Cartilage endplate stem cells inhibit intervertebral disc degeneration by releasing exosomes to nucleus pulposus cells to activate Akt/autophagy.
Cartilage endplate stem cells inhibit intervertebral disc degeneration by releasing exosomes to nucleus pulposus cells to activate Akt/autophagy.
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DOI：
10.1002/stem.3322
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Luo L;Jian X;Sun H;Qin J;Wang Y;Zhang J;Shen Z;Yang D;Li C;Zhao P;Liu M;Tian Z;Zhou Y
软骨终板（CEP）的退变可导致椎间盘退变（IVDD）。髓核细胞（Nucleus pulposus cell，NPC）凋亡也是IVDD的重要加重因素，但其级联机制尚不清楚。我们在体外和体内研究了正常软骨终板干细胞（CESC）来源的外泌体（N-Exos）和变性CESC来源的外泌体（D-Exos）刺激时NPC和IVDD的凋亡。使用叔丁基过氧化氢（TBHP）诱导CESC的炎症。使用质谱、热图和京都基因和基因组百科全书（KEGG）富集分析来分析N-Exos和D-Exos之间的生物信息学差异。TUNEL法检测鼻咽癌细胞凋亡。使用信号传导抑制剂LY 294002研究了AKT和自噬信号传导途径的参与。使用磁共振成像、蛋白质印迹和免疫荧光染色来评价N-Exos在患有IVDD的大鼠中的治疗效果。TBHP可明显诱导大鼠CEP的炎症和变性。N-Exos比D-Exos更有利于自噬激活。与D-Exos相比，N-Exos处理后NPC的凋亡率明显降低。N-Exos通过激活AKT和自噬途径抑制大鼠NPC凋亡并减弱IVDD。这些结果是证实CEP通过外泌体延迟IVDD进展的第一个发现。由于PI 3 K/AKT/自噬通路的激活，N-Exos对NPC细胞凋亡抑制和减缓IVDD进展的治疗效果比D-Exos更有效，这解释了CEP炎症后IVDD发生率的增加。软骨终板（CEP）炎症加速椎间盘退变（IVDD）进展的机制图解摘要。正常软骨终板干细胞（CESC）来源的外泌体（N-Exos）比变性CEPC来源的外泌体（D-Exos）更有效地抑制髓核细胞（NPC）凋亡，因为CEP变性后外泌体携带的抗凋亡蛋白减少。此外，N-Exos比D-Exos更有效地激活NPC中的PI 3 K/AKT信号通路，增强自噬，减轻NPC的体外凋亡，改善体内IVDD
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. 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
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影响因子：
25.7
作者：
Nojima H;Freeman CM;Schuster RM;Japtok L;Kleuser B;Edwards MJ;Gulbins E;Lentsch AB
通讯作者：
Lentsch AB
影响因子：
4.7
作者：
Li, Fang-Cai;Zhang, Ning;Chen, Qi-Xin
通讯作者：
Chen, Qi-Xin
影响因子：
1.6
作者：
Liang L;Li X;Li D;Jiang W;Wang H;Chen J;Sun Z;Zhang N;Zhu Y
通讯作者：
Zhu Y
DOI：
10.1002/stem.3322
发表时间：
2021-04
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Luo L;Jian X;Sun H;Qin J;Wang Y;Zhang J;Shen Z;Yang D;Li C;Zhao P;Liu M;Tian Z;Zhou Y
通讯作者：
Zhou Y
人脐带间充质干细胞来源的外泌体通过激活PI3K/Akt/mTOR通路对H9C2细胞发挥抗凋亡作用
影响因子：
4
作者：
Liu, Hui;Sun, Xiaolu;Wang, Guogan
通讯作者：
Wang, Guogan