Aspirin-induced attenuation of adipogenic differentiation of bone marrow mesenchymal stem cells is accompanied by the disturbed epigenetic modification
Aspirin-induced attenuation of adipogenic differentiation of bone marrow mesenchymal stem cells is accompanied by the disturbed epigenetic modification
复制标题
阿司匹林诱导的骨髓间充质干细胞成脂分化减弱伴随着表观遗传修饰的紊乱
DOI：
10.1016/j.biocel.2018.02.010
复制
发表时间：
2018
影响因子：
4
通讯作者：
Zhang B
中科院分区：
文献类型：
--
作者：
Zhan Yuanbo;He Zhiwei;Liu Xinpeng;Miao Nan;Lin Feng;Xu Wenxia;Mu Haibin;Yuan Mengtong;Cao Xiaofang;Jin Han;Liu Zhongshuang;Li Ying;Zhang Bin;Zhan Yuanbo;Mu Sen;Zhang Bin;Zhang B
阿司匹林对骨髓间充质干细胞（BMSCs）的成骨分化有促进作用。然而，研究人员并没有过多考虑其对BMSCs成脂分化的影响。本研究分析阿司匹林对骨髓间充质干细胞成脂分化的影响。为了检测阿司匹林对BMSCs成脂分化的影响是否与表观遗传修饰紊乱有关，研究了组蛋白去乙酰化酶（HDAC）的表达，HDAC和HAT的活性，以及组蛋白H3乙酰化和H3k9乙酰化的改变。此外，为了进一步探索和理解阿司匹林与HDAC之间的结合模式，我们尝试借助计算机对接研究来确定阿司匹林与HDAC之间的相互作用。结果表明，阿司匹林可抑制BMSCs成脂。HDAC活性、组蛋白H3乙酰化和H3k9乙酰化水平在成脂分化过程中均下调，阿司匹林可逆转这些下调。此外，HDAC亚型在这些进展中具有不同的表达模式。在骨髓间充质干细胞成脂分化过程中，加入阿司匹林后HDAC9的表达呈剂量依赖性增加。对接研究表明，HDAC 9与阿司匹林之间存在高亲和力，提示HDAC 9可能在阿司匹林抑制脂肪生成的过程中发挥重要作用。HDAC异构体的作用机制尚需进一步研究，以了解阿司匹林及其抑制成脂分化的作用机制，为阿司匹林在组织再生中的临床应用奠定基础。
Aspirin has positive effects on bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation. However, researchers did not give much thought to its effect on BMSCs adipogenic differentiation. Here, we analyzed the effect of aspirin on the BMSCs adipogenic differentiation. To detect whether the effect of aspirin on the adipogenic differentiation of BMSCs is associated with the disturbed epigenetic modification, the expression of histone deacetylases (HDACs), activity of HDACs and HAT, global histone H3 acetylation and H3k9 acetylation alterations were investigated. Moreover, to further explore and understand the binding mode between aspirin and HDACs, an attempt was made to identify the interaction between aspirin and the HDACs with the aid ofin silicodocking study. The results showed that aspirin could induce inhibition of BMSCs adipogenesis. The level of HDAC activity, global histone H3 acetylation, and H3k9 acetylation were all down regulated during adipogenic differentiation, and aspirin can reverse these decreases. Furthermore, the HDAC isoforms have different expression patterns in those progresses. The expression of HDAC9 was increased in a does-dependent manner when aspirin was introduced during BMSCs adipogenic differentiation. Docking study showed that high affinity of HDAC9 to aspirin was existed, suggesting that HDAC9 may has an important role in the process of aspirin-induced suppression of adipogenesis. Further studies are needed to define the intricate mechanisms of the HDAC isoforms, and all of these enable us to understand aspirin and its efficacy of inhibition of adipogenic differentiation and pave the way to aspirin clinical using for the tissue regenerating.