{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:58:02Z","timestamp":1791849482786,"version":"4.3.4"},"reference-count":65,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"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":["82470978"],"award-info":[{"award-number":["82470978"]}],"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":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To investigate the influence and mechanism of exosomes derived from human gingival mesenchymal stem cells (GMSC\u2010Exo) regulating macrophage polarisation through metabolic reprogramming.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Human acute monocytic leukaemia cells (THP\u20101)\u2010derived macrophages were treated with\u00a0GMSC\u2010Exo or <jats:styled-content style=\"fixed-case\">\n<jats:italic>Porphyromonas gingivalis<\/jats:italic>\n<\/jats:styled-content> lipopolysaccharide (<jats:italic>P.g<\/jats:italic>\u2010LPS) in\u00a0vitro. Metabolic inhibitors were used to study the role of metabolic reprogramming in GMSC\u2010Exo\u2010induced polarisation, while the hypoxia\u2010inducible factor\u20101 alpha\u00a0(HIF\u20101\u03b1)\u00a0modulators were employed to explore the HIF\u20101\u03b1 signalling pathway's impact on macrophage metabolic reprogramming. The impact of GMSC\u2010Exo on periodontitis and macrophage metabolism was assessed using a rat model in\u00a0vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vitro experiments confirmed that GMSC\u2010Exo promoted the polarisation of macrophages from pro\u2010inflammatory M1 type (classically activated) to anti\u2010inflammatory M2 type (alternatively activated) by promoting metabolic reprogramming (glycolysis to oxidative phosphorylation). In this process, the activation of the HIF\u20101\u03b1 signalling pathway was inhibited. In\u00a0vivo experiments revealed that GMSC\u2010Exo could regulate the inflammatory microenvironment of periodontal tissue and the metabolic pattern of macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>By inhibiting the activation of HIF\u20101\u03b1 signalling pathway, GMSC\u2010Exo trigger metabolic reprogramming in macrophages, thereby regulating the macrophage transformation from pro\u2010inflammatory M1 phenotype to anti\u2010inflammatory\u00a0M2 phenotype. This change enhances the local inflammatory environment, aiding tissue repair and regeneration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jcpe.14184","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T18:59:08Z","timestamp":1747681148000},"page":"1196-1210","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Exosomes Derived From Human Gingival Mesenchymal Stem Cells Induce Metabolic Reprogramming of Inflammatory Macrophages"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4301-9936","authenticated-orcid":false,"given":"Jialu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Stomatology The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"School of Stomatology Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3810-883X","authenticated-orcid":false,"given":"Yingzhe","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Qingdao Huangdao Central Hospital  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Burn and Plastic Surgery The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Stomatology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Stomatology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Stomatology The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"School of Stomatology Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Stomatology The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"School of Stomatology Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingshu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Stomatology The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"School of Stomatology Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0484-0878","authenticated-orcid":false,"given":"Quanchen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Stomatology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25063562"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22158295"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2014.05.001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2017.04.021"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114279"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.14087"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075\u2010023\u201003185\u20106"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441\u2010023\u201003743\u2010z"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.2002499"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107901"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm\u201020\u20101114"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010023\u201004772\u20106"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41573\u2010020\u201000220\u2010y"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.07.017"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13312"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.01.047"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1990515"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2022.109216"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121439"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110192"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13798"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.09.016"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20082023"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001499\u20100"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.13152"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2017.01.056"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2021.001"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.05.012"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13020\u2010024\u201000933\u2010x"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2023.08.009"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/d2na00762b"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13770\u2010023\u201000525\u20100"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010022\u201000902\u20100"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2020.12.046"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.2147\/ijn.S470419"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2020.08.012"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010024\u201002592\u20104"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.121038"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010025\u201003250\u2010z"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e17167"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101564"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202303584"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2023.05.024"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010022\u201000547\u2010x"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.918747"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.05.011"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.106030"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.111984"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2025.107259"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010021\u201000791\u20109"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.13701\/j.cnki.kqyxyj.2024.07.002"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.10.004"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.14144"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.69533"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40779\u2010022\u201000426\u20108"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.781378"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.61080"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00287"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121484"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.3233\/thc\u2010220092"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.07.008"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107455"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1159\/000542531"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1449411"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00026.2013"}],"container-title":["Journal of Clinical Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcpe.14184","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T01:20:41Z","timestamp":1752542441000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcpe.14184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,19]]},"references-count":65,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/jcpe.14184"],"URL":"https:\/\/doi.org\/10.1111\/jcpe.14184","archive":["Portico"],"relation":{},"ISSN":["0303-6979","1600-051X"],"issn-type":[{"value":"0303-6979","type":"print"},{"value":"1600-051X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,19]]},"assertion":[{"value":"2024-12-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}