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骨髓间充质干细胞在骨坏死相关的脂肪生成增加和成骨分化减少中的 lncRNA 表达谱。

LncRNA expression profiling of BMSCs in osteonecrosis of the femoral head associated with increased adipogenic and decreased osteogenic differentiation.

机构信息

Department of Orthopedics of the Second Hospital of Jilin University, Ziqiang Street 218, Changchun, Jilin, 130041, China.

Research Centre of the Second Hospital of Jilin University, Ziqiang Street 218, Changchun, Jilin, 130041, China.

出版信息

Sci Rep. 2018 Jun 14;8(1):9127. doi: 10.1038/s41598-018-27501-2.

Abstract

Long noncoding RNAs (lncRNAs) are critical gene expression regulators and are involved in several bone diseases. To explore the potential roles of lncRNAs in osteonecrosis of the femoral head (ONFH), we investigated for the first time the lncRNA expression profile of bone marrow mesenchymal stem cells (BMSCs) from patients with steroid-induced ONFH (SONFH) with microarray and bioinformatics analysis. A total of 1878 lncRNAs and 838 mRNAs were significantly up-regulated while 1842 lncRNAs and 1937 mRNAs were statistically down-regulated in the SONFH group compared with control group. The results validated by qRT-PCR were consistent with the microarray profiling data, especially involved in upregulation and downregulation of critical lncRNAs as well as mRNAs expression related to adipogenic and osteogenic differentiation. Pathway analyses revealed 40 signaling pathways with significant differences, especially the signaling pathways to regulate stem cell pluripotency. The CNC and ceRNA network indicated that lncRNA RP1-193H18.2, MALAT1 and HOTAIR were associated with abnormal osteogenic and adipogenic differentiation of BMSCs in the patients with SONFH. Our results suggest the lncRNA expression profiles were closely associated with the abnormal adipogenic and osteogenic transdifferentiation of BMSCs during the development of SONFH and explore a new insight into the molecular mechanisms of SONFH.

摘要

长链非编码 RNA(lncRNAs)是关键的基因表达调控因子,参与多种骨疾病。为了探讨 lncRNAs 在股骨头坏死(ONFH)中的潜在作用,我们首次通过微阵列和生物信息学分析研究了激素诱导性 ONFH(SONFH)患者骨髓间充质干细胞(BMSCs)的 lncRNA 表达谱。与对照组相比,SONFH 组中有 1878 个 lncRNAs 和 838 个 mRNAs 显著上调,而有 1842 个 lncRNAs 和 1937 个 mRNAs 显著下调。qRT-PCR 验证结果与微阵列分析数据一致,尤其是关键 lncRNAs 以及与成脂和成骨分化相关的 mRNAs 表达的上调和下调。通路分析显示有 40 个信号通路存在显著差异,尤其是调控干细胞多能性的信号通路。CNC 和 ceRNA 网络表明,lncRNA RP1-193H18.2、MALAT1 和 HOTAIR 与 SONFH 患者 BMSCs 异常成脂和成骨分化有关。我们的结果表明,lncRNA 表达谱与 SONFH 发展过程中 BMSCs 的异常成脂和成骨转分化密切相关,并为 SONFH 的分子机制研究提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca21/6002551/45e7213be5bb/41598_2018_27501_Fig1_HTML.jpg

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