Macrophages Play a Significant Role in P. gingivalis-Induced Bone-Loss

Chronic periodontitis is an inflammatory disease of the supporting tissues of teeth marked by infiltration of inflammatory cells into oral-mucosa, resulting in alveolar bone loss. Porphyromonas gingivalis has been strongly associated with progression and severity of disease. Macrophages play an essential role in chronic inflammatory diseases and studies have shown that macrophage numbers are elevated in periodontitis patients’ gingival biopsies. Objectives: To investigate the role of macrophages in P. gingivalis-induced periodontitis using murine periodontitis model based on Baker et al (1994)’s model. Methods: To investigate the role of local tissue macrophages in periodontitis, macrophages were depleted in submandibular lymph nodes and oral-mucosa of mice by subcutaneous injections of liposome-encapsulated clodronate. Results: Control mice (non-depleted) and macrophage-depleted mice were orally-infected with P.gingivalis. Control mice developed significant (p<0.001) bone loss compared to non-infected mice. Immunohistochemical staining and ELISA showed that infected mice had significantly increased numbers of macrophages in the gingiva and high titre P.gingivalis antigen specific IgG2b and IgG3 responses. Macrophage-depleted mice did not develop alveolar bone loss but did have a P.gingivalis antigen specific IgG2a and IgG2b response. The role of mature/activated macrophages and macrophage migration into tissues was investigated using GM-CSF-/- and Upa-/- mice, respectively. P.gingivalis infected GM-CSF-/- mice and Upa-/- mice had significantly less (p<0.001) bone loss compared with control-infected mice. Both GM-CSF-/- and Upa-/- infected mice also exhibited a weak P.gingivalis antigen specific IgG2b response. Conclusion: These studies show that the presence of mature/activated macrophages in the local tissue surrounding the oral-mucosa and the ability of macrophage to migrate into infected tissues have significant roles in the development of alveolar bone-loss in the murine periodontitis model. Furthermore, macrophages may also play a limited role in the immune response to P.gingivalis. This work may have implications in the development of novel therapies for chronic periodontitis.