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鉴定源自股骨头坏死患者骨髓间充质干细胞成骨分化过程中表达的长非编码 RNA。

Identification of long non‑coding RNAs expressed during the osteogenic differentiation of human bone marrow‑derived mesenchymal stem cells obtained from patients with ONFH.

机构信息

Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.

Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

出版信息

Int J Mol Med. 2020 Nov;46(5):1721-1732. doi: 10.3892/ijmm.2020.4717. Epub 2020 Aug 31.

Abstract

Long non‑coding RNAs (lncRNAs) are crucial for the occurrence and development of numerous diseases. Although lncRNAs are involved in the biological activities of stem cells and play crucial roles in stem cell differentiation, the expression of specific lncRNAs during human bone marrow‑derived mesenchymal stem cell (hBMSC) osteogenic differentiation in osteonecrosis of the femoral head (ONFH) and their regulatory roles have not yet been fully elucidated. To the best of our knowledge, the present study is the first to characterize lncRNA expression profiles during hBMSC osteogenic differentiation in ONFH using microarray analysis and RT‑qPCR to confirm the microarray data. A total of 24 downregulated and 24 upregulated lncRNAs were identified and the results of RT‑qPCR were found to be consistent with those of microarray analysis. Bioinformatics analyses, using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, were conducted to explore the possible mechanisms and identify the signaling pathways that the lncRNAs are involved in. GO analysis revealed significant changes in the intracellular organelle, Ras protein signal transduction and transferase activity. KEGG pathway analysis revealed that the lncRNAs were closely associated with fatty acid metabolism, apoptosis and the TGF‑β signaling pathway. The overexpression of MAPT antisense RNA 1 (MAPT‑AS1) was found to promote osteogenesis and inhibit the adipogenesis of hBMSCs at the cellular and mRNA levels. On the whole, the findings of the present study identified the lncRNAs and their roles in hBMSCs undergoing osteogenic differentiation in ONFH and provide a new perspective for the pathogenesis of ONFH.

摘要

长链非编码 RNA(lncRNA)在许多疾病的发生和发展中至关重要。尽管 lncRNA 参与干细胞的生物活性,并在干细胞分化中发挥关键作用,但在股骨头坏死(ONFH)中,特定 lncRNA 在人骨髓间充质干细胞(hBMSC)成骨分化中的表达及其调节作用尚未完全阐明。据我们所知,本研究首次使用微阵列分析和 RT-qPCR 来验证微阵列数据,对 ONFH 中 hBMSC 成骨分化过程中的 lncRNA 表达谱进行了特征描述。鉴定出 24 个下调和 24 个上调的 lncRNA,并且 RT-qPCR 的结果与微阵列分析的结果一致。使用基因本体论(GO)和京都基因与基因组百科全书(KEGG)数据库进行生物信息学分析,以探索可能的机制并确定 lncRNA 参与的信号通路。GO 分析显示细胞内细胞器、Ras 蛋白信号转导和转移酶活性有明显变化。KEGG 通路分析表明,lncRNA 与脂肪酸代谢、细胞凋亡和 TGF-β 信号通路密切相关。MAPT 反义 RNA 1(MAPT-AS1)的过表达被发现可在细胞和 mRNA 水平上促进 hBMSC 的成骨分化并抑制其脂肪生成。总的来说,本研究的结果确定了 lncRNA 及其在 ONFH 中 hBMSC 成骨分化中的作用,为 ONFH 的发病机制提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c7f/7521548/742c93943e7d/IJMM-46-05-1721-g00.jpg

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