Abstract
The mechanisms underlying the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) remain unclear. In the present study, we aimed to identify the key biological processes during osteogenic differentiation. To this end, we downloaded three microarray data sets from the Gene Expression Omnibus (GEO) database: GSE12266, GSE18043 and GSE37558. Differentially expressed genes (DEGs) were screened using the limma package, and enrichment analysis was performed. Protein‐protein interaction network (PPI) analysis and visualization analysis were performed with STRING and Cytoscape. A total of 240 DEGs were identified, including 147 up‐regulated genes and 93 down‐regulated genes. Functional enrichment and pathways of the present DEGs include extracellular matrix organization, ossification, cell division, spindle and microtubule. Functional enrichment analysis of 10 hub genes showed that these genes are mainly enriched in microtubule‐related biological changes, that is sister chromatid segregation, microtubule cytoskeleton organization involved in mitosis, and spindle microtubule. Moreover, immunofluorescence and Western blotting revealed dramatic quantitative and morphological changes in the microtubules during the osteogenic differentiation of human adipose‐derived stem cells. In summary, the present results provide novel insights into the microtubule‐ and cytoskeleton‐related biological process changes, identifying candidates for the further study of osteogenic differentiation of the mesenchymal stem cells.
Highlights
Bone defects caused by bone trauma, tumours and infection are common and refractory diseases encountered in orthopaedic clinical settings
gene ontology (GO) analysis results showed that the up-regulated genes were mainly enriched in extracellular matrix organization, ossification, negative regulation of cell proliferation, vasculature development and positive regulation of cell death (Figure 2A and C), while the down-regulated genes were significantly enriched in cell division, spindle, midbody, metaphase plate congression and microtubules (Figure 2B and D)
Enrichment analysis of GO and KEGG was carried out to explore the interaction between Differentially expressed genes (DEGs)
Summary
Bone defects caused by bone trauma, tumours and infection are common and refractory diseases encountered in orthopaedic clinical settings. Increasing evidence shows that the osteogenic differentiation of MSCs involves a series of signalling pathways[7,8,9] such as BMP-SMAD,[10,11] WNT/Catenin,[12] Notch[13,14] and MAPK,,[15] and complex regulatory networks formed by interactions between these pathways.[16,17] Transcription factors, such as TWIST and MSX2, may be involved in the regulation of osteogenic differentiation.[18,19] In addition, certain physical stimuli promote the osteogenic differentiation of stem cells; for example, Heydari demonstrated that substrate stiffness and exposure to electromagnetic fields enhance the osteogenic potential of stem cells in the absence of chemical stimulation.[20,21,22] elucidation of the precise molecular mechanisms underlying osteogenesis is crucial to the development of bone tissue engineering applications and treatment strategies for bone defects. A total of 240 DEGs, 10 hub genes and one important biological process (microtubule-related) were identified, and the changes in microtubules may be a key factor in osteogenic differentiation of mesenchymal stem cells
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