The role and underlying mechanism of dental pulp stem cell-derived exosomal miR-31 in the treatment of osteoarthritis by targeting mTOR to enhance chondrocyte autophagy levels

牙髓干细胞来源的外泌体miR-31通过靶向mTOR增强软骨细胞自噬水平在骨关节炎治疗中的作用及机制

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作者:Guanglei Zhao, Jinyang Lyu, Xin Huang, Gangyong Huang, Feiyan Chen, Yibing Wei, Siqun Wang, Jun Xia, Jie Chen, Jingsheng Shi

Conclusions

Furthermore, DPSC-exosomes show an ability to promote autophagy in chondrocytes through mTOR inhibition, in addition to reducing the mTOR luciferase activity. The ability of DPSC-exosomes to partially regulate autophagy was blocked upon inhibition of miR-31. In brief, DPSC-exosomes have a chondroprotective role in a mouse osteoarthritis model. The underlying mechanism is possibly related to miR-31-mediated suppression of the mTOR-autophagy pathway.

Material and methods

In this in vitro and in vivo study, we studied the effects and mechanisms of dental pulp stem cell-derived exosomes (DPSC-exosomes) on osteoarthritis in a mouse model.

Methods

In this in vitro and in vivo study, we studied the effects and mechanisms of dental pulp stem cell-derived exosomes (DPSC-exosomes) on osteoarthritis in a mouse model.

Results

The study findings showed that a dental pulp stem cell could generate typical characteristic exosomes. The injection of DPSC-exosomes ameliorated destruction of cartilage, promoted matrix synthesis, inhibited cell apoptosis, and decreased the expression of catabolic factors. However, this effect was shown to be almost eliminated when miR-31 antagomir was injected. Conclusions: Furthermore, DPSC-exosomes show an ability to promote autophagy in chondrocytes through mTOR inhibition, in addition to reducing the mTOR luciferase activity. The ability of DPSC-exosomes to partially regulate autophagy was blocked upon inhibition of miR-31. In brief, DPSC-exosomes have a chondroprotective role in a mouse osteoarthritis model. The underlying mechanism is possibly related to miR-31-mediated suppression of the mTOR-autophagy pathway.

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