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

Frontiers in Cell and Developmental Biology - Tập 9
Qin Chen1,2,3,4,5,6, Xingguang Liu7, Dingyu Wang8, Jisi Zheng1,2,3,4,5,6, Lu Chen1,2,3,4,5,6, Qianyang Xie1,2,3,4,5,6, Xiaohan Liu1,2,3,4,5,6, Sujuan Niu9, Guanlin Qu10, Jianfeng Lan11, Jing Li12, Chi Yang1,2,3,4,5,6, Duohong Zou1,2,3,4,5,6
1College of Stomatology, Shanghai Jiao Tong University
2National Center for Stomatology
3National Clinical Research Center for Oral Diseases
4Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
5Shanghai Key Laboratory of Stomatology
6Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
7National Key Laboratory of Medical Immunology, Navy Military Medical University, Shanghai, China
8State Key Laboratory of Pharmaceutical Biotechnology and Ministry of Education, Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China
9College of Stomatology, Inner Mongolia Medical University, Hohhot, China
10Liaoning Provincial Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, China Medical University, Shenyang, China
11Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, the Affiliated Hospital of Guilin Medical University, Guilin, China
12Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, China

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

Aglietti, 2017, Recent insights into the molecular mechanisms underlying pyroptosis and gasdermin family functions., Trends Immunol., 38, 261, 10.1016/j.it.2017.01.003

Al-Habib, 2019, Dental mesenchymal stem cells: dental pulp stem cells, periodontal ligament stem cells, apical papilla stem cells, and primary teeth stem cells—isolation, characterization, and expansion for tissue engineering., Methods Mol. Biol., 1922, 59, 10.1007/978-1-4939-9012-2_7

2011, Comprehensive periodontal therapy: a statement by the American Academy of Periodontology., J. Periodontol., 82, 943, 10.1902/jop.2011.117001

Aoyama, 2019, Increased heart failure prevalence in patients with a high antibody level against periodontal pathogen., Int. Heart J., 60, 1142, 10.1536/ihj.19-010

Aral, 2020, Inflammasomes and their regulation in periodontal disease: a review., J. Periodontal Res., 55, 473, 10.1111/jre.12733

Bartold, 2017, Standardization of criteria defining periodontal ligament stem cells., J. Dent. Res., 96, 487, 10.1177/0022034517697653

Bhattarai, 2016, Resveratrol prevents alveolar bone loss in an experimental rat model of periodontitis., Acta Biomater., 29, 398, 10.1016/j.actbio.2015.10.031

Caton, 2018, A new classification scheme for periodontal and peri-implant diseases and conditions–Introduction and key changes from the 1999 classification., J. Periodontol., 89, S1, 10.1002/JPER.18-0157

Chen, 2020, Herpesvirus-bacteria synergistic interaction in periodontitis., Periodontology, 2000, 42, 10.1111/prd.12311

Chen, 2016, Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial., Stem Cell Res. Ther., 7, 10.1186/s13287-016-0288-1

Chen, 2016, Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis., Cell Res., 26, 1007, 10.1038/cr.2016.100

Cheng, 2017, Porphyromonas gingivalis-derived lipopolysaccharide combines hypoxia to induce caspase-1 activation in periodontitis., Front. Cell. Infect. Microbiol., 7, 10.3389/fcimb.2017.00474

Ding, 2016, Pore-forming activity and structural autoinhibition of the gasdermin family., Nature, 535, 111, 10.1038/nature18590

Dominy, 2019, Porphyromonas gingivalis in Alzheimer’s disease brains: evidence for disease causation and treatment with small-molecule inhibitors., Sci. Adv., 5, 10.1126/sciadv.aau3333

Fawzy El-Sayed, 2019, The periodontal stem/progenitor cell inflammatory-regenerative cross talk: a new perspective., J. Periodontal Res., 54, 81, 10.1111/jre.12616

García-Hernández, 2019, Upregulation of proteins of the NLRP3 inflammasome in patients with periodontitis and uncontrolled type 2 diabetes., Oral Diseases, 25, 596, 10.1111/odi.13003

Gomes, 2016, Inflammatory cytokines interleukin-1β and tumour necrosis factor-α-novel biomarkers for the detection of periodontal diseases: a literature review., J. Oral Maxillofac. Res., 7, 10.5037/jomr.2016.7202

Hajishengallis, 2015, Periodontitis: from microbial immune subversion to systemic inflammation., Nat. Rev. Immunol., 15, 30, 10.1038/nri3785

Hasan, 2014, A clinical guide to periodontology: pathology of periodontal disease., Br. Dent. J., 216, 457, 10.1038/sj.bdj.2014.299

He, 2015, Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion., Cell Res., 25, 1285, 10.1038/cr.2015.139

Hienz, 2015, Mechanisms of bone resorption in periodontitis., J. Immunol. Res., 2015, 10.1155/2015/615486

Jia, 2020, Cyclic compression emerged dual effects on the osteogenic and osteoclastic status of LPS-induced inflammatory human periodontal ligament cells according to loading force., BMC Oral Health, 20, 10.1186/s12903-019-0987-y

Jun, 2018, Caspase-4 activation by a bacterial surface protein is mediated by cathepsin G in human gingival fibroblasts., Cell Death Differ., 25, 380, 10.1038/cdd.2017.167

Kayagaki, 2015, Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling., Nature, 526, 666, 10.1038/nature15541

Kesavardhana, 2020, Caspases in cell death, inflammation, and pyroptosis., Annu. Rev. Immunol., 38, 567, 10.1146/annurev-immunol-073119-095439

Kinane, 2017, Periodontal diseases., Nat. Rev. Dis. Primers, 3, 1, 10.1038/nrdp.2017.38

Kuula, 2009, Local and systemic responses in matrix metalloproteinase 8-deficient mice during Porphyromonas gingivalis-induced periodontitis., Infect. Immunity, 77, 850, 10.1128/iai.00873-08

Li, 2017, High-dose PMA with RANKL and MCSF induces THP-1 cell differentiation into human functional osteoclasts in vitro., Mol. Med. Rep., 16, 8380, 10.3892/mmr.2017.7625

Liu, 2016, Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores., Nature, 535, 153, 10.1038/nature18629

Liu, 2008, Periodontal ligament stem cell−mediated treatment for periodontitis in miniature swine., Stem Cells, 26, 1065, 10.1634/stemcells.2007-0734

Ma, 2020, Gasdermin D in macrophages restrains colitis by controlling cGAS-mediated inflammation., Sci. Adv., 6, 10.1126/sciadv.aaz6717

Man, 2017, Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases., Immunol. Rev., 277, 61, 10.1111/imr.12534

Mao, 2016, Double-edged-sword effect of IL-1 β on the osteogenesis of periodontal ligament stem cells via crosstalk between the NF-κ B, MAPK and BMP/Smad signaling pathways., Cell Death Dis., 7, 10.1038/cddis.2016.204

Marchesan, 2018, An experimental murine model to study periodontitis., Nat. Protoc., 13, 2247, 10.1038/s41596-018-0035-4

Monteleone, 2018, Interleukin-1β maturation triggers its relocation to the plasma membrane for gasdermin-D-dependent and-independent secretion., Cell Rep., 24, 1425, 10.1016/j.celrep.2018.07.027

Mrozik, 2013, Regeneration of periodontal tissues using allogeneic periodontal ligament stem cells in an ovine model., Regenerative Med., 8, 711, 10.2217/rme.13.66

Okondo, 2017, DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis., Nat. Chem. Biol., 13, 46, 10.1038/nchembio.2229

Papathanasiou, 2020, IL-1 superfamily members and periodontal diseases., J. Dent. Res., 99, 1425, 10.1177/0022034520945209

Pihlstrom, 2005, Periodontal diseases., Lancet, 366, 1809, 10.1016/S0140-6736(05)67728-8

Polak, 2018, An update on the evidence for pathogenic mechanisms that may link periodontitis and diabetes., J. Clin. Periodontol., 45, 150, 10.1111/jcpe.12803

Rathinam, 2019, Innate immunity to intracellular LPS., Nat. Immunol., 20, 527, 10.1038/s41590-019-0368-3

Ren, 2019, Osteoprotegerin reduces osteoclast resorption activity without affecting osteogenesis on nanoparticulate mineralized collagen scaffolds., Sci. Adv., 5, 10.1126/sciadv.aaw4991

Rocha, 2020, Relevance of Caspase-1 and Nlrp3 inflammasome on inflammatory bone resorption in A murine model of periodontitis., Sci. Rep., 10, 10.1038/s41598-020-64685-y

Santana, 2016, The ligature-induced periodontitis model: literature overview and description of the technique, Periodontal Disease: Diagnosis, Management Options and Clinical Features, 23

Sanz, 2012, Nonsurgical treatment of periodontitis., J. Evid. Based Dent. Pract., 12, 76, 10.1016/S1532-3382(12)70019-2

Seo, 2004, Investigation of multipotent postnatal stem cells from human periodontal ligament., Lancet, 364, 149, 10.1016/s0140-6736(04)16627-0

Shi, 2015, Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death., Nature, 526, 660, 10.1038/nature15514

Tassi, 2017, Efficacy of stem cells on periodontal regeneration: systematic review of pre-clinical studies., J. Periodontal Res., 52, 793, 10.1111/jre.12455

Trubiani, 2019, Periodontal ligament stem cells: current knowledge and future perspectives., Stem Cells Dev., 28, 995, 10.1089/scd.2019.0025

Vandana, 2015, Autologous stem cell application in periodontal regeneration technique (SAI-PRT) using PDLSCs directly from an extracted tooth⋅an insight., Int. J. Stem Cells, 8, 10.15283/ijsc.2015.8.2.235

Wang, 2020, Magnesium protects against sepsis by blocking gasdermin D N-terminal-induced pyroptosis., Cell Death Differ., 27, 466, 10.1038/s41418-019-0366-x

Wang, 2017, NLRP3 inflammasome activation in mesenchymal stem cells inhibits osteogenic differentiation and enhances adipogenic differentiation., Biochem. Biophys. Res. Commun., 484, 871, 10.1016/j.bbrc.2017.02.007

Xia, 2020, Mechanism and regulation of gasdermin-mediated cell death., Cold Spring Harb. Perspect. Biol., 12, 10.1101/cshperspect.a036400

Yamaguchi, 2017, Regulation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated periodontal disease., Inflamm. Res., 66, 59, 10.1007/s00011-016-0992-4

Zhuang, 2019, Gasdermin-d played a critical role in the cyclic stretch–induced inflammatory reaction in human periodontal ligament cells., Inflammation, 42, 548, 10.1007/s10753-018-0912-6

Thông tin
Thông tin xuất bản

Frontiers in Cell and Developmental Biology

Tập 9

Thông tin tác giả