Chen Xi, Li Mao, Yan Jinku, Liu Tao, Pan Guoqing, Yang Huilin, Pei Ming, He Fan
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou 215153, Jiangsu, China.
Orthopaedic Institute, Medical College, Soochow University, No. 708 Renmin Road, Suzhou 215007, China.
Alcohol Alcohol. 2017 May 1;52(3):289-297. doi: 10.1093/alcalc/agx006.
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.
Human BM-MSCs were exposed to EtOH ranging from 10 to 250 mM. Senescence-associated β-galactosidase (SA-β-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.
EtOH treatments resulted in senescence-associated phenotypes in BM-MSCs, such as decreased cell proliferation, increased SA-β-gal activity and G0/G1 cell cycle arrest. EtOH also increased the intracellular ROS and the expression of senescence-related genes, such as p16INK4α 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.
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.
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.
长期过量饮酒是骨质疏松的高危因素。骨髓间充质干细胞（BM-MSCs）在骨形成中起重要作用；然而，它们易受乙醇（EtOH）影响。本研究的目的是探讨EtOH是否能诱导BM-MSCs过早衰老，进而损害其成骨潜能。
将人BM-MSCs暴露于10至250 mM的EtOH中。评估衰老相关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）。在经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。为研究沉默信息调节因子1（SIRT1）在EtOH诱导衰老中的作用，使用白藜芦醇（ResV）激活经EtOH处理的BM-MSCs中的SIRT1。
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细胞周期停滞。EtOH还增加了细胞内ROS以及衰老相关基因如p16INK4α和p21的表达。在经EtOH处理的BM-MSCs中证实了SIRT1水平下调并伴有成骨分化受抑制。ResV激活SIRT1通过降低衰老标志物和挽救受抑制的成骨作用部分抵消了EtOH的影响。
EtOH处理以剂量依赖方式诱导BM-MSCs过早衰老，这是EtOH损害成骨分化的原因。激活SIRT1可有效改善EtOH诱导的BMSCs衰老表型，并可能为临床预防或治疗酒精性骨质疏松症带来新策略。
乙醇（EtOH）处理以剂量依赖方式诱导骨髓间充质干细胞过早衰老，这是EtOH损害成骨分化的原因。激活SIRT1可有效改善EtOH诱导的衰老表型，这可能为临床治疗酒精性骨质疏松症带来新策略。
