circRNA Expression Profiles in Human Bone Marrow Stem Cells Undergoing Osteoblast Differentiation

Circular RNAs (circRNAs), which are produced by back-splicing events in genes, have emerged as factors in gene regulation and normal cellular homeostasis. They play an important role not only in normal development of tissues and organs, but also in disease pathogenesis and cell differentiation. However, the role of circRNAs in bone marrow stem cells (BMSCs) undergoing osteoblast differentiation remains largely unknown. We performed microarray analysis to determine the expression profiles of circRNAs during osteoblast differentiation. In total, 3938 circRNAs were upregulated and 1505 were downregulated in BMSCs at day 7 (D7) compared with day 0 (D0). About 95% of the differentially expressed circRNAs were derived from protein coding genes, and functional annotation analysis showed that the parental genes of differentially expressed circRNAs were enriched in osteogenesis-associated terms. We also analyzed the microRNA (miRNA) transcriptome since circRNAs have been suggested to interact with miRNAs. We then selected the circRNAs that were negatively correlated with miRNAs and possessed miRNA response elements to construct a circRNA-miRNA interaction network. Analysis of the hub nodes in the networks showed that the top five nodes were miRNAs. Some circRNAs were linked to miRNAs with osteogenic roles, indicating that these circRNAs potentially function in osteogenic differentiation of BMSCs. Moreover, we validated the expression of one hub miRNA, miR-199b-5p, and its linked circIGSF11. Silencing of circIGSF11 promoted osteoblast differentiation and increased the expression of miR-199b-5p. Our study suggests that circRNA-miRNA interaction actively contributes to the osteogenic differentiation of human BMSCs, suggesting potential avenues for further study.