Lacking Interleukin-10 Regulates the Inflammasome-driven Alveolar Bone Loss

Abstract

Periodontitis triggers inflammation by pathogenic factors such as periodontal pathogenesis, which is exacerbated by the alveolar bone resorption, causing the teeth to fall out. It is known that inflammatory factors such as inflammatory cytokines spread throughout the body through blood circulation and other means and become a risk factor for developing systemic diseases such as diabetes and arteriosclerosis. Immune responses play an essential role in defending against invasion by pathogenic microorgan-isms and maintaining and improving homeostasis. IL-10, an inhibitory cytokine produced by immune cells, plays an essential role in preventing the development of au-toimmune diseases caused by excessive immune responses by directly acting on immune cells and inhibiting their activation. However, the role in the steady-state remains unclear. In this study, we investigated the effects of IL-10 on periodontal tissue under steady-state conditions using IL-10 knockout（KO）mice. Significant alveolar bone resorption was observed in IL-10KO mice. The localization of osteoclast-like cells in the alveolar fossa by TRAP staining. Real-time PCR revealed an increased RANKL/OPG ratio, confirming that bone resorption occurred compared with wild type mice. Moreover, significant inductions of pro-IL-1β, pro-IL-18, and IL-17A specific mRNA were detected, and protein levels were also induced in these mice’s gingiva. Further-more, a significant increase in the expression of NLRP3, a representative marker of the inflammasome, was also observed in IL-10KO. These results indicate that IL-10 defi-ciency leads to alveolar bone resorption even under steady-state conditions. In particular, the markedly formed inflammasome was suggested to induce not only periodontitis but also systemic diseases.