Metformin ameliorates the NLPP3 inflammasome mediated pyroptosis by inhibiting the expression of NEK7 in diabetic periodontitis

Abstract

ObjectivesTo investigate the underlying mechanism between diabetic periodontitis and NLR family pyrin domain containing 3 (NLRP3) inflammasome associated pyroptosis. DesignExperimental models of diabetes-associated periodontitis were implemented in db/db mice. We detected NLRP3 inflammasome related cytokines and gasdermin D (GSDMD) both in vitro and in vivo. We performed bioinformatics predictions based on microarray analysis using bone marrow derived macrophages (BMDMs). ResultsDiabetes-associated periodontitis mice exhibited the worst fasting glucose and alveolar bone destruction. GSDMD positive cells and NLRP3 inflammasome expression were augmented in gingival tissue, which were partly reversed by metformin. In vitro data suggested NLRP3 inflammasomes stimuli induced cell pyroptotic death and deletion of NLRP3 decreased GSDMD expression. We found a profile of differential lncRNAs expression and three co-expressed lncRNAs of nlrp3 and gsdmd in BMDMs. ConclusionsOur data show that NLRP3 mediated pyroptosis has a significant role in diabetes-associated periodontitis. The pyroptotic cell death may be the pivot reason of the deteriorated inflammation in this disease, which is ameliorated by metformin treatment. Moreover, the role of both NLRP3 and GSDMD may be regulated by lncRNA_1810058I24Rik, lncRNA_Gm12474 and lncRNA_Gm41514.