LncRNA-OG Promotes the Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Under the Regulation of hnRNPK.

LncRNA-OG Promotes the Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Under the Regulation of hnRNPK.
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LncRNA-OG在hnRNPK调控下促进骨髓间充质干细胞成骨分化

DOI:
10.1002/stem.2937
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发表时间:
2019-03
期刊:
Stem cells (Dayton, Ohio)
影响因子:
--
通讯作者:
Shen H
Shen H
中科院分区:
其他
文献类型:
--
作者:
Tang S;Xie Z;Wang P;Li J;Wang S;Liu W;Li M;Wu X;Su H;Cen S;Ye G;Zheng G;Wu Y;Shen H

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骨髓间充质干细胞(BM-MSCs)是体内成骨细胞的主要来源,广泛用于干细胞治疗。以前,我们分析了BM-MSC成骨过程中的长链非编码RNA(lncRNA)表达谱,需要进一步研究以阐明lncRNA如何调节BM-MSC成骨。在此,我们使用定制的微阵列来确定成骨分化的第0天和第10天BM-MSC中的lncRNA表达谱。此外,我们发现了一种新的成骨相关lncRNA(lncRNA-OG),在此过程中上调。功能测定显示lncRNA-OG显著促进BM-MSC成骨。在机制上,lncRNA-OG与异质核核糖核蛋白K(hnRNPK)蛋白相互作用,以调节骨形态发生蛋白信号通路的激活。令人惊讶的是,hnRNPK通过促进lncRNA-OG启动子的H3 K27乙酰化来正向调节lncRNA-OG转录活性。因此,我们的研究揭示了一种新的lncRNA对BM-MSC成骨分化具有正功能,并提出了hnRNPK和lncRNA之间的新相互作用。干细胞2018干细胞2019;37:270-283 (A):在骨髓间充质干细胞成骨过程中,成骨相关长链非编码RNA与hnRNPK相互作用,促进骨形态发生蛋白家族的表达,最终促进成骨过程。(B)有趣的是,hnRNPK还可以结合成骨相关长链非编码RNA的启动子,通过增加组蛋白H3赖氨酸27乙酰化(H3 K27 ac)来促进成骨相关长链非编码RNA的转录活性。
Bone marrow‐derived mesenchymal stem cells (BM‐MSCs) are the main source of osteoblasts in vivo and are widely used in stem cell therapy. Previously, we analyzed long noncoding RNA (lncRNA) expression profiles during BM‐MSC osteogenesis, and further investigation is needed to elucidate how lncRNAs regulate BM‐MSC osteogenesis. Herein, we used customized microarrays to determine lncRNA expression profiles in BM‐MSCs on days 0 and 10 of osteogenic differentiation. In addition, we identified a novel osteogenesis‐associated lncRNA (lncRNA‐OG) that is upregulated during this process. Functional assays showed that lncRNA‐OG significantly promotes BM‐MSC osteogenesis. Mechanistically, lncRNA‐OG interacts with heterogeneous nuclear ribonucleoprotein K (hnRNPK) protein to regulate bone morphogenetic protein signaling pathway activation. Surprisingly, hnRNPK positively regulates lncRNA‐OG transcriptional activity by promoting H3K27 acetylation of the lncRNA‐OG promoter. Therefore, our study revealed a novel lncRNA with a positive function on BM‐MSC osteogenic differentiation and proposed a new interaction between hnRNPK and lncRNA. stem cells 2018 Stem Cells 2019;37:270–283 (A): During the osteogenesis of bone marrow‐derived mesenchymal stem cells, osteogenesis‐associated long noncoding RNA interacts with hnRNPK to promote the expression of bone morphogenetic proteins family, which ultimately promotes the process of osteogenesis. (B): Interestingly, hnRNPK can also bind to the promoter of osteogenesis‐associated long noncoding RNA, promoting osteogenesis‐associated long noncoding RNA transcriptional activity by increasing histone H3 lysine 27 acetylation (H3K27ac).
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