Dataset Information

Analysis of the miRNA and mRNA involved in osteogenesis of adipose-derived mesenchymal stem cells.

ABSTRACT: Mesenchymal stem cells (MSCs) are bone marrow stromal cells capable of differentiating into different tissue types. Osteoblastic differentiation is a complex process that is critical for bone formation. An increasing number of studies have suggested that microRNAs (miRNAs) may serve important roles in various biological processes, including osteogenesis of MSCs. However, less is known about the participation of particular miRNAs in the osteogenic differentiation of adipose-derived stem cells (ADSCs). In order to identify functional miRNAs and the key genes involved in the osteogenesis of MSCs, the present study reconstructed a global network using data from the National Center for Biotechnology Information Gene Expression Omnibus. Meanwhile, gene ontology and pathway analysis were performed using the Cytoscape plug-in BinGO and the Database for Annotation, Visualization, and Integration Discovery, respectively. An miRNA-mRNA network composed of 72 mRNA and nine miRNA nodes advised by bioinformatics analysis was constructed. These mRNAs and miRNAs were predicted to be involved in the regulation of osteogenic differentiation of ADSCs according to the gene microarray. In the present study, six miRNAs (miR-143-3p, miR-135a-5p, miR-31-5p, miR-22-3p, miR-193b-3p and let-7i-5p) were observed to be highly associated with the osteogenesis of ADSCs, and dihydropyrimidinase like 3 was identified as a novel regulator in this process. These results provide support for further investigations into the management of bone regeneration-associated diseases.

SUBMITTER: Jia B

PROVIDER: S-EPMC6090261 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Analysis of the miRNA and mRNA involved in osteogenesis of adipose-derived mesenchymal stem cells.

Jia Bo B Zhang Zhaoqiang Z Qiu Xiaoling X Chu Hongxing H Sun Xiang X Zheng Xianghuai X Zhao Jianjiang J Li Qin Q

Experimental and therapeutic medicine 20180613 2

Mesenchymal stem cells (MSCs) are bone marrow stromal cells capable of differentiating into different tissue types. Osteoblastic differentiation is a complex process that is critical for bone formation. An increasing number of studies have suggested that microRNAs (miRNAs) may serve important roles in various biological processes, including osteogenesis of MSCs. However, less is known about the participation of particular miRNAs in the osteogenic differentiation of adipose-derived stem cells (AD ...[more]

PMID: 30116362

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Project description:Human adipose tissue‑derived stromal stem cells (HASCs) represent a promising regenerative resource for breast reconstruction and augmentation. However, the mechanisms involved in inducing its adipogenic differentiation remain to be fully elucidated. The present study aimed to comprehensively investigate the expression changes in mRNAs, microRNAs (miRNAs) and long non‑coding (lnc)RNAs during the adipogenic differentiation of HASCs, and screen crucial lncRNA‑miRNA‑mRNA interaction axes using microarray datasets GSE57593, GSE25715 and GSE61302 collected from the Gene Expression Omnibus database. Following pretreatment, differentially expressed genes (DEGs), miRNAs (DE‑miRNAs) or lncRNAs (DE‑lncRNAs) between undifferentiated and differentiated HASCs were identified using the Linear Models for Microarray data method. A protein‑protein interaction (PPI) network was constructed for the DEGs based on protein databases, followed by module analysis. The 'lncRNA‑miRNA‑mRNA' competing endogenous RNA (ceRNA) network was constructed based on the interactions between miRNAs and mRNAs, lncRNAs and miRNAs predicted by the miRWalk and lnCeDB databases. The underlying functions of mRNAs were predicted using the clusterProfiler package. In the present study, 905 DEGs, 36 DE‑miRNAs and 577 DE‑lncRNAs were screened between undifferentiated HASCs and differentiated adipocyte cells. PPI network analysis demonstrated that LEP may be a hub gene, which was also enriched in significant module 5. LEP was predicted to be involved in the Janus kinase‑signal transducer and activator of transcription signaling pathway, and the regulation of inflammatory response. The upregulation of LEP was regulated by downregulated hsa‑miRNA (miR)‑130b‑5p and hsa‑miR‑23a‑5p (or hsa‑miR‑302d‑3p). These miRNAs also respectively interacted with RP11‑552F3.9 (or RP11‑15A1.7), ultimately forming the ceRNA axes. In conclusion, the present study revealed that the RP11‑552F3.9 (RP11‑15A1.7)‑hsa‑miR‑130b‑5p/hsa‑miR‑23a‑5p (hsa‑miR‑302d‑3p)‑LEP interaction axes may be crucial for inducing the adipogenic differentiation of HASCs via involvement in inflammation.

Project description:Adipose-derived mesenchymal stem cells (adipose-derived MSCs, ASCs) possess the ability to differentiate into multiple tissue types and have immune-modulatory properties similar to those of MSCs from other origins. However, the regulation of the MSC-elicited immune-modulatory activity by specific microRNA (miRNA) mechanisms remains unexplored. Gene expression profiling with knowledge-based functional enrichment analysis is an appropriate approach for unraveling these mechanisms. This tool can be used to examine the transcripts and miRNA regulators that differentiate the rat tolerogenic orthotopic liver transplantation (OLT; DA liver into PVG) and rejection OLT (DA liver into LEW) models. In both models, the rejection reaction was observed on postoperative day 7?14 (rejection phase) but was overcome only by the PVG recipients. Thus, the global gene expression patterns of ASCs from spontaneously tolerant (PVG) and acute rejecting (LEW) rats in response to LPS activation were compared. In this study, we performed miRNA enrichment analysis based on the analysis of pathway, gene ontology (GO) terms and transcription factor binding site (TFBS) motif annotations. We found that the top candidate, miR-27, was specifically enriched and had the highest predicted frequency. We also identified a greater than 3-fold increase of miR-27b expression in the ASCs of tolerant recipients (DA to PVG) compared to those of rejecting recipients (DA to LEW) during the rejection phase in the rat OLT model. Furthermore, our data showed that miR-27b knockdown has a positive influence on the allosuppressive activity that inhibits T-cell proliferation. We found that miR-27 knockdown significantly induced the expression of CXCL12 in cultured ASCs and the expression of CXCL12 was responsible for the miR-27b antagomir-mediated inhibition of T-cell proliferation. These results, which through a series of comprehensive miRNA enrichment analyses, might be relevant for stem cell-based therapeutic applications in immunosuppressive function using ASCs.

Project description:Adipose-derived stromal/stem cells (ASCs) are multipotent in nature that can be differentiated into various cells lineages such as adipogenic, osteogenic, and chondrogenic. The commitment of a cell to differentiate into a particular lineage is regulated by the interplay between various intracellular pathways and their resultant secretome. Similarly, the interactions of cells with the extracellular matrix (ECM) and the ECM bound growth factors instigate several signal transducing events that ultimately determine ASC differentiation. In this study, RNA-sequencing (RNA-Seq) was performed to identify the transcriptome profile of osteogenic induced ASCs to understand the associated genotype changes. Gene ontology (GO) functional annotations analysis using Database for Annotation Visualization and Integrated Discovery (DAVID) bioinformatics resources on the differentially expressed genes demonstrated the enrichment of pathways mainly associated with ECM organization and angiogenesis. We, therefore, studied the expression of genes coding for matrisome proteins (glycoproteins, collagens, proteoglycans, ECM-affiliated, regulators, and secreted factors) and ECM remodeling enzymes (MMPs, integrins, ADAMTSs) and the expression of angiogenic markers during the osteogenesis of ASCs. The upregulation of several pro-angiogenic ELR+ chemokines and other angiogenic inducers during osteogenesis indicates the potential role of the secretome from differentiating ASCs in the vascular development and its integration with the bone tissue. Furthermore, the increased expression of regulatory genes such as CTNNB1, TGBR2, JUN, FOS, GLI3, and MAPK3 involved in the WNT, TGF-?, JNK, HedgeHog and ERK1/2 pathways suggests the regulation of osteogenesis through interplay between these pathways. The RNA-Seq data was also validated by performing QPCR on selected up- and down-regulated genes (COL10A1, COL11A1, FBLN, FERMT1, FN1, FOXF1, LAMA3, LAMA4, LAMB1, IGF1, WNT10B, MMP1, MMP3, MMP16, ADAMTS6, and ADAMTS14).

Dataset Information

Analysis of the miRNA and mRNA involved in osteogenesis of adipose-derived mesenchymal stem cells.

Publications

Analysis of the miRNA and mRNA involved in osteogenesis of adipose-derived mesenchymal stem cells.

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