Cartilage endplate stem cells inhibit intervertebral disc degeneration by releasing exosomes to nucleus pulposus cells to activate Akt/autophagy. (18th January 2021)

• Record Type: Journal Article
• Authors: Luo, Liwen; Jian, Xiuying; Sun, Hui; Qin, Jinghao; Wang, Yanqiu; Zhang, Ji; Shen, Zigang; Yang, Di; Li, Changqing; Zhao, Ping; Liu, MingHan; Tian, Zhiqiang; Zhou, Yue
• Is Part Of: Stem cells. Volume 39:Number 4(2021)
• Page Start: 467
• Page End: 481
• Publication Date: 2021-01-18
• Subjects: apoptosis -- autophagy -- cartilage endplate stem cells -- exosome -- intervertebral disc degeneration; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.3322
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: Degeneration of the cartilage endplate (CEP) induces intervertebral disc degeneration (IVDD). Nucleus pulposus cell (NPC) apoptosis is also an important exacerbating factor in IVDD, but the cascade mechanism in IVDD is not clear. We investigated the apoptosis of NPCs and IVDD when stimulated by normal cartilage endplate stem cell (CESC)‐derived exosomes (N‐Exos) and degenerated CESC‐derived exosomes (D‐Exos) in vitro and in vivo. Tert‐butyl hydroperoxide (TBHP) was used to induce inflammation of CESCs. The bioinformatics differences between N‐Exos and D‐Exos were analyzed using mass spectrometry, heat map, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. NPC apoptosis was examined using TUNEL staining. The involvement of the AKT and autophagy signaling pathways was investigated using the signaling inhibitor LY294002. Magnetic resonance imaging, Western blotting, and immunofluorescence staining were used to evaluate the therapeutic effects of N‐Exos in rats with IVDD. TBHP effectively induced inflammation and the degeneration of CEP in rat. N‐Exos were more conducive to autophagy activation than D‐Exos. The apoptotic rate of NPCs decreased obviously after treatment with N‐Exos compared to D‐Exos. N‐Exos inhibited NPCs apoptosis and attenuated IVDD in rat via activation of the AKT and autophagy pathways. These results are the first findings to confirm that CEP delayed the progression of IVDD via exosomes. The therapeutic effects of N‐Exos on NPC apoptosis inhibition and the slowing of IVDD progression were more effective than D‐Exos due to activation of the PI3K/AKT/autophagy pathway, which explained the increase in the incidence of IVDD after inflammation of the CEP. Abstract : Graphical abstract of the mechanism that cartilage endplate (CEP) inflammation accelerated the progression of intervertebral disc degeneration (IVDD). Normal cartilage endplate stem cell (CESC)‐derived exosomes (N‐Exos) can more effectively inhibit nucleus pulposus cell (NPC) apoptosis than degenerated CEPC‐derived exosomes (D‐Exos) due to the anti‐apoptotic protein carried by exosomes decreasing after the CEP degeneration. Furthermore, N‐Exos also activate the PI3K/AKT signaling pathway in NPC more conducively compared with D‐Exos, enhancing autophagy, alleviating NPC apoptosis in vitro and ameliorating IVDD in vivo