Chen Sheng, Zhao Lei, Deng Xiangyu, Shi Deyao, Wu Fashuai, Liang Hang, Huang Donghua, Shao Zengwu
Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Stem Cells Int. 2017;2017:9843120. doi: 10.1155/2017/9843120. Epub 2017 Dec 14.
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.
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.
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 and Bax, and increased the expression of Bcl-2.
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.
包括压缩在内的各种应激诱导的髓核细胞(NPCs)过度凋亡,促进了椎间盘退变(IVDD)的发展。间充质干细胞(MSCs)可促进NPCs的再生并延缓IVDD,但其潜在的分子机制尚不清楚。本研究旨在评估骨髓源性MSC(BMSC)对受压大鼠NPCs的抗凋亡作用,并探讨线粒体途径是否参与其中。
将BMSCs和NPCs在压缩装置中于1.0 MPa共培养36小时。评估细胞活力、凋亡、线粒体功能及凋亡相关蛋白的表达。
结果显示,与BMSCs共培养可提高受压NPCs的细胞活力并减少其凋亡。同时,BMSCs可通过降低活性氧水平、维持线粒体膜电位及线粒体完整性来减轻NPCs的压缩诱导的线粒体损伤。此外,与BMSCs共培养可抑制活化的caspase-3和活化的caspase-9,降低胞质细胞色素和Bax的表达,并增加Bcl-2的表达。
我们的结果表明,BMSCs可通过抑制线粒体途径来保护NPCs免受压缩诱导的凋亡,从而增进我们对基于MSC的IVDD治疗的理解。