Bioinformatics analysis on the differentiation of bone mesenchymal stem cells into osteoblasts and adipocytes

Abstract

The present study aimed to screen several differentially expressed genes (DEGs) and differentially expressed microRNAs (miRNAs) for two types of mesenchymal stem cell (MSC) differentiation. Bone morphogenetic protein 6 (BMP-6) and dexamethasone were used to induce MSCs towards osteoblastic differentiation or adipocytic differentiation. The t-test in the Bioconductor bioinformatics software tool was used to screen DEGs and differentially expressed miRNAs in the two samples. Subsequent gene ontology (GO) and pathway analyses on the DEGs were performed using the GO and Kyoto Encyclopedia of Genes and Genomes databases, respectively; potential target genes for the screened miRNAs were predicted using the TargetScan database. In addition, an interaction network between the DEGs and miRNAs was constructed. Numerous DEGs and miRNAs were screened during osteoblastic and adipocytic differentiation of MSCs. Important pathways, such as glutathione metabolism, pathogenic Escherichia coli infection and Parkinson's disease, and GO terms, including cytoskeletal protein binding and phospholipase inhibitor activity, were enriched in the screened DEGs from MSCs undergoing osteogenic differentiation and adipocytic differentiation. miRNAs, including miRNA (miR)-382 and miR-203, and DEGs, including neuronal growth regulator 1 (NEGR1), phosphatidic acid phosphatase 2B (PPAP2B), platelet-derived growth factor receptor alpha (PDGFRA), interleukin 6 signal transducer (IL6ST) and sortilin 1 (SORT1), were demonstrated to be involved in osteoblastic differentiation. In addition, the downregulated miRNAs (including miR-495, miR-376a and miR-543), the upregulated miR-106a, the upregulated DEGs, including enabled homolog (ENAH), polypeptide N-acetylgalactosaminyltransferase 1 and acyl-CoA synthetase long-chain family member 1, and the downregulated repulsive guidance molecule family member B and semaphorin SEMA7A were demonstrated to be involved in adipocytic differentiation. The results of the present study suggested that miRNAs (miR-203 and miR-382) and DEGs (NEGR1, PPAP2B, PDGFRA, IL6ST and SORT1) may serve pivotal functions in the osteoblastic differentiation of MSCs, whereas miR-495, which is also involved in osteoblast differentiation and had four targets, including NEGR1, miR-376a, miR-543 and ENAH may have crucial roles in adipocytic differentiation of MSCs.

Genome-Wide DNA Methylation Analysis during Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells

“…By GO term analysis, our results showed that the hypermethylated DMGs were enriched in the mesenchyme development, mesenchymal cell differentiation, stem cell differentiation, skeletal system development, and so on, while the hypomethylated DMGs were enriched in cell fate commitment, and so on. Research has reported that cytoskeletal protein binding was enriched in the differentially expressed genes (DEGs) in the process of MSC osteogenic differentiation and adipocytic differentiation [ 28 ]. Other studies analyzed the dataset of hMSCs differentiated into osteoblasts and these studies report that skeletal development is a specific example of a heterogeneous GO class [ 29 ].…”

Deep Sequencing Transcriptome Analysis of Murine Wound Healing: Effects of a Multicomponent, Multitarget Natural Product Therapy-Tr14

“…Serine protease inhibitor A3 is likely involved in controlling elastase activity and members of this family have been implicated in maintaining barrier functions (Hu et al, 2013 ). Micro RNA 543 (mir543) has been associated with mesenchymal stem cell differentiation, and thus may be related to changes in the cellular differentiation pathways (Xu et al, 2017 ).…”

Human umbilical cord mesenchymal stem cells-derived exosomes deliver microRNA-375 to downregulate ENAH and thus retard esophageal squamous cell carcinoma progression

“…These results together provide strong evidence that upregulated ENAH performs an oncogenic role in multiple types of cancers including ESCC. Additionally, ENAH has been verified as a target of miR-495 and is associated with adipose cell differentiation in MSCs [32]. A previous study demonstrated that downregulated ENAH suppressed proliferation and migration of GC cells [33].…”