Copyright © 2019 Mi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fracture healing is a complex process involving various cell types, cytokines, and mRNAs. Here, we report the roles of the circRNA AFF4/miR-7223-5p/PIK3R1 axis during fracture healing. We found that increased expression of PIK3R1 during fracture healing is directly associated with augmented proliferation and decreased apoptosis of MC3T3-E1 cells. Furthermore, miR-7223-5p targeted PI3KR1 and inhibited MC3T3-E1 proliferation while promoting apoptosis. CircRNA AFF4 acted as a sponge of miR-7223-5p, thereby promoting MC3T3-E1 cell proliferation and inhibiting apoptosis. Local injection of circRNA AFF4 into femoral fracture sites promoted fracture healing in vivo while the injection of miR-7223-5p delayed healing. These findings suggest that CircRNA AFF4 promotes fracture healing by targeting the miR-7223-5p/PIK3R1 axis, and suggests miR-7223-5p, CircRNA AFF4, and the miR-7223-5p/PIK3R1 axis are potential therapeutic targets for improving fracture healing.