Canonical and noncanonical pyroptosis are both activated in periodontal inflammation and bone resorption.

Abstract

Pyroptosis has both a caspase-1-dependent canonical pathway and a caspase-4/-5/-11-dependent noncanonical pathway. They play an important role in inflammatory damage and related diseases. Canonical pyroptosis was reported to be involved in periodontitis. However, knowledge of caspase-4/-5/-11-dependent noncanonical pathway involvement remains limited. The aim of this study was to investigate the outcomes of pyroptosis inhibition on periodontitis as well as the possible mechanism, in order to provide a potential target for alleviating periodontitis. Human and rat periodontitis tissues were collected for immunohistochemistry (IHC). Micro-computed tomography was used to assess alveolar bone loss in experimental periodontitis model. Pyroptosis-related proteins were tested by western blot. propidium iodide staining and lactate dehydrogenase release were used to verify pyroptosis activation. RNA sequencing was applied to investigate the preliminary mechanism of the reduced periodontal inflammation induced by YVAD-CHO. Both canonical- and noncanonical-related proteins were detected in human and rat periodontitis tissue. The pyroptosis-inhibited group demonstrated less inflammatory response and bone absorption. In vitro, pyroptosis was activated by lipopolysaccharide and inhibited by YVAD-CHO. RNA sequencing demonstrated that the expression of A20 and IκB-ζ was increased and verified by western blot in vitro and IHC in vivo. These results suggest that inhibition of pyroptosis-reduced inflammation and alveolar bone resorption in periodontitis.