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

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?? 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.

SUBMITTER: Li T

PROVIDER: S-EPMC7521548 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Li Tao T Xiao Ke K Xu Yingxing Y Ren Yuanzhong Y Wang Yingzhen Y Zhang Haining H Weng Xisheng X Jiang Yaping Y

International journal of molecular medicine 20200831 5

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 ...[more]

PMID: 32901839

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Project description:Long non?coding RNAs (lncRNAs) are a specific group of RNA molecules that do not encode proteins. They have been shown to serve important regulatory functions in various biological and cell differentiation processes. However, the potential functions and regulatory mechanisms of lncRNAs that are associated with the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) remain to be elucidated. The present study aimed to investigate lncRNAs that are differentially expressed during the osteogenic differentiation of hBMSCs, along with the potential functions of those lncRNAs. To this end, three groups of hBMSCs were stimulated to undergo osteogenic differentiation for 7 days. Known lncRNAs, unknown lncRNAs and mRNAs that demonstrated differential expression prior to and following the osteogenic differentiation of hBMSCs were screened using lncRNA high?throughput sequencing. In addition, 12 lncRNAs were selected for reverse transcription?quantitative polymerase chain reaction (RT?qPCR) validation of the accuracy of the sequencing results. The potential functions and possible targets of the differentially expressed lncRNAs were analyzed using bioinformatics technologies (gene ontology, Kyoto Encyclopedia of Genes and Genomes and gene co?expression network analysis). In total, 64 lncRNAs were differentially expressed by at least two?fold in hBMSCs prior to and following osteogenic differentiation; these included seven known lncRNAs (two upregulated and five downregulated lncRNAs) and 57 unknown lncRNAs (35 upregulated and 22 downregulated lncRNAs). In addition, 409 mRNAs (257 upregulated and 152 downregulated mRNAs) were differentially expressed by at least two?fold. The RT?qPCR results obtained for 12 selected differentially expressed lncRNAs were consistent with the sequencing results. The gene co?expression network analysis of lncRNAs and mRNAs demonstrated that four lncRNAs (ENSG00000238042, lnc_1269, lnc_1369 and lnc_1708) may serve important roles in the osteogenic differentiation of hBMSCs. In conclusion, during the osteogenic differentiation of hBMSCs, the lncRNA expression profile changed significantly; certain of the observed differentially expressed lncRNAs may be derived from protein?coding genes and may serve important roles in osteogenic differentiation.

Dataset Information

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

Publications

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

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