Extracellular vesicles derived from LPS-preconditioned human synovial mesenchymal stem cells inhibit extracellular matrix degradation and prevent osteoarthritis of the knee in a mouse model

来自 LPS 预处理的人类滑膜间充质干细胞的细胞外囊泡可抑制细胞外基质降解并预防小鼠模型中的膝关节骨关节炎

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作者:Ao Duan #, Kai Shen #, Beichen Li #, Cong Li #, Hao Zhou, Renyi Kong, Yuqi Shao, Jian Qin, Tangbo Yuan, Juan Ji, Wei Guo, Xipeng Wang, Tengfei Xue, Lei Li, Xinxin Huang, Yuqin Sun, Zhenyu Cai, Wei Liu, Feng Liu

Background

Previous studies report that lipopolysaccharide (LPS)-preconditioned mesenchymal stem cells have enhanced trophic support and improved regenerative and repair properties. Extracellular vesicles secreted by synovial mesenchymal stem cells (EVs) can reduce cartilage damage caused by osteoarthritis (OA). Previous studies show that extracellular vesicles secreted by LPS-preconditioned synovial mesenchymal stem cells (LPS-pre EVs) can improve the response to treatment of osteoarthritis (OA). This study sought to explore effects of LPS-pre EVs on chondrocyte proliferation, migration, and chondrocyte apoptosis, as well as the protective effect of LPS-pre EVs on mouse articular cartilage.

Conclusions

LPS pretreatment is an effective and promising method to improve therapeutic effect of extracellular vesicles secreted from SMSCs on OA.

Methods

Chondrocytes were extracted to explore the effect of LPS-pre EVs on proliferation, migration, and apoptosis of chondrocytes. In addition, the effect of LPS-pre EVs on expression level of important proteins of chondrocytes was explored suing in vitro experiments. Further, intraarticular injection of LPS-pre EVs was performed on the destabilization of the medial meniscus (DMM)-induced mouse models of OA to explore the therapeutic effect of LPS-pre EVs on osteoarthritis in vivo.

Results

Analysis showed that LPS-pre EVs significantly promoted proliferation and migration of chondrocytes and inhibited the apoptosis of chondrocytes compared with PBS and EVs. Moreover, LPS-pre EVs inhibited decrease of aggrecan and COL2A1 and increase of ADAMTS5 caused by IL-1β through let-7b. Furthermore, LPS-pre EVs significantly prevented development of OA in DMM-induced mouse models of OA. Conclusions: LPS pretreatment is an effective and promising method to improve therapeutic effect of extracellular vesicles secreted from SMSCs on OA.

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