{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T18:41:42Z","timestamp":1788633702809,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T00:00:00Z","timestamp":1756598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071084"],"award-info":[{"award-number":["82071084"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Clinic Periodontology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"ABSTRACT<\/jats:title>\n \n Aim<\/jats:title>\n \n This study investigates the association between periodontitis and anxiety, focusing on the role of the chemokine\n CCL2<\/jats:styled-content>\n in mediating this relationship.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n \n This study comprises an analytical cross\u2010sectional study and a preclinical in\u00a0vivo study. In the analytical cross\u2010sectional study, anxiety levels were assessed in individuals with periodontitis and healthy controls using the Hamilton Anxiety Rating Scale (\n HAMA<\/jats:styled-content>\n ). Blood and periodontal tissue samples were analysed for\n CCL2<\/jats:styled-content>\n levels via\n ELISA<\/jats:styled-content>\n and monocyte counts via flow cytometry. In the preclinical in\u00a0vivo study, a mouse model of ligature\u2010induced periodontitis was established. Anxiety\u2010like behaviours were evaluated using the Open Field Test and Elevated Plus Maze. Blood as well as periodontal and brain tissues were collected to measure\n CCL2<\/jats:styled-content>\n levels and monocyte\/macrophage infiltration through\n ELISA<\/jats:styled-content>\n and flow cytometry. Tight junction proteins in periodontal tissues and brain microvessels were analysed via Western blotting and immunofluorescence. Blood\u2013brain barrier (\n BBB)<\/jats:styled-content>\n permeability was assessed using Evans Blue extravasation. A\n CCL2<\/jats:styled-content>\n \u2010neutralising antibody was administered to assess its effects on anxiety and periodontal pathology.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In the analytical cross\u2010sectional study (50 individuals with periodontitis and 50 healthy controls), individuals with periodontitis showed higher anxiety levels, correlating with elevated\n CCL2<\/jats:styled-content>\n levels in blood (56.84 [15.87] pg\/\n mL<\/jats:styled-content>\n vs. 19.28 [7.47] pg\/\n mL<\/jats:styled-content>\n in controls,\n p<\/jats:italic>\n \u2009<\u20090.0001) and periodontal tissues (67.37 [23.10] pg\/\n mL<\/jats:styled-content>\n vs. 22.77 [10.21] pg\/\n mL<\/jats:styled-content>\n in controls,\n p<\/jats:italic>\n \u2009<\u20090.0001), as well as increased monocyte counts (\n CD14<\/jats:styled-content>\n +<\/jats:sup>\n monocytes in blood: 8.08 [3.01]% vs. 5.28 [1.84]% in controls,\n p<\/jats:italic>\n \u2009<\u20090.01). In the preclinical in\u00a0vivo study (total\n n<\/jats:italic>\n \u2009=\u200980 mice, with\n n<\/jats:italic>\n \u2009=\u20098 per group in analyses), periodontal inflammation increased\n CCL2<\/jats:styled-content>\n expression in periodontal tissues (125.80 [55.10] pg\/\n mL<\/jats:styled-content>\n vs. 25.13 [4.89] pg\/\n mL<\/jats:styled-content>\n in controls,\n p<\/jats:italic>\n \u2009<\u20090.001) and blood (111.10 [47.80] pg\/\n mL<\/jats:styled-content>\n vs. 22.21 [5.39] pg\/\n mL<\/jats:styled-content>\n in controls,\n p<\/jats:italic>\n \u2009<\u20090.001), enhanced monocyte\/macrophage infiltration into periodontal tissues (7.75 [1.96]% vs. 4.82 [0.82]% in controls,\n p<\/jats:italic>\n \u2009<\u20090.01) and brain (2.78 [0.91]% vs. 1.38 [0.47]% in controls,\n p<\/jats:italic>\n \u2009<\u20090.01), disrupted the integrity of periodontal tight junction and blood\u2013brain barrier and increased anxiety\u2010like behaviours. Administration of\n CCL2<\/jats:styled-content>\n \u2010neutralising antibody reduced anxiety\u2010like behaviours, attenuated alveolar bone loss and local inflammation and decreased monocyte\/macrophage infiltration and barrier integrity disruption.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The study identifies the association between periodontitis and anxiety, with the\n CCL2<\/jats:styled-content>\n \u2010mediated inflammatory pathogenesis as an underlying mechanism.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jcpe.70020","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T01:29:50Z","timestamp":1756690190000},"page":"1813-1825","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["CCL2<\/scp>\n \u2010Driven Inflammation Links Periodontitis to Anxiety"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1362-4309","authenticated-orcid":false,"given":"Li","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Stomatology Eighth Medical Center of Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1500-1757","authenticated-orcid":false,"given":"Zhen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Stomatology Eighth Medical Center of Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Stomatology Eighth Medical Center of Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Stomatology Eighth Medical Center of Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Stomatology Eighth Medical Center of Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Stomatology Eighth Medical Center of Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010Feng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Beijing Children's Hospital, Capital Medical University, National Center for Children's Health Beijing 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