Mesenchymal stem cell-derived exosome mediated long non-coding RNA KLF3-AS1 represses autophagy and apoptosis of chondrocytes in osteoarthritis

• Published in: Cell cycle (Georgetown, Tex.) Vol. ahead-of-print; no. ahead-of-print; pp. 1 - 15
• Main Authors: Wen, Chuanyang, Lin, Lupan, Zou, Rui, Lin, Fuqing, Liu, Yubao
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.02.2022
• Subjects: apoptosis; Apoptosis - genetics; autophagy; Autophagy - genetics; Chondrocytes - metabolism; exosome; Exosomes - metabolism; Humans; KLF3-AS1; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Mesenchymal stem cell; Mesenchymal Stem Cells - metabolism; Osteoarthritis - genetics; Osteoarthritis - metabolism; Phosphatidylinositol 3-Kinases - metabolism; PI3K/Akt/mTOR; Proto-Oncogene Proteins c-akt - metabolism; Research Paper; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; TOR Serine-Threonine Kinases - metabolism; YBX1; Mesenchymal stem cell; OA; autophagy; KLF3-AS1; apoptosis; YBX1; PI3K/Akt/mTOR; exosome
• ISSN: 1538-4101; 1551-4005
• DOI: 10.1080/15384101.2021.2019411

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-1β to induce chondrocyte injury, followed by MSC-Exo treatment. We found that MSC-Exo enhanced KLF3-AS1 expression in IL-1β-treated chondrocytes. IL-1β treatment reduced cell viability and enhanced apoptosis in chondrocytes. MSC-Exo-mediated KLF3-AS1 promoted cell viability and repressed apoptosis of IL-1β-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-1β-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.