Mesenchymal Stem Cells Protect Nucleus Pulposus Cells from Compression-Induced Apoptosis by Inhibiting the Mitochondrial Pathway.

Mesenchymal Stem Cells Protect Nucleus Pulposus Cells from Compression-Induced Apoptosis by Inhibiting the Mitochondrial Pathway.
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间充质干细胞通过抑制线粒体途径保护髓核细胞免受压迫诱导的细胞凋亡

DOI:
10.1155/2017/9843120
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发表时间:
2017
影响因子:
4.3
通讯作者:
Shao Z
Shao Z
中科院分区:
医学3区
文献类型:
--
作者:
Chen S;Zhao L;Deng X;Shi D;Wu F;Liang H;Huang D;Shao Z

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目的椎间盘退变(IVDD)的发生与各种应力(包括压力)诱导的髓核细胞(NPC)过度凋亡有关。骨髓间充质干细胞(Mesenchymal stem cells,MSCs)可以促进NPC的再生,延缓IVDD的发生,但其分子机制尚不清楚。本研究旨在评价骨髓间充质干细胞(BMSC)对大鼠受压神经前体细胞的抗凋亡作用,并探讨线粒体途径是否参与其中。方法将骨髓间充质干细胞与神经前体细胞在1.0MPa压力下共培养36 h。评价细胞活力、凋亡、线粒体功能和凋亡相关蛋白的表达。结果与骨髓基质细胞共培养可提高NPCs的细胞活力,减少NPCs的凋亡。同时,BMSCs可通过降低活性氧水平、维持线粒体膜电位和线粒体完整性,减轻压力诱导的NPCs线粒体损伤。与BMSCs共培养后,细胞内细胞色素c和Bax的表达降低,Bcl-2的表达增加,caspase-3和caspase-9的活性降低。结论BMSCs可通过抑制线粒体信号通路,对压力诱导的NPCs凋亡起到保护作用,从而加深了我们对以MSCs为基础治疗IVDD的认识。
Objective Excessive apoptosis of nucleus pulposus cells (NPCs) induced by various stresses, including compression, contributes to the development of intervertebral disc degeneration (IVDD). Mesenchymal stem cells (MSCs) can benefit the regeneration of NPCs and delay IVDD, but the underlying molecular mechanism is poorly understood. This study aimed to evaluate the antiapoptosis effects of bone marrow-derived MSC (BMSC) on rat NPCs exposed to compression and investigate whether the mitochondrial pathway was involved. Methods BMSCs and NPCs were cocultured in the compression apparatus at 1.0 MPa for 36 h. Cell viability, apoptosis, mitochondrial function, and the expression of apoptosis-related proteins were evaluated. Results The results showed that coculturing with BMSCs increased the cell viability and reduced apoptosis of NPCs exposed to compression. Meanwhile, BMSCs could relieve the compression-induced mitochondrial damage of NPCs by decreasing reactive oxygen species level and maintaining mitochondrial membrane potential as well as mitochondrial integrity. Furthermore, coculturing with BMSCs suppressed the activated caspase-3 and activated caspase-9, decreased the expressions of cytosolic cytochrome c and Bax, and increased the expression of Bcl-2. Conclusions Our results suggest that BMSCs can protect against compression-induced apoptosis of NPCs by inhibiting the mitochondrial pathway and thus enhance our understanding on the MSC-based therapy for IVDD.
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