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Hyperglycaemia‐associated macrophage pyroptosis accelerates periodontal inflamm‐aging
Author(s) -
Zhao Pengfei,
Yue Ziqi,
Nie Lulingxiao,
Zhao Zhihao,
Wang Qian,
Chen Jiao,
Wang Qi
Publication year - 2021
Publication title -
journal of clinical periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.456
H-Index - 151
eISSN - 1600-051X
pISSN - 0303-6979
DOI - 10.1111/jcpe.13517
Subject(s) - pyroptosis , senescence , macrophage , inflammasome , microbiology and biotechnology , periodontitis , medicine , inflammation , in vitro , immunology , biology , biochemistry
Aim Pyroptosis and inflamm‐aging have been newly identified to be involved in diabetic periodontitis. This study aimed to elucidate whether macrophage pyroptosis plays a role in periodontal inflamm‐aging by impacting the senescence of fibroblasts, as well as the potential mechanism via NLR family CARD domain‐containing protein 4 (NLRC4) phosphorylation. Materials and methods Diabetes was induced in mice using streptozotocin. Periodontal pyroptosis and senescence were detected using immunohistochemical analysis. Prior to evaluating senescence in human gingival fibroblasts cultured with conditioned medium derived from macrophages, RAW 264.7 macrophages were confirmed to undergo pyroptosis by scanning electron microscopy and gasdermin D (GSDMD) detection. The NLRC4‐related pathway was examined under hyperglycaemic conditions. Results Our data showed that macrophage pyroptosis induced the expression of senescent markers in vivo and in vitro. Importantly, clearance of pyroptotic macrophages rescued senescence in fibroblasts. Furthermore, GSDMD activation and pyroptosis in hyperglycaemia were found to be mediated by NLRC4 phosphorylation. Conclusions Hyperglycaemia could initially induce macrophage pyroptosis and lead to cellular senescence, thereby critically contributing to periodontal pathogenesis in diabetes. In particular, NLRC4 phosphorylation could be a potential therapeutic target for the inhibition of this process.