Targeting the succinate receptor effectively inhibits periodontitis

被引：20

作者：

Guo, Yuqi ^{[1
]}

Xu, Fangxi ^{[1
]}

Thomas, Scott C. ^{[1
]}

Zhang, Yanli ^{[1
]}

Paul, Bidisha ^{[1
]}

Sakilam, Satish ^{[2
]}

Chae, Sungpil ^{[1
]}

Li, Patty ^{[1
]}

Almeter, Caleb ^{[1
]}

Kamer, Angela R. ^{[3
]}

Arora, Paramjit ^{[2
]}

Graves, Dana T. ^{[4
]}

Saxena, Deepak ^{[1
,5
]}

Li, Xin ^{[1
,5
]}

机构：

[1] NYU, Dept Mol Pathobiol, Coll Dent, New York, NY 10010 USA

[2] NYU, Dept Chem, New York, NY 10003 USA

[3] NYU, Dept Periodontol & Implant Dent, Coll Dent, New York, NY 10010 USA

[4] Univ Penn, Dept Periodont, Sch Dent Med, Philadelphia, PA 19104 USA

[5] NYU, Dept Urol, Grossman Sch Med, New York, NY 10016 USA

来源：

CELL REPORTS | 2022年 / 40卷 / 12期

关键词：

GINGIVAL CREVICULAR FLUID; PORPHYROMONAS-GINGIVALIS; TREPONEMA-DENTICOLA; MICROBIOTA; UPDATE; MODELS; SIGNAL; SALIVA; FLOW;

D O I：

10.1016/j.celrep.2022.111389

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Periodontal disease (PD) is one of the most common inflammatory diseases in humans and is initiated by an oral microbial dysbiosis that stimulates inflammation and bone loss. Here, we report an abnormal elevation of succinate in the subgingival plaque of subjects with severe PD. Succinate activates succinate receptor-1 (SUCNR1) and stimulates inflammation. We detected SUCNR1 expression in the human and mouse periodon-tium and hypothesize that succinate activates SUCNR1 to accelerate periodontitis through the inflammatory response. Administration of exogenous succinate enhanced periodontal disease, whereas SUCNR1 knockout mice were protected from inflammation, oral dysbiosis, and subsequent periodontal bone loss in two different models of periodontitis. Therapeutic studies demonstrated that a SUCNR1 antagonist inhibited inflammatory events and osteoclastogenesis in vitro and reduced periodontal bone loss in vivo. Our study reveals succi-nate's effect on periodontitis pathogenesis and provides a topical treatment for this disease.

引用

页数：24

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