MiRNA-218 regulates osteoclast differentiation and inflammation response in periodontitis rats through Mmp9.

Periodontitis is a multiple infection and inflammatory disease featured by connective tissue homeostasis loss, periodontal inflammation, and alveolar bone resorption. MicroRNAs (miRNAs) are involved in the mediation of a large scale of pathological processes. Here, we show that miRNA-218 provides protective effect on periodontitis via regulation of matrix metalloproteinase-9 (Mmp9). This pathway is aberrant in periodontium from rats with periodontitis and human periodontal ligament progenitor cells stimulated by lipopolysaccharide, with downregulation of miR-218 and higher levels of Mmp9 compared with periodontium from healthy rats and cells without stimulation. Overexpression of miR-218 can suppress the degradation of Collagen Types I and IV and dentin sialoprotein (DSP), attenuate osteoclast formation, and inhibit the secretion of proinflammatory cytokines. On the other hand, overexpression of Mmp9 promotes the degradation of Collagen Types I and IV and DSP as well as RANKL-induced osteoclast formation and elevates inflammatory factors levels. Furthermore, the inhibitory effect of miR-218 was prevented by rescuing the Mmp9 expression. In addition, we also have showed that miR-218 was able to attenuate bone resorption and inflammation in a periodontitis rat model. Collectively, our findings therefore suggest that miR-218 acts as a protective role in periodontitis through the regulation of Mmp9.