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. 2017:2017:5045827.
doi: 10.1155/2017/5045827. Epub 2017 Apr 27.

The Critical Role of Long Noncoding RNA in Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells

Xiaoling Qiu  1 , Bo Jia  2 , Xiang Sun  2 , Weitao Hu  2 , Hongxing Chu  2 , Shuaimei Xu  1 , JianJiang Zhao  2
Affiliations

The Critical Role of Long Noncoding RNA in Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells

Xiaoling Qiu et al. Biomed Res Int. 2017.

Abstract

Objective. Long noncoding RNAs (lncRNAs) have been demonstrated to regulate many biological processes including differentiation. However, their role in osteogenic differentiation was poorly known. Materials and Methods. In this study, we first globally profiled the differentially expressed lncRNAs and mRNAs during osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMMSCs). Bioinformatics analysis was performed to further analyze these significantly changed molecules. Then the role of lncRNA ENST00000502125.2 in the osteogenic differentiation was determined. Results. A number of lncRNAs and mRNAs were significantly differentially expressed during hBMMSC osteogenic differentiation. Among them, 433 lncRNAs and 956 mRNAs were continuously upregulated, while 232 lncRNAs and 229 mRNAs were continuously downregulated. Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that carbohydrate derivative binding and complement and coagulation cascades were most correlated molecular function and pathway, respectively. Downregulation of lncRNA ENST00000502125.2 promoted the osteogenic differentiation of hBMMSCs, and opposite results were found when lncRNA ENST00000502125.2 was upregulated. Conclusions. lncRNAs play a critical role in the osteogenic differentiation of hBMMSCs and targeting lncRNA ENST00000502125.2 might be a promising strategy to promote osteogenic differentiation.

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Figures

Figure 1
Figure 1
(a) The expression levels of osteogenic markers ALP, OPN, and Osterix were significantly increased following osteogenic induction (∗∗p < 0.01). (b) The staining intensity of Alizarin Red S was increased following osteogenic induction. (c) Microarray analysis of gene expression during osteogenic differentiation of hBMMSCs.
Figure 2
Figure 2
(a) The hierarchical cluster analysis revealed the differentially expressed lncRNAs during the osteogenic differentiation of hBMMSCs. (b) The hierarchical cluster analysis revealed the differentially expressed mRNAs during the osteogenic differentiation of hBMMSCs. (c) qPCR validation of the significantly different expressed lncRNAs during the osteogenic differentiation of hBMMSCs. ∗∗indicates p < 0.01.
Figure 3
Figure 3
GO analysis of the significantly affected biological process, cellular component, and molecular function during osteogenic differentiation of hBMMSCs.
Figure 4
Figure 4
KEGG analysis of the significantly affected biological pathways during osteogenic differentiation of hBMMSCs.
Figure 5
Figure 5
(a) The expression level of lncRNA ENST00000502125.2 was decreased during osteogenic differentiation of hBMmSCs. (b) ShRNA could significantly downregulate lncRNA ENST00000502125.2 expression. (c) Lentivirus vectors could significantly upregulate lncRNA ENST00000502125.2 expression. (d) Downregulation of lncRNA ENST00000502125.2 promoted the ALP staining intensity, and vice versa (200x). (e) Downregulation of lncRNA ENST00000502125.2 promoted Alizarin Red S staining intensity, and vice versa (200x). ∗∗indicates p < 0.01.
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