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Differential long noncoding RNA/mRNA expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells

BACKGROUND: Mesenchymal stem cells (MSCs) are the most promising cell types for bone regeneration and repair due to their osteogenic potential. MSC differentiation is precisely regulated and orchestrated by the mechanical and molecular signals from the extracellular environment, involving complex pa...

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Autores principales: Zhang, Wenyuan, Dong, Rui, Diao, Shu, Du, Juan, Fan, Zhipeng, Wang, Fu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297123/
https://www.ncbi.nlm.nih.gov/pubmed/28173844
http://dx.doi.org/10.1186/s13287-017-0485-6
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author Zhang, Wenyuan
Dong, Rui
Diao, Shu
Du, Juan
Fan, Zhipeng
Wang, Fu
author_facet Zhang, Wenyuan
Dong, Rui
Diao, Shu
Du, Juan
Fan, Zhipeng
Wang, Fu
author_sort Zhang, Wenyuan
collection PubMed
description BACKGROUND: Mesenchymal stem cells (MSCs) are the most promising cell types for bone regeneration and repair due to their osteogenic potential. MSC differentiation is precisely regulated and orchestrated by the mechanical and molecular signals from the extracellular environment, involving complex pathways regulated at both the transcriptional and post-transcriptional levels. However, the potential role of long noncoding RNA (lncRNA) in the osteogenic differentiation of human MSCs remains largely unclear. METHODS: Here, we undertook the survey of differential coding and noncoding transcript expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells (BMSCs) using human whole transcriptome microarray. The key pathways, mRNAs, and lncRNAs controlling osteogenic differentiation of BMSCs were identified by further bioinformatic analysis. The role of lncRNA in the osteogenic differentiation of MSCs was verified by lncRNA overexpression or knockdown methods. RESULTS: A total of 1269 coding transcripts with 648 genes significantly upregulated and 621 genes downregulated, and 1408 lncRNAs with 785 lncRNAs significantly upregulated and 623 lncRNAs downregulated were detected along with osteogenic differentiation. Bioinformatic analysis identified that several pathways may be associated with osteogenic differentiation potentials of BMSCs, such as the MAPK signaling pathway, the Jak-STAT signaling pathway, the Toll-like receptor signaling pathway, and the TGF-beta signaling pathway, etc. Bioinformatic analysis also revealed 13 core regulatory genes including seven mRNAs (GPX3, TLR2, BDKRB1, FBXO5, BRCA1, MAP3K8, and SCARB1), and six lncRNAs (XR_111050, NR_024031, FR374455, FR401275, FR406817, and FR148647). Based on the analysis, we identified one lncRNA, XR_111050, that could enhance the osteogenic differentiation potentials of MSCs. CONCLUSIONS: The potential regulatory mechanisms were identified using bioinformatic analyses. We further predicted the interactions of differentially expressed coding and noncoding genes, and identified core regulatory factors by co-expression networks during osteogenic differentiation of BMSCs. Our results could lead to a better understanding of the molecular mechanisms of genes and lncRNAs, and their cooperation underlying MSC osteogenic differentiation and bone formation. We identified that one lncRNA, XR_111050, could be a potential target for bone tissue engineering. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-017-0485-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-52971232017-02-10 Differential long noncoding RNA/mRNA expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells Zhang, Wenyuan Dong, Rui Diao, Shu Du, Juan Fan, Zhipeng Wang, Fu Stem Cell Res Ther Research BACKGROUND: Mesenchymal stem cells (MSCs) are the most promising cell types for bone regeneration and repair due to their osteogenic potential. MSC differentiation is precisely regulated and orchestrated by the mechanical and molecular signals from the extracellular environment, involving complex pathways regulated at both the transcriptional and post-transcriptional levels. However, the potential role of long noncoding RNA (lncRNA) in the osteogenic differentiation of human MSCs remains largely unclear. METHODS: Here, we undertook the survey of differential coding and noncoding transcript expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells (BMSCs) using human whole transcriptome microarray. The key pathways, mRNAs, and lncRNAs controlling osteogenic differentiation of BMSCs were identified by further bioinformatic analysis. The role of lncRNA in the osteogenic differentiation of MSCs was verified by lncRNA overexpression or knockdown methods. RESULTS: A total of 1269 coding transcripts with 648 genes significantly upregulated and 621 genes downregulated, and 1408 lncRNAs with 785 lncRNAs significantly upregulated and 623 lncRNAs downregulated were detected along with osteogenic differentiation. Bioinformatic analysis identified that several pathways may be associated with osteogenic differentiation potentials of BMSCs, such as the MAPK signaling pathway, the Jak-STAT signaling pathway, the Toll-like receptor signaling pathway, and the TGF-beta signaling pathway, etc. Bioinformatic analysis also revealed 13 core regulatory genes including seven mRNAs (GPX3, TLR2, BDKRB1, FBXO5, BRCA1, MAP3K8, and SCARB1), and six lncRNAs (XR_111050, NR_024031, FR374455, FR401275, FR406817, and FR148647). Based on the analysis, we identified one lncRNA, XR_111050, that could enhance the osteogenic differentiation potentials of MSCs. CONCLUSIONS: The potential regulatory mechanisms were identified using bioinformatic analyses. We further predicted the interactions of differentially expressed coding and noncoding genes, and identified core regulatory factors by co-expression networks during osteogenic differentiation of BMSCs. Our results could lead to a better understanding of the molecular mechanisms of genes and lncRNAs, and their cooperation underlying MSC osteogenic differentiation and bone formation. We identified that one lncRNA, XR_111050, could be a potential target for bone tissue engineering. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-017-0485-6) contains supplementary material, which is available to authorized users. BioMed Central 2017-02-07 /pmc/articles/PMC5297123/ /pubmed/28173844 http://dx.doi.org/10.1186/s13287-017-0485-6 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zhang, Wenyuan
Dong, Rui
Diao, Shu
Du, Juan
Fan, Zhipeng
Wang, Fu
Differential long noncoding RNA/mRNA expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells
title Differential long noncoding RNA/mRNA expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells
title_full Differential long noncoding RNA/mRNA expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells
title_fullStr Differential long noncoding RNA/mRNA expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells
title_full_unstemmed Differential long noncoding RNA/mRNA expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells
title_short Differential long noncoding RNA/mRNA expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells
title_sort differential long noncoding rna/mrna expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297123/
https://www.ncbi.nlm.nih.gov/pubmed/28173844
http://dx.doi.org/10.1186/s13287-017-0485-6
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