Mesenchymal stem cell-derived exosome mediated long non-coding RNA KLF3-AS1 represses autophagy and apoptosis of chondrocytes in osteoarthritis
Mesenchymal stem cell-derived exosome mediated long non-coding RNA KLF3-AS1 represses autophagy and apoptosis of chondrocytes in osteoarthritis
复制标题
间充质干细胞来源的外泌体介导的长非编码RNA KLF3-AS1抑制骨关节炎中软骨细胞的自噬和凋亡
DOI：
10.1080/15384101.2021.2019411
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发表时间：
2021-12-24
期刊：
影响因子：
4.3
通讯作者：
Liu, Yubao
中科院分区：
文献类型：
--
作者：
Wen, Chuanyang;Lin, Lupan;Liu, Yubao
骨关节炎是一种退行性关节疾病，是导致成人残疾的主要原因。我们先前的研究报告了间充质干细胞衍生的外泌体（MSC-Exo）介导的长非编码RNA KLF 3-AS 1改善骨关节炎。本研究旨在探讨KLF 3-AS 1在骨关节炎发病中的分子机制。用IL-1 β处理软骨细胞以诱导软骨细胞损伤，然后进行MSC-Exo处理。我们发现MSC-Exo增强了IL-1 β处理的软骨细胞中KLF 3-AS 1的表达。IL-1 β处理降低了软骨细胞的细胞活力并增强了软骨细胞的凋亡。MSC-Exo介导的KLF 3-AS 1促进细胞活力并抑制IL-1 β处理的软骨细胞的凋亡。雷帕霉素（自噬激活剂）通过激活自噬促进细胞活力并抑制软骨细胞凋亡。此外，KLF 3-AS 1与YBX 1在软骨细胞中相互作用。MSC-Exo介导的KLF 3-AS 1激活PI 3 K/Akt/mTOR信号通路，该通路被YBX 1沉默所废除。MSC-Exo介导的KLF 3-AS 1通过激活PI 3 K/Akt/mTOR信号通路抑制软骨细胞自噬和凋亡。结论：MSC-Exo介导的KLF 3-AS 1通过PI 3 K/Akt/mTOR信号通路抑制IL-1 β诱导的软骨细胞自噬和凋亡。KLF 3-AS 1通过靶向YBX 1激活PI 3 K/Akt/mTOR信号通路，改善骨关节炎的进展。因此，这项工作表明MSC-Exo介导的KLF 3-AS 1可能是骨关节炎的潜在治疗靶点。
Osteoarthritis is a degenerative joint disease and a leading cause of adult disability. Our previous study has reported that mesenchymal stem cell-derived exosomes (MSC-Exo) mediated long non-coding RNA KLF3-AS1 improves osteoarthritis. This study aims to investigate the molecular mechanism of KLF3-AS1 in osteoarthritis. Chondrocytes were treated with IL-1 beta to induce chondrocyte injury, followed by MSC-Exo treatment. We found that MSC-Exo enhanced KLF3-AS1 expression in IL-1 beta-treated chondrocytes. IL-1 beta treatment reduced cell viability and enhanced apoptosis in chondrocytes. MSC-Exo-mediated KLF3-AS1 promoted cell viability and repressed apoptosis of IL-1 beta-treated chondrocytes. Rapamycin (autophagy activator) promoted cell viability and suppressed apoptosis of chondrocytes by activating autophagy. Moreover, KLF3-AS1 interacted with YBX1 in chondrocytes. MSC-Exo-mediated KLF3-AS1 activated PI3K/Akt/mTOR signaling pathway, which was abrogated by YBX1 silencing. MSC-Exo-mediated KLF3-AS1 repressed autophagy and apoptosis of chondrocytes by activating PI3K/Akt/mTOR signaling pathway. In conclusion, our data demonstrate that MSC-Exo-mediated KLF3-AS1 inhibits autophagy and apoptosis of IL-1 beta-treated chondrocyte through PI3K/Akt/mTOR signaling pathway. KLF3-AS1 activates PI3K/Akt/mTOR signaling pathway by targeting YBX1 to improve the progression of osteoarthritis. Thus, this work suggests that MSC-Exo-mediated KLF3-AS1 may be a potential therapeutic target for osteoarthritis.