Histone Deacetylase Inhibitor Trichostatin A Promotes the Osteogenic Differentiation of Rat Adipose-Derived Stem Cells by Altering the Epigenetic Modifications on Runx2 Promoter in a BMP Signaling-Dependent Manner
Histone Deacetylase Inhibitor Trichostatin A Promotes the Osteogenic Differentiation of Rat Adipose-Derived Stem Cells by Altering the Epigenetic Modifications on Runx2 Promoter in a BMP Signaling-Dependent Manner
复制标题
组蛋白脱乙酰酶抑制剂曲古抑菌素 A 通过以 BMP 信号依赖方式改变 Runx2 启动子上的表观遗传修饰，促进大鼠脂肪干细胞的成骨分化
DOI：
10.1089/scd.2012.0105
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发表时间：
2013-01-01
影响因子：
4
通讯作者：
Ao, Yingfang
中科院分区：
文献类型：
--
作者：
Hu, Xiaoqing;Zhang, Xin;Ao, Yingfang
成体干细胞存在于许多类型的组织中，基于成体干细胞的再生医学在修复病变组织方面具有很大的前景。近年来，脂肪源性干细胞（ADSCs）被发现是一种有吸引力的替代骨髓干细胞（BMSCs）的组织工程骨再生。与骨髓间充质干细胞相比，脂肪间充质干细胞可以从脂肪组织中获得。然而，我们前期的研究发现了一个重要的现象，即骨髓间充质干细胞在体外具有比脂肪干细胞更强的成骨潜能。本研究旨在探讨其作用机制，提高脂肪干细胞的成骨潜能，促进骨组织再生。已有研究表明，表观遗传状态可能有助于成体干细胞的谱系特异性分化。我们观察到，在成骨诱导3天后，BMSCs的表观遗传变化比ADSCs大得多。Runx2是成骨细胞分化和骨形成所必需的转录因子。我们发现，骨髓间充质干细胞在成骨诱导后，Runx2启动子发生了更明显的表观遗传变化。这些结果表明，Runx2的表达，从而成骨的表观遗传调控参与。随后，我们使用组蛋白去乙酰化酶抑制剂，阿司他丁A（TSA），以促进ADSCs的成骨能力。结果表明，TSA通过改变Runx2启动子的表观遗传修饰，以骨形态发生蛋白信号依赖的方式促进大鼠ADSCs的成骨分化。
Adult stem cells reside in many types of tissues and adult stem cell-based regenerative medicine holds great promise for repair of diseased tissues. Recently, adipose-derived stem cells (ADSCs) were found to be an appealing alternative to bone marrow stem cells (BMSCs) for tissue-engineered bone regeneration. Compared with BMSCs, ADSCs can be easily and abundantly available from adipose tissue. However, our previous study has discovered an important phenomenon that BMSCs have greater osteogenic potential than ADSCs in vitro. In this study, we aimed to explore its mechanism and improve the osteogenic potential of ADSCs for bone tissue regeneration. It has been reported that the epigenetic states could contribute to lineage-specific differentiation of adult stem cells. We observed that the epigenetic changes of BMSCs were much greater compared with ADSCs after a 3-day osteogenic induction. Runt-related transcription factor 2 (Runx2) is essential for osteoblast differentiation and bone formation. We found that BMSCs underwent more obvious epigenetic changes on the Runx2 promoter than ADSCs after osteogenic induction. These results suggest the epigenetic regulation involvement in Runx2 expression, and thus osteogenesis. We subsequently used a histone deacetylase inhibitor, trichostatin A (TSA), to promote the osteogenesis capacity of ADSCs. The results showed that TSA promoted rat ADSCs osteogenic differentiation by altering the epigenetic modifications on the Runx2 promoter in a bone morphogenetic protein signaling-dependent manner.