Identification of key genes and pathways associated with osteogenic differentiation of adipose stem cells

Abstract

Adipose stem cells (ASCs) are considered a great alternative source of mesenchymal stem cells (MSCs) and have shown great promise on tissue engineering and regenerative medicine applications, including bone repair. However, the underlying mechanisms regulating the osteogenic differentiation of ASCs remain poorly known. Gene expression profiles of GSE63754 and GSE37329 were downloaded from gene expression omnibus database. R software and Bioconductor packages were used to compare and identify the differentially expressed genes (DEGs) before and after ASC osteogenic differentiation. The common significant DEGs between GSE63754 and GSE37329 were then subjected to gene ontology (GO) enrichment analysis, ingenuity pathway analysis (IPA), and protein-protein interactions (PPIs) networks analysis. One of the central node genes FOXO1 was selected for further investigation. A total of 142 up- and 69 downregulated genes were aberrantly expressed in both GSE63754 and GSE37329. GO analysis revealed that these DEGs were associated with extracellular matrix organization, proteinaceous extracellular matrix, and Wnt-protein binding. IPA analysis showed that canonical pathways, such as FXR/RXR activation, adipogenesis pathway, and LXR/RXR activation, were involved in regulating osteogenic differentiation of ASCs. A total of three subnetworks and 39 nodes were identified with PPI network and MCODE plugin. Moreover, suppression of one central node gene FOXO1 inhibited the osteogenic differentiation of ASCs. Our study provides a registry of genes and pathways that play important roles in regulating osteogenic differentiation of ASCs, which might have potential therapeutic applications in bone regeneration and bone tissue engineering.

Adipogenesis, Osteogenesis, and Chondrogenesis of Human Mesenchymal Stem/Stromal Cells: A Comparative Transcriptome Approach

“…Comparison of datasets could allow the identification of key genes presented in different osteogenic differentiation protocols ( Yang et al, 2019 ) which may indicate an essential role in the differentiation process. Beside that, re-analysis of microarray data from osteogenic differentiated adipose derived-MSC ( Berdasco et al, 2012 ; Daniunaite et al, 2015 ) showed that 142 and 69 genes were up and downregulated, respectively, in both datasets ( Zhao et al, 2018 ). GO and pathway analysis of DEG indicated that they were enriched in terms associated with “ECM organization,” “angiogenesis,” “Wnt protein binding,” “FXR/RXR activation,” and “adipogenesis pathway,” among others.…”

The Role of Omega-3 Polyunsaturated Fatty Acids from Different Sources in Bone Development

“…To better understand the impact of n-3 PUFAs on the transcriptome of the developing bone, we performed RNA-seq analysis of the bones of mice whose PUFA intake originated from different dietary sources. Although a few studies have used RNA-seq analysis to reveal the DE genes in skeletal tissue [45][46][47], as far as we know, this is the first study that uses RNA-seq to study the effect of dietary n-3 PUFAs on bone transcriptome in vivo.…”

Adipose Stem Cell Translational Applications: From Bench-to-Bedside

“…ASCs have self-renewal property as demonstrated by the Colon Forming Unit formation (CFU-F) assay [ 39 , 40 , 41 , 66 ]. They have multipotency property, as they have the capability to differentiate toward different mesenchymal cell lineages [ 39 , 65 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 ]. Interestingly, ASCs also have a higher responsiveness to inducers of non-mesenchymal cell lineages differentiation [ 39 , 65 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 ].…”

“…The osteogenic differentiation of ASCs, may be achieved by using inducing osteogenic factors (e.g., dexamethasone, ascorbic acid/ascorbate 2-phosphate, and β-glycerophosphates, vitamin D3, transforming growth factor-β and bone morphogenetic proteins), in growth culture medium. As a consequence ASCs express early osteogenic markers (alkaline phosphatase and BMPII) and later osteogenic markers (osteocalcin, osteogenic transcription factor Runx2, osteonectin, osteopontin, bone morphogenic protein-2, and Osterix) [ 41 , 73 , 101 , 111 ].…”