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Updated: Aug 11, 2026
Induction of Periodontitis via a Combination of Ligature and Lipopolysaccharide Injection in a Rat Model
Published on: February 17, 2023
Pharmacological activation of GPR120 ameliorates diabetic periodontitis in mouse models through suppression of
Chao Jiang1, Yilin Shi1, Biwen Yao2
1Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Zhejiang Key Laboratory of Oral Biomedical, Hangzhou, Zhejiang, China.
Background:
Epidemiological studies show periodontitis and type 2 diabetes share a bidirectional aggravating relationship, yet the molecular mechanisms linking systemic metabolic dysregulation to local periodontal destruction remain unclear, and effective therapies for this comorbidity are lacking. Certain G protein-coupled receptors (GPCRs) enhance insulin secretion and attenuate inflammation. We hypothesized that GPCR regulators may contribute to crosstalk between systemic metabolic abnormalities and periodontal immunopathology.
Methods:
Using db/db mice with ligature-induced periodontitis, we performed multi-tissue transcriptomics of gingiva, colon, and small intestine combined with weighted gene co-expression network analysis (WGCNA) to identify GPCR-related candidates. The selective G protein-coupled receptor 120 (GPR120) agonist TUG-891 was administered to evaluate therapeutic effects on metabolic parameters and alveolar bone loss. In vivo and in vitro experiments, including gingival tissue immunofluorescence, PicoGreen dsDNA quantification, and western blotting were used to assess NET- and NLRP3-related responses.
Results:
WGCNA identified GPR120 as a shared GPCR-related candidate across three tissues in diabetic periodontitis, with upregulation confirmed in gingiva. TUG-891 partially alleviated hyperglycemia, dyslipidemia, and alveolar bone loss. GPR120 activation reduced NET-associated signals in vivo and in vitro, downregulated calcium/potassium signaling (upstream NLRP3 activators), and decreased LPS/glucose-induced upregulation of NLRP3 and ASC in neutrophils. The NLRP3 inhibitor MCC950 phenocopied, while the NLRP3 activator nigericin reversed, the NET-associated changes of TUG-891.
Conclusions:
This study identifies GPR120 as a factor associated with metabolic stress and periodontal destruction in diabetic periodontitis, and suggests that the signaling involving GPR120, NLRP3-related responses, and NET-associated inflammation may hold therapeutic potential for this common diabetic complication.
