A circular RNA derived from DAB1 promotes cell proliferation and osteogenic differentiation of BMSCs via RBPJ/DAB1 axis

Abstract

Osteogenesis (OS) is a type of differentiation that is of great importance for bone homeostasis. Increasing studies suggest circular RNAs (circRNAs) as pivotal regulators in OS. This study proposed to investigate mechanism mediated by circRNAs in OS. Based on GEO data and qRT-PCR assay, we found that circ-DAB1 (has_circ_0113689) was significantly up-regulated during osteogenic differentiation in human BMSCs. Overexpressing circ-DAB1 proliferation and osteogenic differentiation of BMSCs, whereas silencing circ-DAB1 elicited opposite functions. Subsequently, recombination signal-binding protein for immunoglobulin kappa J region (RBPJ), an important transcription factor in NOTCH pathway, was found to interact with DAB1 promoter while not to combine with circ-DAB1. Interestingly, circ-DAB1 overexpression could result in the increasing binding between RBPJ and DAB adaptor protein 1 (DAB1) promoter. Overexpressing circ-DAB1 upregulated RBPJ in BMSCs to induce DAB1 level. Further, we uncovered that circ-DAB1 upregulated RBPJ through sequestering miR-1270 and miR-944. Restoration experiments demonstrated that knocking down either RBPJ or DAB1 partially recovered BMSC proliferation and osteogenic differentiation that was suppressed by circ-DAB1 overexpression. Conclusively, circ-DAB1 promotes cell proliferation and osteogenic differentiation of BMSCs via NOTCH/RBPJ pathway.