Plenty of studies indicate that macrophages, when as M1 phenotype, play a vital role in onset and development of periodontitis [34], while PGRN, identified as an endogenous antagonist of TNF-α by competitively binding to TNFRs, has potential positive action in autoimmune and inflammatory diseases, such as osteoarthritis [35] and periodontitis [30]. Here, TNF is linked to periodontitis.