{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:06:38Z","timestamp":1791846398013,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"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":["82170930"],"award-info":[{"award-number":["82170930"]}],"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":["82201025"],"award-info":[{"award-number":["82201025"]}],"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":["81870744"],"award-info":[{"award-number":["81870744"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>This study aimed to evaluate the role of fibulin\u20103 (FBLN3) in macrophage polarization, its mechanism, and its effect on periodontitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted studies on periodontitis using both clinical samples and ligature\u2010induced mouse periodontitis model. The inflammatory state was assessed using microcomputed tomography, hematoxylin and eosin staining, immunohistochemical staining, and immunofluorescence staining. In vitro, bone marrow\u2010derived macrophages, and RAW 264.7 macrophages were treated with lipopolysaccharide (LPS) and interleukin (IL)\u20104 to induce polarization. The role of FBLN3 in macrophage polarization was investigated using overexpression plasmids or siRNAs. Furthermore, local injection of adeno\u2010associated virus was employed to suppress FBLN3 expression in periodontal tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>FBLN3 levels were greater in periodontitis tissues. FBLN3 promoted M1 polarization and suppressed M2 polarization in macrophages. The overexpression of FBLN3 promoted M1 polarization via the EGFR\/PI3K\/AKT signaling pathway, an effect that the epidermal growth factor receptor (EGFR) inhibitor PD153035 reversed. Suppressing FBLN3 expression improved periodontal inflammation and reduced alveolar bone loss in periodontitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>FBLN3 suppression can mitigate periodontitis by decreasing the M1 macrophage ratio. FBLN3 regulates M1 macrophage polarization through the EGFR\/PI3K\/AKT signaling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>Disruption in the collaboration between extracellular matrix (ECM) and immune system is a significant pathology in periodontitis. Macrophages are a crucial part of the immune system and have unique functions, such as polarization. Fibulin\u20103, an ECM protein, may play a vital role in this dynamic interplay. Fibulin\u20103 expression is elevated in periodontitis and is closely related to immune cell function. Inhibiting fibulin\u20103 can alleviate periodontitis by reducing infiltration of immune cells and M1 macrophage ratio. Furthermore, fibulin\u20103 promoted macrophage M1 polarization by activating the PI3K\/AKT signaling pathway through EGFR binding. Our findings offer a clinically relevant rationale for immune response modulation through fibulin\u20103.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.24-0405","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T09:01:07Z","timestamp":1734512467000},"page":"440-454","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inhibition of fibulin\u20103 ameliorates periodontal inflammation through reducing M1 macrophage polarization via EGFR\/PI3K\/AKT pathway"],"prefix":"10.1002","volume":"96","author":[{"given":"Hailin","family":"Mu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology, Wuhan University  Wuhan Hubei 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