{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:30:57Z","timestamp":1786361457476,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32471176"],"award-info":[{"award-number":["32471176"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82430031"],"award-info":[{"award-number":["82430031"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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\u2010coupled receptors (GPCRs) enhance insulin secretion and attenuate inflammation. We hypothesized that GPCR regulators may contribute to crosstalk between systemic metabolic abnormalities and periodontal immunopathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using db\/db mice with ligature\u2010induced periodontitis, we performed multi\u2010tissue transcriptomics of gingiva, colon, and small intestine combined with weighted gene co\u2010expression network analysis (WGCNA) to identify GPCR\u2010related candidates. The selective G protein\u2010coupled receptor 120 (GPR120) agonist TUG\u2010891 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\u2010 and NLRP3\u2010related responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>WGCNA identified GPR120 as a shared GPCR\u2010related candidate across three tissues in diabetic periodontitis, with upregulation confirmed in gingiva. TUG\u2010891 partially alleviated hyperglycemia, dyslipidemia, and alveolar bone loss. GPR120 activation reduced NET\u2010associated signals in vivo and in vitro, downregulated calcium\/potassium signaling (upstream NLRP3 activators), and decreased LPS\/glucose\u2010induced upregulation of NLRP3 and ASC in neutrophils. The NLRP3 inhibitor MCC950 phenocopied, while the NLRP3 activator nigericin reversed, the NET\u2010associated changes of TUG\u2010891.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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\u2010related responses, and NET\u2010associated inflammation may hold therapeutic potential for this common diabetic complication.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.70191","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T10:53:52Z","timestamp":1786359232000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological activation of GPR120 ameliorates diabetic periodontitis in mouse models through suppression of NET\u2010associated responses"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1126-1724","authenticated-orcid":false,"given":"Chao","family":"Jiang","sequence":"first","affiliation":[{"name":"Stomatology 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Shi","sequence":"additional","affiliation":[{"name":"Stomatology 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biwen","family":"Yao","sequence":"additional","affiliation":[{"name":"Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Diseases Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kedie","family":"Zhang","sequence":"additional","affiliation":[{"name":"School\/Hospital of Stomatology Zhejiang Chinese Medical University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Yin","sequence":"additional","affiliation":[{"name":"Stomatology 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyi","family":"Zhu","sequence":"additional","affiliation":[{"name":"School\/Hospital of Stomatology Zhejiang Chinese Medical University  Hangzhou Zhejiang 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