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

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0485-6) contains supplementary material, which is available to authorized users.

Mechanically cartilage-mimicking poly(PCL-PTHF urethane)/collagen nanofibers induce chondrogenesis by blocking NF–kappa B signaling pathway

“…6B) including cytokine-cytokine receptor, NF-kappa B, Toll-like receptor, TNF, Jak-STAT, Fc gamma R-mediated phagocytosis and phagosome. These pathways are involved with stem cell differentiation [35–37]. A heat map of the predicted target genes that were highly enriched in the 7 signaling pathways is shown in Fig.…”

Silencing of lncRNA AK045490 Promotes Osteoblast Differentiation and Bone Formation via β-Catenin/TCF1/Runx2 Signaling Axis

“…To date, many lncRNAs have been considered to regulate osteogenic differentiation [11]. Using human whole transcriptome microarray, Zhang et al profiled the expression and analyzed the functional network of lncRNAs during osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSC), in which a total of 1408 lncRNAs with 623 lncRNAs downregulating and 785 lncRNAs significantly upregulating were detected along with osteogenic differentiation [12]. In this study, we screened osteogenic-related lncRNAs in our established preosteoblast cell line [13] by performing mRNA and lncRNA microarray in combination with KEGG analysis and PCC co-expression analysis [7].…”

“…In MC3T3-E1 cells, knockdown of AK045490 significantly increased the expression of osteoblast differentiation marker genes (Alp, Ocn, and Col Iα1), the ALP activity and the formation of mineralized nodules (Figure 2), which were consistent with the phenomenon that the elevated AK045490 expression in bone tissue was accompanied by deteriorated bone microstructure and decreased bone formation in aging mice, as well as in OVX mice. Several canonical signaling pathways, such as the TGF-beta signaling pathway [14][15][16], the MAPK signaling pathway [17], the Hippo signaling pathway [18], the Notch signaling pathway [19], the Jak-STAT signaling pathway, and the Toll-like receptor signaling pathway [12], which are associated with the osteoblast differentiation, have been found to be closely related to lncRNAs. All of these findings indicated that lncRNAs are critical elements in osteoblast differentiation.…”

Extracellular vesicle-mediated transport of non-coding RNAs between stem cells and cancer cells: implications in tumor progression and therapeutic resistance

“…Since ncRNAs are central to gene regulation and cellular fates, it can be speculated that most of the EV-mediated regulatory roles elicited in cells/organs are mediated through ncRNAs (18,37). Indeed, ncRNAs are expressed in tissue-specific manner, precisely regulated and actively involved in variety of developmental processes (43)(44)(45)(46)(47)(48)(49)(50), and the lineage specific commitments of stem cells and the maintenance of their characteristic features such as pluripotency, self-renewal, differentiation, and efficiency of cellular reprogramming are largely regulated by ncRNAs (51)(52)(53)(54)(55)(56)(57)(58)(59)(60). Thus, the ncRNAs may govern the equilibrium between pluripotency and differentiation in stem cells, as well as lineage specific fate decisions (61,62).…”