{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:49:12Z","timestamp":1791866952337,"version":"4.3.4"},"reference-count":31,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"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>Periodontitis is a chronic inflammatory disease driven by dysregulated immune responses and is closely associated with macrophage polarization. N6\u2010methyladenosine (m6A) methylation represents the most prevalent RNA modification; however, its role in periodontitis remains unclear. This study aimed to investigate the mechanism by which m6A modification regulates macrophage polarization during the progression of periodontitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A periodontitis mouse model was established by ligature induction. RAW264.7 macrophages were treated with\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      \u2010derived lipopolysaccharide (LPS) to simulate inflammatory conditions in vitro. Micro\u2010computed tomography (micro\u2010CT), hematoxylin\u2010eosin and immunohistochemical staining, quantitative real\u2010time polymerase chain reaction (qPCR), immunofluorescence staining, methylated RNA immunoprecipitation (MeRIP), and luciferase reporter assays were used to evaluate alveolar bone loss, macrophage phenotypes, and m6A\u2010dependent regulatory mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Methyltransferase\u2010like 3 (METTL3) expression was significantly upregulated in periodontitis tissues and in LPS\u2010stimulated macrophages. Knockdown of METTL3 attenuated alveolar bone resorption, reduced pro\u2011inflammatory M1 markers (tumor necrosis factor\u2010alpha [TNF\u2010\u03b1], interleukin\u20106 [IL\u20106]), and increased M2 markers (IL\u201010, arginase\u20101 [Arg\u20101]) in mice. In LPS\u2010treated RAW264.7 cells, METTL3 knockdown suppressed M1 polarization markers (CD86, TNF\u2010\u03b1, IL\u20101\u03b2) and enhanced M2 markers (CD206, transforming growth factor\u2010beta [TGF\u2010\u03b2]). Mechanistically, METTL3 stabilized LPS\u2010binding protein (LBP) mRNA via m6A modification, and overexpression of LBP reversed the METTL3 knockdown\u2010mediated suppression of M1 polarization. RNA immunoprecipitation (RIP) and dual\u2010luciferase assays identified YTHDF1 as the m6A reader responsible for recognizing LBP mRNA. These results indicate that METTL3 promotes periodontitis by enhancing LBP mRNA stability through m6A methylation, thereby driving M1 macrophage polarization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identifies the METTL3\u2010LBP\u2010YTHDF1 axis as a key regulator of macrophage\u2010driven inflammation in periodontitis, providing new potential therapeutic targets for modulating immune responses in periodontal disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain language summary<\/jats:title>\n                    <jats:p>Periodontitis is a common chronic inflammatory disease that damages gum tissue and tooth\u2010supporting bones and can lead to tooth loss if untreated. Immune cells called macrophages play a key role here\u2014when they become \u201cpro\u2010inflammatory\u201d (promoting inflammation), the disease worsens. We studied a molecule called methyltransferase\u2010like 3 (METTL3), which is more abundant in periodontitis tissues and inflamed cells. Using mouse models and lab\u2010grown cells, we found that reducing METTL3 levels eased inflammation, protected tooth\u2010supporting bones, and shifted macrophages from pro\u2010inflammatory to anti\u2010inflammatory (a type that helps repair tissue). This happens because METTL3 causes a common chemical change in RNA to stabilize another molecule, lipopolysaccharide\u2010binding protein (LBP), with the help of a protein called YTHDF1. Our findings show that the METTL3\u2010LBP\u2010YTHDF1 pathway drives periodontitis by boosting harmful inflammation, offering a new target for developing treatments to regulate immune responses and improve oral health.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.70195","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:35:59Z","timestamp":1791866159000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["METTL3\u2010mediated m6A methylation of lipopolysaccharide\u2010binding protein exacerbates periodontitis by promoting M1 macrophage polarization"],"prefix":"10.1002","author":[{"given":"Hongwei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthodontics Hebei Eye Hospital, Hebei Provincial Clinical Research Center for Eye Diseases  Xingtai Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huina","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Xingtai People's Hospital  Xingtai Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthodontics Shijiazhuang Second Hospital  Shijiazhuang Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiandong","family":"Ban","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine Hebei Eye Hospital, Hebei Provincial Clinical Research Center for Eye Diseases  Xingtai Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine Hebei Eye Hospital, Hebei Provincial Clinical Research Center for Eye Diseases  Xingtai Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Qiao","sequence":"additional","affiliation":[{"name":"School and Hospital of Stomatology Hebei Medical University  Shijiazhuang Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23095142"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13639"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12337"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13807"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12451"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010020\u201000488\u20106"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.763334"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdsr.2022.10.002"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2024.2427234"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345241235616"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010030\u201096881\u20106_10"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.3c02619"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010020\u201000450\u2010x"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab378"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010024\u201001628\u20108"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2024.111572"},{"key":"e_1_2_11_18_1","doi-asserted-by":"crossref","unstructured":"ZhouX YangX HuangS et\u00a0al.Inhibition of METTL3 alleviates NLRP3 inflammasome activation via increasing ubiquitination of NEK7. 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