Dental implant has become a preferable choice to restore the missing tooth in the past few decades for functional and esthetic purposes [1]. However, peri-implantitis has become prevalent accompanying the exponential growth of dental implant procedures [2, 3]. Peri-implantitis is indicated by infection of implant surrounding soft tissues and bone loss, resulting in implant failure eventually [4,5,6]. The host immune and inflammatory responses caused by plaques on implant surface are crucial in the pathogenesis of peri-implantitis [2, 7, 8]. However, current treatment available for peri-implantitis is not satisfactory due to the lack of understanding of the mechanism of peri-implantitis pathogenesis.

Receptor activator of nuclear factor-kappa B (RANK) and its ligand RANKL and the decoy receptor osteoprotegerin (OPG) are central regulators of osteoclast development and essential for osteoimmunology [9,10,11,12]. Recent study showed that RANKL/OPG ratio was significantly increased in the gingival tissues surrounding mini-implants in the rat model with Porphyromonas gingivalis LPS inductions [13]. Moreover, anti-RANKL antibody was approved for the treatment of osteoporosis, and it showed inhibition of bone loss in rodent experimental periodontitis models [14,15,16,17]. Our previous study showed that administration of anti-RANKL antibody directly to the gingival of rat experimental periodontitis model can significantly reduce gingival sRANKL expression and of bone resorption [18]. However, the effects of anti-RANKL antibody on peri-implantitis have not been investigated.

MicroRNAs (miRs) are small non-coding RNA molecules found in plants, animals, and some viruses, functioning in RNA silencing and post-transcriptional regulation of gene expression [19,20,21]. Recent studies showed that miRs are important regulators in periodontitis [21,22,23]. Our previous studies demonstrated that miR-146a regulated the cytokine secretion in human gingival fibroblasts and periodontal ligament cells and inhibits inflammatory cytokine production in B cells through directly targeting IRAK1, suggesting a regulatory role of miR-146a in immune-mediated periodontal inflammation [24]. However, the role of miR-146a in peri-implantitis remains unknown.