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Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis

Periodontitis is an immune inflammatory disease that leads to progressive destruction of bone and connective tissue, accompanied by the dysfunction and even loss of periodontal ligament stem cells (PDLSCs). Pyroptosis mediated by gasdermin-D (GSDMD) participates in the pathogenesis of inflammatory d...

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Autores principales: Chen, Qin, Liu, Xingguang, Wang, Dingyu, Zheng, Jisi, Chen, Lu, Xie, Qianyang, Liu, Xiaohan, Niu, Sujuan, Qu, Guanlin, Lan, Jianfeng, Li, Jing, Yang, Chi, Zou, Duohong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049442/
https://www.ncbi.nlm.nih.gov/pubmed/33869229
http://dx.doi.org/10.3389/fcell.2021.663037
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author Chen, Qin
Liu, Xingguang
Wang, Dingyu
Zheng, Jisi
Chen, Lu
Xie, Qianyang
Liu, Xiaohan
Niu, Sujuan
Qu, Guanlin
Lan, Jianfeng
Li, Jing
Yang, Chi
Zou, Duohong
author_facet Chen, Qin
Liu, Xingguang
Wang, Dingyu
Zheng, Jisi
Chen, Lu
Xie, Qianyang
Liu, Xiaohan
Niu, Sujuan
Qu, Guanlin
Lan, Jianfeng
Li, Jing
Yang, Chi
Zou, Duohong
author_sort Chen, Qin
collection PubMed
description Periodontitis is an immune inflammatory disease that leads to progressive destruction of bone and connective tissue, accompanied by the dysfunction and even loss of periodontal ligament stem cells (PDLSCs). Pyroptosis mediated by gasdermin-D (GSDMD) participates in the pathogenesis of inflammatory diseases. However, whether pyroptosis mediates PDLSC loss, and inflammation triggered by pyroptosis is involved in the pathological progression of periodontitis remain unclear. Here, we found that PDLSCs suffered GSDMD-dependent pyroptosis to release interleukin-1β (IL-1β) during human periodontitis. Importantly, the increased IL-1β level in gingival crevicular fluid was significantly correlated with periodontitis severity. The caspase-4/GSDMD-mediated pyroptosis caused by periodontal bacteria and cytoplasmic lipopolysaccharide (LPS) dominantly contributed to PDLSC loss. By releasing IL-1β into the tissue microenvironment, pyroptotic PDLSCs inhibited osteoblastogenesis and promoted osteoclastogenesis, which exacerbated the pathological damage of periodontitis. Pharmacological inhibition of caspase-4 or IL-1β antibody blockade in a rat periodontitis model lead to the significantly reduced loss of alveolar bone and periodontal ligament damage. Furthermore, Gsdmd deficiency alleviated periodontal inflammation and bone loss in mouse experimental periodontitis. These findings indicate that GSDMD-driven PDLSC pyroptosis and loss plays a pivotal role in the pathogenesis of periodontitis by increasing IL-1β release, enhancing inflammation, and promoting osteoclastogenesis.
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spelling pubmed-80494422021-04-16 Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis Chen, Qin Liu, Xingguang Wang, Dingyu Zheng, Jisi Chen, Lu Xie, Qianyang Liu, Xiaohan Niu, Sujuan Qu, Guanlin Lan, Jianfeng Li, Jing Yang, Chi Zou, Duohong Front Cell Dev Biol Cell and Developmental Biology Periodontitis is an immune inflammatory disease that leads to progressive destruction of bone and connective tissue, accompanied by the dysfunction and even loss of periodontal ligament stem cells (PDLSCs). Pyroptosis mediated by gasdermin-D (GSDMD) participates in the pathogenesis of inflammatory diseases. However, whether pyroptosis mediates PDLSC loss, and inflammation triggered by pyroptosis is involved in the pathological progression of periodontitis remain unclear. Here, we found that PDLSCs suffered GSDMD-dependent pyroptosis to release interleukin-1β (IL-1β) during human periodontitis. Importantly, the increased IL-1β level in gingival crevicular fluid was significantly correlated with periodontitis severity. The caspase-4/GSDMD-mediated pyroptosis caused by periodontal bacteria and cytoplasmic lipopolysaccharide (LPS) dominantly contributed to PDLSC loss. By releasing IL-1β into the tissue microenvironment, pyroptotic PDLSCs inhibited osteoblastogenesis and promoted osteoclastogenesis, which exacerbated the pathological damage of periodontitis. Pharmacological inhibition of caspase-4 or IL-1β antibody blockade in a rat periodontitis model lead to the significantly reduced loss of alveolar bone and periodontal ligament damage. Furthermore, Gsdmd deficiency alleviated periodontal inflammation and bone loss in mouse experimental periodontitis. These findings indicate that GSDMD-driven PDLSC pyroptosis and loss plays a pivotal role in the pathogenesis of periodontitis by increasing IL-1β release, enhancing inflammation, and promoting osteoclastogenesis. Frontiers Media S.A. 2021-04-01 /pmc/articles/PMC8049442/ /pubmed/33869229 http://dx.doi.org/10.3389/fcell.2021.663037 Text en Copyright © 2021 Chen, Liu, Wang, Zheng, Chen, Xie, Liu, Niu, Qu, Lan, Li, Yang and Zou. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Chen, Qin
Liu, Xingguang
Wang, Dingyu
Zheng, Jisi
Chen, Lu
Xie, Qianyang
Liu, Xiaohan
Niu, Sujuan
Qu, Guanlin
Lan, Jianfeng
Li, Jing
Yang, Chi
Zou, Duohong
Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis
title Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis
title_full Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis
title_fullStr Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis
title_full_unstemmed Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis
title_short Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis
title_sort periodontal inflammation-triggered by periodontal ligament stem cell pyroptosis exacerbates periodontitis
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049442/
https://www.ncbi.nlm.nih.gov/pubmed/33869229
http://dx.doi.org/10.3389/fcell.2021.663037
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