{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:21:34Z","timestamp":1790310094871,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T00:00:00Z","timestamp":1755993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T00:00:00Z","timestamp":1755993600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Given the recognized importance of pyruvate kinase M2 isoform (PKM2) in immunometabolism and periodontitis, yet a lack of synthesis on its dual metabolic and non\u2010metabolic functions across key periodontal cell types, this short review aims to explore the central mechanisms by which PKM2 drives sustained inflammation and bone metabolic imbalance. It examines its role as a molecular hub linking \u201cmetabolism\u2010immune\u2010bone destruction\u201d to provide insights into disease mechanisms and targeted therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Subjects and Methods<\/jats:title>\n                    <jats:p>The review integrates recent advances in immunometabolism and periodontitis research. Through comprehensive analysis of PKM2's dual \u201cmetabolic and non\u2010metabolic\u201d roles in macrophage polarization, T\u2010cell subset regulation, neutrophil function, and bone metabolism, its molecular network mediating host immune dysregulation and tissue destruction is revealed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PKM2 activates glycolysis to promote M1 macrophage polarization and enhance pro\u2010inflammatory cytokine release. PKM2 induces T\u2010cell subset imbalance (Th17\/Treg dysregulation), exacerbating inflammatory responses. PKM2 mediates neutrophil oxidative stress damage, amplifying local tissue destruction. PKM2 drives alveolar bone resorption by regulating osteoclast differentiation and osteoblast dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>As a core hub connecting microbial dysbiosis, host metabolic reprogramming, and pathological outcomes, PKM2's dual functional properties offer a novel therapeutic target for periodontitis beyond conventional antimicrobial\/anti\u2010inflammatory strategies. Targeting PKM2 or its downstream metabolic\u2010immune crosstalk may represent a breakthrough for halting disease progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.70075","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T06:24:59Z","timestamp":1756103099000},"page":"56-64","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>PKM2<\/scp>\n                    's Dual Role in Periodontitis: Regulating Inflammation and Bone Metabolism Imbalance"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1474-2107","authenticated-orcid":false,"given":"Han","family":"Gao","sequence":"first","affiliation":[{"name":"Zhuhai Stomatological Hospital  Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.RA118.000718"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190613"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12548"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau3333"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.adaj.2018.04.023"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010023\u201004449\u20100"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155973"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/app15042019"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100757.2012.00457.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10070784"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102866"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3785"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201007667\u20106"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034521990652"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010020\u201002664\u20107"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2014.140403"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201045473\u2010y"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.627328"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413\u2010023\u201000251\u20102"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/idj.12630"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276\u2010024\u201001376\u2010y"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103059"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.111658"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2025.108389"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12950\u2010024\u201000406\u2010w"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2024.106537"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina61010020"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600\u2010051x.2003.00371.x"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12104"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201048615\u20102"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010021\u201000670\u20103"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.12.005"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.60779"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201056615\u20101"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/08923973.2022.2086139"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13651"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.92741"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201040021\u20106"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.75434"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/jleuko\/qiad054"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202301300"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apcsb.2019.12.001"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2023.166795"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43939\u2010024\u201000133\u20102"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201049558\u20104"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010024\u201007227\u2010w"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000001568"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.12360\/CPB202202004"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201092165\u20108"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931\u2010024\u201002926\u20108"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2022.11.009"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010025\u201004301\u2010w"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"1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