SEMA3B-AS1-inhibited osteogenic differentiation of human mesenchymal stem cells revealed by quantitative proteomics analysis

SEMA3B-AS1-inhibited osteogenic differentiation of human mesenchymal stem cells revealed by quantitative proteomics analysis
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定量蛋白质组学分析揭示SEMA3B-AS1抑制人间充质干细胞成骨分化

DOI:
10.1002/jcp.26776
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发表时间:
2019
影响因子:
5.6
通讯作者:
Zhaowei Teng
Zhaowei Teng
中科院分区:
生物学2区
文献类型:
--
作者:
Chen Zhang;Yun Zhu;Yugang Liu;Xiguang Zhang;Qiaoning Yue;Li Li;Yatang Chen;Sheng Lu;Zhaowei Teng

文献摘要

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人骨髓间充质干细胞(HMSCs)是一种成纤维样多能干细胞,具有向成骨细胞和软骨细胞分化的能力,在新骨形成和骨质疏松等骨修复相关的临床环境中显示出巨大的潜力。长非编码RNA(LncRNAs)已被证明在多种生物过程中发挥重要作用。在此,我们报道了一个调节hMSCs成骨的反义incRNA SEMA3B-AS1。SEMA3B-AS1是信号素家族Sema3b的近邻。慢病毒系统过表达SEMA3B-AS1可显著抑制hMSCs的增殖,同时减少成骨分化。利用一种名为等压标签的蛋白质组学技术进行相对和绝对定量,我们发现SEMA3B-AS1通过下调与肌动蛋白细胞骨架、焦点黏附和细胞外基质-受体相互作用相关的蛋白质的表达,而增加剪接体中蛋白质的表达,显著改变了成骨过程。综上所述,我们发现SEMA3B-AS1是控制hMSCs成骨的靶点。
Human mesenchymal stem cells (hMSCs) are fibroblastoid multipotent adult stem cells with capacities of differentiation into osteoblasts and chondrocytes and show great potential in new bone formation and bone repair‐related clinical settings, such as osteoporosis. Long noncoding RNAs (lncRNAs) have been demonstrated to play important roles in various biological processes. Here, we report an antisense lncRNA SEMA3B‐AS1 regulating hMSCs osteogenesis. SEMA3B‐AS1 is proximal to a member of the semaphorin family Sema3b. Overexpression of SEMA3B‐AS1 using the lentivirus system markedly inhibits the proliferation of hMSCs and meanwhile reduces osteogenic differentiation. Using a comprehensive proteomic technique named isobaric tag for relative and absolute quantitation, we found that SEMA3B‐AS1 significantly alters the process of osteogenesis through downregulating the expression of proteins involved in actin cytoskeleton, focal adhesion, and extracellular matrix–receptor interaction, while increasing the expression of proteins in the spliceosome. Collectively, we find that SEMA3B‐AS1 is a target for controlling osteogenesis of hMSCs.