Abstract
BackgroundMesenchymal 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.MethodsHere, 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.ResultsA 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.ConclusionsThe 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.
Highlights
Mesenchymal stem cells (MSCs) are the most promising cell types for bone regeneration and repair due to their osteogenic potential
The profiling of differentially expressed mRNAs and long noncoding RNA (lncRNA) during osteogenic differentiation of Bone marrow mesenchymal stem cell (BMSC) To identify the differentially expressed lncRNAs and mRNAs during osteogenic differentiation of MSCs, we first applied the RVM t test to filter the genes that were differentially expressed, and the differentially expressed genes with 1.5-fold changes were selected according to the p value threshold false discovery rate (FDR) for subsequent analysis
A total of 1269 coding transcripts with differential expression were identified during osteogenic differentiation (p < 0.05, FDR < 0.05); of these, 648 were upregulated and 621 were downregulated in BMSCs at 7 days after osteogenic induction compared to the uninduced BMSCs (Additional file 1: Table S1)
Summary
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. The potential role of long noncoding RNA (lncRNA) in the osteogenic differentiation of human MSCs remains largely unclear. Bone marrow mesenchymal stem cells (BMSCs) are considered the gold standard for use in bone tissue regeneration among MSCs, and they are an important source of multipotent progenitor cells with self-renewal capacity that can differentiate into osteoblasts, chondrocytes, and adipocytes with great potential for clinic applications [1, 3]. BMSC 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 [4,5,6]. The particular functions of lncRNAs during osteogenic differentiation of human BMSCs still remain largely unclear
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