Circ-FURIN Expression Enhances Osteoblast Differentiation In Dental Pulp Stem Cells Via SOX11 Signaling Pathway Sponging miR-125

Abstract

Background: Many studies have found that circRNA plays a part in osteoblast differentiation. However, its mechanism remains unknown. Methods: High-throughput sequencing was used to identifield the different expression of circRNA during osteogenic dental pulp stem cells (DPSCs) differentiation. Luciferase report analysis and RT-qPCR were used to clarify the expression and regulation relationship among circ-FURIN, miR-125 and SOX11. The heterotopic bone formation experiment was further used to confirm the osteoblast differentiation of DPSC with different expression of circ-FURIN, miR-125 and SOX11. Results: Study indicated that circ-FURIN expression remarkably increased during osteoblast differentiation, yet circ-FURIN knockdown suppressed it. Bioinformatics and luciferase results discovered that miR-125 is the downstream target of circ-FURIN. Furthermore, circ-FURIN upregulation decreased miR-125 expression. MiR-125 upregulation restored the promotion effect of circ-FURIN on osteogenic DPSC differentiation. Luciferase report analysis verified that SOX11 is miR-125 downstream target. miR-125 overexpression suppressed osteogenic DPSC differentiation through targeting SOX11. SOX11 overexpression restored miR-125 inhibitory effect on osteogenic DPSC differentiation. In vivo experiments with heterotopic bone model suggested that circ-FURIN overexpression has crucial function to enhance heterotopic bone formation. Conclusions: In summary, circ-FURIN enhances osteoblast DPSC differentiation via the SOX11 signaling pathway by sponging miR-125. These findings suggest a novel therapeutic target for osteoporosis treatment.