MicroRNA-21 Deficiency Exacerbates Inflammation and Bone Loss in Periodontitis

Objectives: Periodontitis is one of the most prevalent inflammatory diseases, characterized by gingival inflammation and alveolar bone loss. MicroRNAs are important regulators of inflammation and involved in periodontitis pathogenesis. In this work, we aim to understand the roles of microRNA-21 in periodontitis.
Methods: Pro-inflammatory cytokine production from stimulated macrophage cells was tested by ELISA. A ligature-induced murine model for periodontitis has been utilized to determine the periodontal inflammation and tissue damage. Expression of pro-inflammatory cytokines in the gingivae of mice was determined by quantitative real-time PCR. Inflammatory bone loss was determined by measuring the distance from the cementoenamel junction to the alveolar bone crest (CEJ-ABC) in mice.
Results: MicroRNA-21 (MiR-21) is up-regulated in periodontitis patients and the mice that induced with periodontitis. MiR-21 expression is up-regulated in P. gingivalis LPS-stimulated macrophages. MiR-21 mimic inhibits the pro-inflammatory cytokine production by macrophages, while miR-21 deficiency elevates the production of pro-inflammatory cytokines. In a murine periodontitis model, ligation induced exacerbated gingival inflammation and alveolar bone loss in miR-21 deficient mice than their wild-type littermates. These results demonstrated the anti-inflammatory function of miR-21 in vitro and in vivo, indicating miR-21 could be an interventional target for the control of periodontitis.
Conclusions: We found the higher expression of miR-21 in periodontitis patients, ligated mice, and P. gingivalis LPS challenged cells, all suggesting the involvement of miR-21 in periodontitis. Our results showed that miR-21 down-regulate P. gingivalis LPS-induced inflammation, while miR-21 absence elevates pro-inflammatory cytokine production. These findings manifested the negative regulatory functions of miR-21 on pathogen-induced pro-inflammatory responses. Furthermore, in an in vivo periodontitis animal model, we demonstrated the protective roles of miR-21 on periodontitis progression. Our findings provide a potential immunotherapeutic method for periodontitis treatment.