Altered microRNA expression profile in exosomes during osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.

Altered microRNA expression profile in exosomes during osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.
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人骨髓间充质干细胞成骨分化过程中外泌体中 microRNA 表达谱的改变。

DOI:
10.1371/journal.pone.0114627
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Wang YP
Wang YP
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Xu JF;Yang GH;Pan XH;Zhang SJ;Zhao C;Qiu BS;Gu HF;Hong JF;Cao L;Chen Y;Xia B;Bi Q;Wang YP

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microRNA (miRNA) 在成骨细胞分化中的生理作用仍然难以捉摸。使用含有 894 个人类成熟 miRNA 探针的 miRNA 阵列对从人骨髓来源的间充质干细胞 (BMSC) 培养物中分离的外泌体 miRNA 进行分析。当标准化为内源控制基因 RNU44 时,可以在从 BMSC 培养物上清液中分离的外泌体中检测到 79 个 miRNA (∼8.84%)。其中,与0天时的值相比,9个外泌体miRNA显着上调,4个miRNA显着下调(相对倍数>2,p<0.05),最大变化在1至7天。进一步验证了 5 种 miRNA(miR-199b、miR-218、miR-148a、miR-135b 和 miR-221),它们在不同时间点培养的 hBMSC 的单个外泌体样本中差异表达。 DIANA-mirPath 的生物信息分析表明,RNA 降解、mRNA 监视通路、Wnt 信号通路、RNA 转运是最显着的通路,富含与成骨分化相关的差异外泌体 miRNA 模式的分位数。这些数据表明外泌体 miRNA 是成骨细胞分化的调节因子。
The physiological role of microRNAs (miRNAs) in osteoblast differentiation remains elusive. Exosomal miRNAs isolated from human bone marrow-derived mesenchymal stem cells (BMSCs) culture were profiled using miRNA arrays containing probes for 894 human matured miRNAs. Seventy-nine miRNAs (∼8.84%) could be detected in exosomes isolated from BMSC culture supernatants when normalized to endogenous control genes RNU44. Among them, nine exosomal miRNAs were up regulated and 4 miRNAs were under regulated significantly (Relative fold>2, p<0.05) when compared with the values at 0 day with maximum changes at 1 to 7 days. Five miRNAs (miR-199b, miR-218, miR-148a, miR-135b, and miR-221) were further validated and differentially expressed in the individual exosomal samples from hBMSCs cultured at different time points. Bioinformatic analysis by DIANA-mirPath demonstrated that RNA degradation, mRNA surveillance pathway, Wnt signaling pathway, RNA transport were the most prominent pathways enriched in quantiles with differential exosomal miRNA patterns related to osteogenic differentiation. These data demonstrated exosomal miRNA is a regulator of osteoblast differentiation.
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