Pioglitazone Protects Compression-Mediated Apoptosis in Nucleus Pulposus Mesenchymal Stem Cells by Suppressing Oxidative Stress
Pioglitazone Protects Compression-Mediated Apoptosis in Nucleus Pulposus Mesenchymal Stem Cells by Suppressing Oxidative Stress
复制标题
吡格列酮通过抑制氧化应激来保护髓核间充质干细胞中压缩介导的细胞凋亡
DOI：
10.1155/2019/4764071
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发表时间：
2019-11-22
影响因子：
--
通讯作者：
Xiong, Liming
中科院分区：
文献类型：
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作者：
Hu, Yiqiang;Huang, Liang;Xiong, Liming
过度压迫是椎间盘退变的主要原因，影响椎间盘的内源性修复。吡格列酮（PGZ）是过氧化物酶体增殖物激活受体γ激动剂，已广泛用于糖尿病的治疗。本研究旨在探讨吡格列酮对压力介导的髓核间充质干细胞（NP-MSCs）凋亡的保护作用及其可能的机制。结果表明，所分离的细胞符合国际细胞治疗学会（International Society for Cellular Therapy）提出的MSC标准。此外，吡格列酮可保护NP-MSCs的细胞活力、细胞增殖，减轻压迫引起的毒性作用。肌动蛋白应力纤维在压力下明显受到抑制，吡格列酮可减轻不良后果。Annexin V/PI双染和TUNEL法显示吡格列酮对压力诱导的NP-MSCs凋亡具有保护作用。吡格列酮抑制压迫诱导的NP-MSCs氧化应激，包括减少压迫诱导的活性氧（ROS）和丙二醛（MDA）的过度产生，并减轻压迫诱导的线粒体膜电位（MMP）降低。透射电子显微镜（TEM）显示，在压缩诱导的NP-MSCs中，吡格列酮可显著改善线粒体的超微结构塌陷。此外，分子生物学结果显示，吡格列酮显著降低了凋亡相关蛋白的表达，包括细胞色素c、Bax、裂解的caspase-9和裂解的caspase-3，并促进Bcl-2的表达。这些结果表明，吡格列酮通过抑制氧化应激和线粒体凋亡途径减轻压迫诱导的NP-MSCs凋亡，这可能是治疗IVD变性的一个有价值的候选药物。
Excessive compression, the main cause of intervertebral disc (IVD) degeneration, affected endogenous repair of the intervertebral disc. Pioglitazone (PGZ) is the agonist of peroxisome proliferator-activated receptor gamma, which has been widely used in the treatment of diabetes mellitus. The present study aim at investigating whether pioglitazone has protective effects on compression-mediated cell apoptosis in nucleus pulposus mesenchymal stem cells (NP-MSCs) and further exploring the possible underlying mechanism. Our results indicated that the isolated cells satisfied the criteria of MSC stated by the International Society for Cellular Therapy. Besides, our research revealed that pioglitazone could protect cell viability, cell proliferation of NP-MSCs and alleviated the toxic effects caused by compression. The actin stress fibers was suppressed obviously under compression, and pioglitazone alleviated the adverse outcomes. Pioglitazone exerted protective effects on compression-induced NP-MSCs apoptosis according to annexin V/PI double-staining and TUNEL assays. Pioglitazone suppressed compression-induced NP-MSCs oxidative stress, including decreasing compression-induced overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA), and alleviated compression-induced mitochondrial membrane potential (MMP) decrease. Ultrastructure collapse of the mitochondria exhibited a notable improvement by pioglitazone in compression-induced NP-MSCs according to transmission electron microscopy (TEM). Furthermore, the molecular results showed that pioglitazone significantly decreased the expression of apoptosis-associated proteins, including cyto.cytochrome c, Bax, cleaved caspase-9, and cleaved caspase-3, and promoted Bcl-2 expression. These results indicated that pioglitazone alleviated compression-induced NP-MSCs apoptosis by suppressing oxidative stress and the mitochondrial apoptosis pathway, which may be a valuable candidate for the treatment of IVD degeneration.