Degenerative Nucleus Pulposus Cells Derived Exosomes Promoted Cartilage Endplate Cells Apoptosis and Aggravated Intervertebral Disc Degeneration.
Degenerative Nucleus Pulposus Cells Derived Exosomes Promoted Cartilage Endplate Cells Apoptosis and Aggravated Intervertebral Disc Degeneration.
复制标题
退变髓核细胞来源的Exosomes促进软骨终板细胞凋亡并加重椎间盘退变。
DOI：
10.3389/fmolb.2022.835976
复制
发表时间：
2022
影响因子：
5
通讯作者：
Tan J
中科院分区：
文献类型：
--
作者：
Feng X;Li Y;Su Q;Tan J
椎间盘退变是一种复杂的多因素疾病模型，其发病机制尚未完全明确。关于髓核细胞（NP）与软骨终板细胞（CEP）之间信息相互作用的研究很少。外泌体作为细胞间信息交流的载体，已成为近年来的研究热点。本研究的目的是探讨退行性NP细胞来源的外泌体是否促进CEP细胞凋亡和加重IVD变性。TNFα诱导变性NP细胞模型。从NP细胞培养基上清液中分离出NPC外泌体。CCK-8法检测NP细胞和CEP细胞的活力。外泌体经TEM、NTA和western blot鉴定。细胞免疫荧光和qRT-PCR检测细胞外基质（ECM）代谢。流式细胞术和TUNEL检测细胞凋亡。采用x线及磁共振成像（MRI）、苏木精-伊红（H&E）、橘红O-Green染色评价IVD变性程度。TNFα对NPC活力影响较小，但抑制ECM合成并促进ECM降解。TNFα-NPC-Exo对CEPC增殖影响较小，但促进CEPC凋亡，影响ECM代谢，抑制聚集蛋白和胶原II表达，增强MMP-3表达。TNFα-NPC-Exo加重大鼠IVD变性，促进CEPC凋亡。综上所述，本研究表明退化的npc -外泌体可诱导CEPCs凋亡，抑制ECM合成，促进ECM降解。此外，还证明了npc -外泌体的退化加重了IVD的变性。
Intervertebral disc (IVD) degeneration is a complex multifactorial disease model, which pathogenesis has not been fully defined. There are few studies on the information interaction between nucleus pulposus (NP) cells and cartilage endplate (CEP) cells. Exosomes, as a carrier of information communication between cells, have become a research hotspot recently. The purpose of this study was to explore whether degenerative NP cells-derived exosomes promoted CEP cells apoptosis and aggravated IVD degeneration. The degenerative NP cells model was induced by TNFα. NPC exosomes were isolated from the supernatant of the NP cell culture medium. The viability of NP cells and CEP cells was examined by CCK-8 assays. The exosomes were identified by TEM, NTA, and western blot. Extracellular matrix (ECM) metabolism was measured by cellular immunofluorescence and qRT-PCR. Apoptosis was detected by flow cytometry and TUNEL. X-ray and magnetic resonance imaging (MRI), as well as hematoxylin-eosin (H&E), Safranine O-Green staining was adopted to evaluate IVD degeneration grades. TNFα had a minor impact on NPC viability but inhibited ECM synthesis and promoted ECM degradation. TNFα-NPC-Exo had less effect on CEPC proliferation but promoted CEPC apoptosis and affect ECM metabolism, inhibiting aggrecan and collagen II expression and enhancing MMP-3 expression. TNFα-NPC-Exo aggravates IVD degeneration in a rat model and promoted CEPC apoptosis. In conclusion, this study demonstrated that degenerated NPC-exosome could induce apoptosis of CEPCs, inhibit ECM synthesis, and promote ECM degradation. In addition, it was proved that degenerated NPC-exosome aggravates IVD degeneration.
登录
查看更多内容
DOI：
10.1016/j.bbadis.2014.10.008
发表时间：
2015-01
影响因子：
6.2
作者：
Ailawadi, Shaina;Wang, Xiaohong;Gu, Haitao;Fan, Guo-Chang
通讯作者：
Fan, Guo-Chang
影响因子：
5.2
作者：
Khan AN;Jacobsen HE;Khan J;Filippi CG;Levine M;Lehman RA Jr;Riew KD;Lenke LG;Chahine NO
通讯作者：
Chahine NO
影响因子：
3
作者：
Masuda, K;Aota, Y;An, HS
通讯作者：
An, HS
影响因子：
12.4
作者：
Li P;Kaslan M;Lee SH;Yao J;Gao Z
通讯作者：
Gao Z
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