Differential Expression Profiles of Circular RNAs During Osteogenic Differentiation of Mouse Adipose-Derived Stromal Cells

Osteogenesis is a complex and tightly regulated process. Circular RNAs (circRNAs) are covalently closed RNA molecules which are thought to play a significant role in bone metabolism. The purpose of this study was to investigate the expression and putative function of circRNAs during the osteogenic differentiation of mouse adipose-derived stromal cells (mADSCs). circRNA microarrays were used to determine differential circRNAs expression at different stages during osteogenesis of mADSCs. The most frequent differentially expressed circRNAs were selected by Venn analysis and clustered among the three induced groups. In addition, bioinformatic analyses (gene ontology, pathway, and co-expression network analysis) were used to further investigate these differentially expressed circRNAs. A total of 14,236 circRNAs were detected, of which 43 circRNAs (40 upregulated) were consistently altered at indicated time points during osteogenic differentiation of mADSCs. The exonic circRNAs represented a significantly larger proportion among the differentially expressed circRNAs compared to other types of circRNAs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes biological pathway analysis were performed to evaluate the functions of differentially expressed circRNAs during the osteogenic process. Our circRNA-miRNA co-expression network showed that miR-338-3p was correlated with upregulation of two circRNAs (mmu_circRNA_013422, mmu_circRNA_22566). Our data on circRNA expression profiles may provide valuable insight into circRNA function during osteogenic differentiation of mADSCs. Additionally, the circRNA-miRNA-mRNA pathways may provide information on novel mechanisms and targets for clinical investigations on bone formation and regeneration.