Spontaneous up-regulation of SIRT1 during osteogenesis contributes to stem cells' resistance to oxidative stress.
Spontaneous up-regulation of SIRT1 during osteogenesis contributes to stem cells' resistance to oxidative stress.
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成骨过程中 SIRT1 的自发上调有助于干细胞抵抗氧化应激
DOI：
10.1002/jcb.26730
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发表时间：
2018-06
影响因子：
4
通讯作者：
He F
中科院分区：
文献类型：
--
作者：
Li M;Yan J;Chen X;Tam W;Zhou L;Liu T;Pan G;Lin J;Yang H;Pei M;He F
骨髓间充质干细胞（BM-MSCs）的成骨分化是骨形成的中心事件。然而，氧化应激对BM-MSC成骨具有有害影响。在这项研究中，我们假设氧化应激影响BM-MSC成骨的早期或晚期不同，其中沉默信息调节因子1（SIRT 1）发挥了关键作用。连续暴露于亚致死浓度的过氧化氢（H2 O2），范围从25 μM到100 μM，持续21天，导致BM-MSC成骨完全抑制。我们发现，用H2 O2处理7天抑制BM-MSCs向成骨细胞的谱系定型，如碱性磷酸酶活性（早期成骨的典型标志物）的显著降低所证明的。然而，适度的氧化应激并不影响晚期分化的BM-MSC，因为有相当水平的基质矿化（晚期成骨的典型标志物）。此外，我们观察到自发上调SIRT 1和细胞内的抗氧化酶，如超氧化物歧化酶2，过氧化氢酶，谷胱甘肽过氧化物酶1，这说明了增强抗氧化应激后成骨分化。白藜芦醇激活SIRT 1可挽救H2 O2对早期分化的BM-MSCs的影响，烟酰胺抑制SIRT 1可增强H2 O2对晚期分化的BM-MSCs的影响，表明SIRT 1介导的通路积极参与MSC成骨和抗氧化机制。我们的研究结果揭示了SIRT 1与BM-MSC成骨过程中抗H2 O2诱导的氧化应激的关系，这可能为保护MSC免受细胞外氧化应激提供新的策略。
Osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) is a central event in bone formation. However, oxidative stress has a deleterious impact on BM-MSC osteogenesis. In this study, we hypothesized that oxidative stress influenced BM-MSC osteogenesis differently in the early or late stages, in which silent information regulator type 1 (SIRT1) played a critical role. A continuous exposure to sublethal concentrations of hydrogen peroxide (H2O2), ranging from 25 μM to 100 μM for 21 days, resulted in the complete inhibition of BM-MSC osteogenesis. We found that a 7-day treatment with H2O2 inhibited the lineage commitment of BM-MSCs toward osteoblasts, as evidenced by a significant reduction of alkaline phosphatase activity (a typical marker for early osteogenesis). However, moderate oxidative stress did not affect late-differentiated BM-MSCs, as there were comparable levels of matrix mineralization (a typical marker for late osteogenesis). In addition, we observed a spontaneous up-regulation of SIRT1 and intracellular antioxidant enzymes such as superoxide dismutase 2, catalase, and glutathione peroxidase 1, which accounted for the enhanced resistance to oxidative stress upon osteogenic differentiation. Activation of SIRT1 by resveratrol rescued the effect of H2O2 on early-differentiated BM-MSCs and inhibition of SIRT1 by nicotinamide intensified the effect of H2O2 on late-differentiated BM-MSCs, indicating that the SIRT1-mediated pathway was actively involved in MSC osteogenesis and antioxidant mechanisms. Our findings uncovered the relationship between SIRT1 and resistance to H2O2-induced oxidative stress during BM-MSC osteogenesis, which could provide a new strategy for protecting MSCs from extracellular oxidative stress.
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在脱细胞细胞外基质上培养可增强人脐带源间充质干细胞的抗氧化特性。
DOI：
10.1016/j.msec.2015.12.090
发表时间：
2016-04-01
影响因子：
7.9
作者：
Liu, Xiaozhen;Zhou, Long;Chen, Xi;Liu, Tao;Pan, Guoqing;Cui, Wenguo;Li, Mao;Luo, Zong-Ping;Pei, Ming;Yang, Huilin;Gong, Yihong;He, Fan
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He, Fan
影响因子：
3.8
作者：
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通讯作者：
Lee JC
影响因子：
4.8
作者：
Byon, Chang Hyun;Javed, Amjad;Chen, Yabing
通讯作者：
Chen, Yabing
影响因子：
6.6
作者：
Olmos, Yolanda;Sanchez-Gomez, Francisco J.;Monsalve, Maria
通讯作者：
Monsalve, Maria
影响因子：
4.1
作者：
Pantovic, Aleksandar;Krstic, Aleksandra;Trajkovic, Vladimir
通讯作者：
Trajkovic, Vladimir