Mechanistically, NETosis is regulated by peptidylarginine deiminase-4 (PAD4)-mediated histone citrullination and this further confirms the role of NETosis in periodontitis – PAD4 KO mice displayed significant protection from periodontal bone loss compared to wild-type (WT) counterparts and in vivo pharmacologic delivery of CI-amidine to inhibit PAD4-mediated citrullination protected WT mice from ligature-induced periodontitis (25). This evidence concerns the gene PADI4 and periodontitis.