间充质干细胞
微泡
内质网
未折叠蛋白反应
细胞凋亡
细胞生物学
程序性细胞死亡
蛋白激酶B
癌症研究
椎间盘
干细胞
信号转导
病理
医学
生物
解剖
小RNA
基因
生物化学
作者
Zhiwei Liao,Rongjin Luo,Gaocai Li,Yu Song,Shengfeng Zhan,Kangcheng Zhao,Wenbin Hua,Yukun Zhang,Xinghuo Wu,Cao Yang
出处
期刊:Theranostics
[Ivyspring International Publisher]
日期:2019-01-01
卷期号:9 (14): 4084-4100
被引量:257
摘要
Objectives: Intervertebral disc degeneration (IDD) is widely accepted as a cause of low back pain and related degenerative musculoskeletal disorders. Nucleus pulposus (NP) cell apoptosis which is related to excessive endoplasmic reticulum (ER) stress in the intervertebral disc (IVD) could aggravate IDD progression. Many studies have shown the therapeutic potential of exosomes derived from bone marrow mesenchymal stem cells (MSC-exos) in degenerative diseases. We hypothesized that the delivery of MSC-exos could modulate ER stress and inhibit excessive NP cell apoptosis during IDD. Methods: The ER stress levels were measured in normal or degenerative NP tissues for contrast. The effects of MSC-exos were testified in advanced glycation end products (AGEs) -induced ER stress in human NP cells. The mechanism involving AKT and ERK signaling pathways was investigated using RNA interference or signaling inhibitors. Histological or immunohistochemical analysis and TUNEL staining were used for evaluating MSC-exos therapeutic effects in vivo. Results: The ER stress level and apoptotic rate was elevated in degenerative IVD tissues. MSC-exos could attenuate ER stress-induced apoptosis by activating AKT and ERK signaling. Moreover, delivery of MSC-exos in vivo modulated ER stress-related apoptosis and retarded IDD progression in a rat tail model. Conclusions: These results highlight the therapeutic effects of exosomes in preventing IDD progression. Our work is the first to demonstrate that MSC-exos could modulate ER stress-induced apoptosis during AGEs-associated IVD degeneration.
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