The role of reactive oxygen species in mesenchymal stem cell adipogenic and osteogenic differentiation: a review.

The role of reactive oxygen species in mesenchymal stem cell adipogenic and osteogenic differentiation: a review.
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DOI:
10.1089/scd.2014.0484
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发表时间:
2015-05-15
影响因子:
4
通讯作者:
Pepper MS
Pepper MS
中科院分区:
医学3区
文献类型:
--
作者:
Atashi F;Modarressi A;Pepper MS

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间充质基质细胞(MSCs)是组织工程和再生医学的理想候选细胞。MSC分离物的多能干细胞组分能够分化成中胚层谱系的衍生物,包括脂肪细胞、骨细胞、软骨细胞和肌细胞。许多共同的途径已被描述在调节脂肪和骨生成。然而,刺激成骨似乎抑制脂肪形成,反之亦然。越来越多的证据表明活性氧(ROS)对这些过程的严格调节。ROS是短寿命的含氧分子,对DNA、RNA、蛋白质和脂质显示出高化学反应性。线粒体复合物I和III以及NADPH氧化酶亚型NOX 4是MSC分化过程中ROS产生的主要来源。ROS被认为与影响MSC分化所需的转录机制的几种途径相互作用,包括Wnt、Hedgehog和FOXO信号级联。另一方面,ROS水平升高(定义为氧化应激)导致MSC细胞周期停滞和细胞凋亡。因此,严格调节的ROS水平对于MSC终末分化至关重要,尽管涉及的ROS的精确来源、定位、水平和确切种类仍有待确定。本文综述了活性氧对骨髓间充质干细胞成脂和成骨分化的影响。
Mesenchymal stromal cells (MSCs) are promising candidates for tissue engineering and regenerative medicine. The multipotent stem cell component of MSC isolates is able to differentiate into derivatives of the mesodermal lineage including adipocytes, osteocytes, chondrocytes, and myocytes. Many common pathways have been described in the regulation of adipogenesis and osteogenesis. However, stimulation of osteogenesis appears to suppress adipogenesis and vice-versa. Increasing evidence implicates a tight regulation of these processes by reactive oxygen species (ROS). ROS are short-lived oxygen-containing molecules that display high chemical reactivity toward DNA, RNA, proteins, and lipids. Mitochondrial complexes I and III, and the NADPH oxidase isoform NOX4 are major sources of ROS production during MSC differentiation. ROS are thought to interact with several pathways that affect the transcription machinery required for MSC differentiation including the Wnt, Hedgehog, and FOXO signaling cascades. On the other hand, elevated levels of ROS, defined as oxidative stress, lead to arrest of the MSC cell cycle and apoptosis. Tightly regulated levels of ROS are therefore critical for MSC terminal differentiation, although the precise sources, localization, levels and the exact species of ROS implicated remain to be determined. This review provides a detailed overview of the influence of ROS on adipogenic and osteogenic differentiation in MSCs.
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