Macrophage Phenotypes in a Mouse Model of Chronic Periodontitis

Objectives: The present study investigated the influence of Type2 diabetes mellitus (DM-II) on the local infiltration of macrophage subsets, proinflammatory (M1) and/or anti-inflammatory (M2), and the outcome of alveolar bone loss in a mouse model of ligature-induced periodontitis.
Methods: DM-II was induced in C57/BL mice (4-week-old male, n>4/group) by feeding high-fat diet, followed by streptozotocin injection (Luo et al. Metabolism 1998). After confirmation of DM-II development by a measurement of fasting blood glucose, ligature was placed on the left side maxillary molar for one week. After ligature removal, some groups were left without ligature for additional 2 weeks. Alveolar bone loss and immunohistochemical analyses of macrophages in the gingival tissue were performed.
Results: Systemically healthy control mice showed significant recovery from the ligature-induced alveolar bone loss during 2-w of the ligature-free period. However, in the DM-II group, little or no recovery of bone loss, along with persistent inflammation, was observed in the ligatured site, indicating that chronic inflammation was sustained in the context of DM-II/periodontitis, even after the removal of bacterial challenge. Very interestingly, the number of infiltrating macrophages increased in both control and DM-II mouse gingivae 1-w after ligature removal (p<0.05). Furthermore, the number of macrophages found in the ligatured site was significantly higher in the DM-II group compared to control. While the percentile of iNOS+/M1 cells among F4/80+ macrophages significantly diminished in the gingiva after ligature removal in both control and DM-II mice, CD206+/M2 cells maintained a high level in DM-II, but not control mice, suggesting that residual M2 macrophages may be associated with sustained periodontal inflammation and bone loss in DM-II mice.
Conclusions: Using a novel mouse model of DM-II periodontitis, we observed remarkably impaired periodontal bone regeneration by sustained chronic inflammation accompanied by M2 macrophages.