MiR-27a targets DKK2 and SFRP1 to promote reosseointegration in the regenerative treatment of peri-implantitis.

In the inflamed microenvironment of peri-implantitis, limited osteogenesis on the implant surface impedes well-established reosseointegration using current clinical therapies. MicroRNAs (miRNAs) function as potent molecular managers that may simultaneously regulate multiple endogenous processes such as inflammation and osteogenesis. The delivery of miRNAs may provide a way to effectively treat some diseases. In this study, we showed that miR-27a was differentially downregulated in samples from a canine peri-implantitis model. We found that overexpressing miR-27a positively regulated osteogenesis-angiogenesis coupling by ameliorating the TNF-α inhibition of bone formation in vitro. Mechanistically, we identified Dickkopf2 (DKK2) and secreted frizzled related protein 1 (SFRP1) as two essential direct miR-27a targets that were osteogenic and angiogenic. Furthermore, we constructed a miR-27a-enhanced delivery system to repair the bone defect around implants in a canine peri-implantitis model. The results demonstrated that the miR-27a-treated group could optimize new bone formation and reosseointegration in vivo. Our assay provides evidence that this strategy exerts therapeutic effects on peri-implantitis, suggesting that it represents a feasible method to maintain the stability and masticatory function of dental implants.