Interferon activated gene 204 protects against bone loss in experimental periodontitis

Background Periodontal destruction can be the result of different known and yet‐to‐be‐discovered biological pathways. Recent human genetic association studies have implicated interferon‐gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) with high periodontal interleukin (IL)‐1β levels and more destructive disease, but mechanistic evidence is lacking. Here, we sought to experimentally validate these observational associations and better understand IFI16 and AIM2's roles in periodontitis. Methods Periodontitis was induced in Ifi204–/– (IFI16 murine homolog) and Aim2–/– mice using the ligature model. Chimeric mice were created to identify the main source cells of Ifi204 in the periodontium. IFI16‐silenced human endothelial cells were treated with periodontal pathogens in vitro. Periodontal tissues from Ifi204–/– mice were evaluated for alveolar bone (micro‐CT), cell inflammatory infiltration (MPO+ staining), Il1b (qRT‐PCR), and osteoclast numbers (cathepsin K+ staining). Results Ifi204‐deficient mice> exhibited >20% higher alveolar bone loss than wild‐type (WT) (P