

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases

Abstract

The transplantation of bone marrow mesenchymal stem cells (BMSCs) promotes bone repair and regeneration. However, it has been shown that the majority of BMSCs die within a short period after transplantation. During apoptosis, BMSCs generate a large number of apoptotic cell-derived extracellular vesicles (ApoEVs). This study aims to understand the potential role of ApoEVs in bone defect repair and regeneration. We confirm that BMSCs undergo apoptosis 2 days after transplantation into the defect of the cranium. In vitro, we find that abundant ApoEVs were generated by apoptotic BMSCs and can be engulfed by BMSCs and promote the proliferation, migration, and osteogenic differentiation of recipient cells. ApoEVs from cells in the middle stage of apoptosis were the most efficient at enhancing the regeneration capacity of BMSCs. In vivo, transplantation of ApoEVs in the calvarial defect region significantly promoted bone regeneration in both mouse and rat models. Mechanistically, ApoEVs promote new bone formation by upregulating the Reactive Oxygen Species (ROS) and activating the JNK signaling. This study reveals a previously unknown role of the dying transplanted BMSCs in promoting the viability of endogenous BMSCs and repairing the bone defects. Since it could avoid several adverse effects and limits of BMSCs cytotherapy, treatment of ApoEVs might be a promising strategy in bone repair and regeneration.

Suggested Citation

Li, Maojiao and Xing, Xiaotao and Huang, Haisen and Liang, Cheng and Gao, Xin and Tang, Qi and Xu, Xun and Yang, Jian and Liao, Li and Tian, Weidong, Apoptotic BMSCs-Derived Extracellular Vesicles Promote Bone Repair Via Activating the ROS-Induced JNK Signal. Available at SSRN: https://ssrn.com/abstract=3844704 or http://dx.doi.org/10.2139/ssrn.3844704

Maojiao Li

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases ( email )

Chengdu
China

Xiaotao Xing

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases ( email )

Chengdu
China

Haisen Huang

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases ( email )

Chengdu
China

Cheng Liang

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases ( email )

Chengdu
China

Xin Gao

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases

Chengdu
China

Qi Tang

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases

Chengdu
China

Xun Xu

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases

Chengdu
China

Jian Yang

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases

Chengdu
China

Li Liao (Contact Author)

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases ( email )

Chengdu
China

Weidong Tian

Sichuan University - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases ( email )

Chengdu
China

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