The Contribution of Macrophages in Old Mice to Periodontal Disease

Abstract

The prevalence of periodontal disease increases with age. Systemic inflammatory dysregulation also increases with age and has been reported to contribute to the myriad of diseases and conditions that become more prevalent with advanced age. As periodontal disease involves a dysregulated host inflammatory response, the age-related inflammatory dysregulation may contribute to the pathogenesis of periodontal disease in aging populations. However, our understanding of what drives the age-related inflammatory dysregulation is limited. Here, we investigate the macrophage and its contribution to periodontal disease in old and young mice using a ligature-induced periodontal disease model. We demonstrate that control old mice present with an aged periodontal phenotype, characterized by increased alveolar bone loss and increased local inflammatory cytokine expression compared to young mice. Macrophages were demonstrated to be present in the periodontium of old and young mice in equal numbers in controls, during disease induction, and during disease recovery. However, it appears age may have a detrimental effect on macrophage activity during disease recovery. Depletion of macrophages during disease recovery in old mice resulted in decreased inflammatory cytokines within the gingiva and decreased bone loss as measured by micro–computed tomography. In young mice, macrophage depletion during disease recovery had no beneficial or detrimental effect. Macrophage depletion during disease induction resulted in decreased disease severity similarly in young and old mice. Findings from this work support the diverse roles of macrophages in disease induction as well as the active roles of disease recovery, including the resolution of inflammation. Here, we conclude that age-related changes to the macrophage appear to be detrimental to the recovery from disease and may explain, in part, the age-related increase in prevalence of periodontal disease. Future studies examining the specific intrinsic age-related changes to the macrophage will help identify therapeutic targets.

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

“…Many studies have used the periodontitis model by placing ligatures inoculated with P. gingivalis around the teeth of the mice to induce massive local accumulation of periodontal pathogens [10,[177][178][179][180][181][182][183][184][185][186][187][188]190,191,194,195]. In a representative study using this model, Li and Amar [188] provided evidence that the mouse periodontal model involving a ligature inoculated with P. gingivalis exhibited a more adequate inflammatory response and greater periodontal tissue breakdown than the control group, which induced periodontitis by ligature alone.…”

Methylsulfonylmethane Increases the Alveolar Bone Density of Mandibles in Aging Female Mice

“…Since MSM is an anti-inflammatory compound, injection of MSM may have reduced the inflammatory events in the mandibular area and improved bone density. Clark et al reported depletion of macrophages in old mice resulted in decreased inflammatory cytokines within the gingiva and reduced bone loss ( Clark et al, 2021 ).…”

Polarized Macrophages in Periodontitis: Characteristics, Function, and Molecular Signaling

“…Clark et al. found that expressions of M1-related markers and proinflammatory cytokines and chemokines were significantly increased in elderly mice ( 42 ); found in their follow-up study of periodontal tissue, while elderly group and young group of mice in different period, there was no significant difference between the number of macrophages, but the elderly mice depleted macrophages more quickly in recovery stage ( 43 ). Although the depletion of macrophages stops inflammation earlier, it remains to be seen whether the process of tissue rebuilding and healing will also stop earlier.…”