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Exosomes derived from mesenchymal stem cells inhibit mitochondrial dysfunction-induced apoptosis of chondrocytes via p38, ERK, and Akt pathways

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Abstract

Osteoarthritis (OA) is the most common chronic joint disease worldwide. Chondrocyte, as the only resident cell type in cartilage, its apoptosis is of pathogenetic significance in OA. Mesenchymal stem cell (MSC)-based-therapy has been proved effective in OA in animals and clinical studies. Nowadays, the regenerative potential of MSC-based therapy is mostly attributed to its paracrine secretion, in which exosomes may play an important role. In the present study, we aimed to find out the significance of MSC-derived exosomes (MSC-Exos) on the viability of chondrocytes under normal and inflammatory conditions. Bone marrow MSCs (BMSCs) and chondrocytes from rabbits were cultured in vitro. BMSC-Exos were isolated by an ultracentrifugation method. Transmission electron microscopy and Western blot were used to identify exosomes. The internalization of BMSC-Exos into chondrocytes was observed by fluorescent microscope. The viability and apoptosis of chondrocytes induced by IL-1β were tested through MTT method, Hoechst33324 dying, and mitochondrial damage measurement. Phosphorylation of p38, ERK, and Akt were evaluated by Western blot. The results showed that BMSC-Exos were round-shaped. Co-culturing BMSC-Exos with chondrocytes could observe the uptake of BMSC-Exos by chondrocytes. The viability decreased, apoptosis occurred, and the mitochondrial membrane potential of chondrocytes changed a lot when IL-1β were given, but all the changes were almost abolished when BMSC-Exos was added. Furthermore, the phosphorylation of p38 and ERK were inhibited, and phosphorylation of Akt was promoted by BMSC-Exos compared with IL-1β group. The present study demonstrated that BMSC-Exos inhibited mitochondrial-induced apoptosis in response to IL-1β, and p38, ERK, and Akt pathways were involved. BMSC-Exo might represent a novel cell-free therapeutic approach for the treatment of OA.

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Authors and Affiliations

  1. Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing, 100035, China

    Hui Qi & Shao-Feng Jin

  2. Department of Orthopaedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, China

    Dan-Ping Liu, Da-Wei Xiao, Da-Chuan Tian & Yong-Wei Su

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  1. Hui Qi
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  2. Dan-Ping Liu
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Correspondence to Hui Qi.

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Qi, H., Liu, DP., Xiao, DW. et al. Exosomes derived from mesenchymal stem cells inhibit mitochondrial dysfunction-induced apoptosis of chondrocytes via p38, ERK, and Akt pathways. In Vitro Cell.Dev.Biol.-Animal 55, 203–210 (2019). https://doi.org/10.1007/s11626-019-00330-x

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