Peri-implantitis, which is characterized by dense inflammatory infiltrates and increased osteoclast activity, can lead to alveolar bone destruction and implantation failure. miRNAs participate in the regulation of various inflammatory diseases, such as periodontitis and osteoporosis. Therefore, the present study aimed to investigate the differential expression of miRNAs in canine peri-implantitis and to explore the functions of their target genes. An miRNA sequence analysis was used to identify differentially expressed miRNAs in peri-implantitis. Under the criteria of a fold-change >1.5 and P<0.01, 8 up-regulated and 30 down-regulated miRNAs were selected for predictions of target genes and their biological functions. Based on the results of Gene Ontology (GO) and KEGG pathway analyses, these miRNAs may fine-tune the inflammatory process in peri-implantitis through an intricate mechanism. The results of quantitative real-time PCR (qRT-PCR) revealed that let-7g, miR-27a, and miR-145 may play important roles in peri-implantitis and are worth further investigation. The results of the present study provide insights into the potential biological effects of the differentially expressed miRNAs, and specific enrichment of target genes involved in the mitogen-activated protein kinase (MAPK) signaling pathway was observed. These findings highlight the intricate and specific roles of miRNAs in inflammation and osteoclastogenesis, both of which are key aspects of peri-implantitis, and thus may contribute to future investigations of the etiology, underlying mechanism, and 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. © 2018 American Society for Bone and Mineral Research.