Alcohol Induces Cellular Senescence and Impairs Osteogenic Potential in Bone Marrow-Derived Mesenchymal Stem Cells
Alcohol Induces Cellular Senescence and Impairs Osteogenic Potential in Bone Marrow-Derived Mesenchymal Stem Cells
复制标题
酒精会诱导细胞衰老并损害骨髓间充质干细胞的成骨潜力。
DOI：
10.1093/alcalc/agx006
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发表时间：
2017-05-01
影响因子：
2.8
通讯作者：
He, Fan
中科院分区：
文献类型：
--
作者：
Chen, Xi;Li, Mao;He, Fan
目的：长期和过量饮酒是骨质疏松症的高危因素。骨髓间充质干细胞（BM-MSCs）在骨形成中起重要作用；然而，它们对乙醇（EtOH）很脆弱。本研究的目的是探讨EtOH是否会诱导BM-MSCs过早衰老，并随后损害其成骨潜能。方法：将人BM-MSCs暴露于10 ~ 250 mM的EtOH中，观察衰老相关的β -半乳糖苷酶（sa - β -gal）活性、细胞周期分布、细胞增殖和活性氧（ROS）。在etoh处理的BM-MSCs成骨过程中评估矿化和成骨细胞特异性基因表达。为了研究沉默信息调节因子1型（SIRT1）在etoh诱导的衰老中的作用，我们使用白藜芦醇（ResV）激活etoh处理的脑-间充质干细胞中的SIRT1。结果：EtOH处理导致BM-MSCs出现衰老相关表型，如细胞增殖减少、sa - β -gal活性增加和G0/G1细胞周期阻滞。EtOH还增加了细胞内ROS和衰老相关基因p16（INK4 α）和p21的表达。在etoh处理的BM-MSCs中，SIRT1水平的下调伴随着成骨分化的抑制被证实。ResV激活SIRT1部分抵消了EtOH的作用，减少了衰老标志物，恢复了被抑制的成骨。结论：EtOH治疗以剂量依赖的方式诱导BM-MSCs过早衰老，这是EtOH损伤成骨分化的原因。SIRT1的激活可有效改善etoh诱导的骨髓间充质干细胞衰老表型，并可能为临床预防或治疗酒精性骨质疏松症提供一种新的策略。摘要：乙醇（EtOH）治疗以剂量依赖的方式诱导骨髓间充质干细胞过早衰老，这是EtOH损伤成骨分化的原因。SIRT1的激活可有效改善乙醇诱导的衰老表型，这可能为临床治疗酒精诱导的骨质疏松症提供一种新的策略。
Aims: Chronic and excessive alcohol consumption is a high-risk factor for osteoporosis. Bone marrow-derived mesenchymal stem cells (BM-MSCs) play an important role in bone formation; however, they are vulnerable to ethanol (EtOH). The purpose of this research was to investigate whether EtOH could induce premature senescence in BM-MSCs and subsequently impair their osteogenic potential.Methods: Human BM-MSCs were exposed to EtOH ranging from 10 to 250 mM. Senescence-associated beta-galactosidase (SA-beta-gal) activity, cell cycle distribution, cell proliferation and reactive oxygen species (ROS) were evaluated. Mineralization and osteoblast-specific gene expression were evaluated during osteogenesis in EtOH-treated BM-MSCs. To investigate the role of silent information regulator Type 1 (SIRT1) in EtOH-induced senescence, resveratrol (ResV) was used to activate SIRT1 in EtOH-treated BM-MSCs.Results: EtOH treatments resulted in senescence-associated phenotypes in BM-MSCs, such as decreased cell proliferation, increased SA-beta-gal activity and G0/G1 cell cycle arrest. EtOH also increased the intracellular ROS and the expression of senescence-related genes, such as p16(INK4 alpha) and p21. The down-regulated levels of SIRT1 accompanied with suppressed osteogenic differentiation were confirmed in EtOH-treated BM-MSCs. Activation of SIRT1 by ResV partially counteracted the effects of EtOH by decreasing senescence markers and rescuing the inhibited osteogenesis.Conclusion: EtOH treatments induced premature senescence in BM-MSCs in a dose-dependent manner that was responsible for EtOH-impaired osteogenic differentiation. Activation of SIRT1 was effective in ameliorating EtOH-induced senescence phenotypes in BMSCs and could potentially lead to a new strategy for clinically preventing or treating alcohol-induced osteoporosis.Short summary: Ethanol (EtOH) treatments induce premature senescence in marrow-derived mesenchymal stem cells in a dose-dependent manner that is responsible for EtOH-impaired osteogenic differentiation. Activation of SIRT1 is effective in ameliorating EtOH-induced senescence phenotypes, which potentially leads to a new strategy for clinically treating alcohol-induced osteoporosis.