PMID- 32480011 OWN - NLM STAT- MEDLINE DCOM- 20201029 LR - 20201029 IS - 1879-1506 (Electronic) IS - 0003-9969 (Linking) VI - 116 DP - 2020 Aug TI - Metformin ameliorates the NLPP3 inflammasome mediated pyroptosis by inhibiting the expression of NEK7 in diabetic periodontitis. PG - 104763 LID - S0003-9969(20)30141-2 [pii] LID - 10.1016/j.archoralbio.2020.104763 [doi] AB - OBJECTIVES: To investigate the underlying mechanism between diabetic periodontitis and NLR family pyrin domain containing 3 (NLRP3) inflammasome associated pyroptosis. DESIGN: Experimental 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). RESULTS: Diabetes-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. CONCLUSIONS: Our 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. CI - Copyright (c) 2020. Published by Elsevier Ltd. FAU - Zhou, Xinyi AU - Zhou X AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, 3rd Section S Renmin Road, 14#, Chengdu, PR China; Department of Implantology, West China Hospital of Stomatology, Sichuan University, PR China. FAU - Wang, Qian AU - Wang Q AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, 3rd Section S Renmin Road, 14#, Chengdu, PR China; Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, PR China. FAU - Nie, Lulingxiao AU - Nie L AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, 3rd Section S Renmin Road, 14#, Chengdu, PR China; Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, PR China. FAU - Zhang, Peng AU - Zhang P AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, 3rd Section S Renmin Road, 14#, Chengdu, PR China; Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, PR China. FAU - Zhao, Pengfei AU - Zhao P AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, 3rd Section S Renmin Road, 14#, Chengdu, PR China; Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, PR China. FAU - Yuan, Quan AU - Yuan Q AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, 3rd Section S Renmin Road, 14#, Chengdu, PR China; Department of Implantology, West China Hospital of Stomatology, Sichuan University, PR China. FAU - Ji, Ning AU - Ji N AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, 3rd Section S Renmin Road, 14#, Chengdu, PR China. FAU - Ding, Yi AU - Ding Y AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, 3rd Section S Renmin Road, 14#, Chengdu, PR China; Department of Periodontology, West China Hospital of Stomatology, Sichuan University, PR China. FAU - Wang, Qi AU - Wang Q AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, 3rd Section S Renmin Road, 14#, Chengdu, PR China; Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, PR China. Electronic address: wqinno8751@gmail.com. LA - eng PT - Journal Article DEP - 20200516 PL - England TA - Arch Oral Biol JT - Archives of oral biology JID - 0116711 RN - 0 (Inflammasomes) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 9100L32L2N (Metformin) RN - EC 2.7.11.1 (NIMA-Related Kinases) RN - EC 2.7.11.1 (Nek7 protein, mouse) SB - IM MH - Animals MH - *Diabetes Complications MH - *Diabetes Mellitus MH - Inflammasomes MH - *Metformin/pharmacology MH - Mice MH - NIMA-Related Kinases/drug effects MH - NLR Family, Pyrin Domain-Containing 3 Protein MH - *Periodontitis/drug therapy/etiology MH - Pyroptosis OTO - NOTNLM OT - Diabetes mellitus OT - Inflammasome OT - Metformin OT - Periodontitis OT - Pyroptosis OT - lncRNA EDAT- 2020/06/02 06:00 MHDA- 2020/10/30 06:00 CRDT- 2020/06/02 06:00 PHST- 2020/02/25 00:00 [received] PHST- 2020/05/05 00:00 [revised] PHST- 2020/05/06 00:00 [accepted] PHST- 2020/06/02 06:00 [pubmed] PHST- 2020/10/30 06:00 [medline] PHST- 2020/06/02 06:00 [entrez] AID - S0003-9969(20)30141-2 [pii] AID - 10.1016/j.archoralbio.2020.104763 [doi] PST - ppublish SO - Arch Oral Biol. 2020 Aug;116:104763. doi: 10.1016/j.archoralbio.2020.104763. Epub 2020 May 16.