Targeting NLRP3 Inflammasome Reduces Age-Related Experimental Alveolar Bone Loss

Y. Zang, J. H. Song, S. H. Oh, J. W. Kim, M. N. Lee, X. Piao, J. W. Yang, O. S. Kim, T. S. Kim, S. H. Kim, J. T. Koh

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Abstract

The cause of chronic inflammatory periodontitis, which leads to the destruction of periodontal ligament and alveolar bone, is multifactorial. An increasing number of studies have shown the clinical significance of NLRP3-mediated low-grade inflammation in degenerative disorders, but its causal linkage to age-related periodontitis has not yet been elucidated. In this study, we investigated the involvement of the NLRP3 inflammasome and the therapeutic potential of NLRP3 inhibition in age-related alveolar bone loss by using in vivo and in vitro models. The poor quality of alveolar bones in aged mice was correlated with caspase-1 activation by macrophages and elevated levels of IL-1β, which are mainly regulated by the NLRP3 inflammasome, in periodontal ligament and serum, respectively. Aged mice lacking Nlrp3 showed better bone mass than age-matched wild-type mice via a way that affects bone resorption rather than bone formation. In line with this finding, treatment with MCC950, a potent inhibitor of the NLRP3 inflammasome, significantly suppressed alveolar bone loss with reduced caspase-1 activation in aged mice but not in young mice. In addition, our in vitro studies showed that the addition of IL-1β encourages RANKL-induced osteoclastogenesis from bone marrow–derived macrophages and that treatment with MCC950 significantly suppresses osteoclastic differentiation directly, irrelevant to the inhibition of IL-1β production. Our results suggest that the NLRP3 inflammasome is a critical mediator in age-related alveolar bone loss and that targeting the NLRP3 inflammasome could be a novel option for controlling periodontal degenerative changes with age.

Original languageEnglish
JournalJournal of Dental Research
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • aging
  • inflammasomes
  • inflammation
  • macrophages
  • osteoclasts
  • periodontitis

ASJC Scopus subject areas

  • Dentistry(all)

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    Zang, Y., Song, J. H., Oh, S. H., Kim, J. W., Lee, M. N., Piao, X., Yang, J. W., Kim, O. S., Kim, T. S., Kim, S. H., & Koh, J. T. (Accepted/In press). Targeting NLRP3 Inflammasome Reduces Age-Related Experimental Alveolar Bone Loss. Journal of Dental Research. https://doi.org/10.1177/0022034520933533