Effect of Macrophage Activity and Age on Periodontal Disease in a Mouse Model
Background: Periodontal disease is an inflammatory disease that increases in prevalence with increasing age. The elderly demonstrate an elevated and dysregulated inflammatory response. Macrophages act as a key regulator of inflammation. The study aim was to evaluate the extent to which age-related changes and chemical inhibition in the macrophage affect periodontal disease in a mouse model.
Methods: Old (24 month) and young (3 month) mice were utilized for this study. Periodontal status was examined in mice at baseline. Periodontal disease was induced via Porphyromonas gingivalis (P. gingivalis) inoculated ligatures in old and young mice for 7 days. A second cohort had disease induced for 7 days, followed by ligature removal, and recovery for 7 additional days. Half the mice in each induction or recovery group were treated with Pexidartinib (PLX), which inhibits macrophage recruitment. Linear bone loss, alveolar bone volume, and macrophage quantification were examined by t test.
Results: PLX successfully inhibited macrophage numbers in all treatment groups. The young periodontal disease group had significantly more vertical bone loss (0.234±0.024mm) compared to the young periodontal disease PLX group (0.140±0.023mm)(p≤0.001) and less alveolar bone volume (0.460±0.016BV/TV) compared to the young periodontal disease PLX group (0.586±0.004BV/TV)(p≤0.001). The old periodontal disease group exhibited no difference in vertical bone loss (0.242±0.025mm) compared to the old periodontal disease PLX group (0.238±0.032mm)(p=0.825) and significantly less alveolar bone volume (0.536±0.030BV/TV) compared to the old periodontal disease PLX group (0.614±0.030BV/TV)(p≤0.01). The young recovery control group trended towards less vertical bone loss (0.170±0.020mm) compared to the young recovery + PLX group (0.190±0.011mm)(p=0.055) and had no difference in alveolar bone volume (0.557±0.015 BV/TV) compared to the young recovery PLX group (0.545±0.011 BV/TV)(p=0.131). The old recovery control group exhibited no difference in vertical bone loss (0.241±0.019mm) compared to the old recovery PLX group (0.218±0.035mm)(p=0.187) and had significantly less alveolar bone volume (0.567±0.021BV/TV) compared to the old recovery PLX group (0.617±0.023BV/TV)(p≤0.01).
PLX prevents periodontal disease induction in old and young groups and improves recovery in older age groups. The difference in response during recovery could suggest that there are age related changes in the macrophage that affect disease progression.