{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:02:30Z","timestamp":1790380950966,"version":"4.1.0"},"reference-count":81,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301079"],"award-info":[{"award-number":["82301079"]}],"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":["82571070"],"award-info":[{"award-number":["82571070"]}],"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":["82370957"],"award-info":[{"award-number":["82370957"]}],"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":["82571089"],"award-info":[{"award-number":["82571089"]}],"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":["82401186"],"award-info":[{"award-number":["82401186"]}],"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":["82401138"],"award-info":[{"award-number":["82401138"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017596","name":"Natural Science Basic Research Program of Shaanxi Province","doi-asserted-by":"publisher","award":["2024JC\u2010JCQN\u201073"],"award-info":[{"award-number":["2024JC\u2010JCQN\u201073"]}],"id":[{"id":"10.13039\/501100017596","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"abstract":"ABSTRACT<\/jats:title>\n \n \n P. gingivalis<\/jats:italic>\n <\/jats:styled-content>\n , a keystone periodontal pathogen in periodontitis, is recognized for its capacity to evade host immune clearance. Its intracellular survival leads to both local and systemic infection, thereby increasing the risk of periodontitis and its associated systemic diseases. However, macrophages have limited capacity to clear\n \n P. gingivalis<\/jats:italic>\n <\/jats:styled-content>\n , which contributes to disease establishment and progression. Our findings confirmed\n \n P. gingivalis<\/jats:italic>\n <\/jats:styled-content>\n presence in periodontitis tissue, with intracellular\n \n P. gingivalis<\/jats:italic>\n <\/jats:styled-content>\n mainly located in macrophages. However,\n \n P. gingivalis<\/jats:italic>\n <\/jats:styled-content>\n cannot be completely cleared by macrophages and enters the blood circulation through damaged periodontal tissue, leading to systemic infection. Transcriptomic analysis identified mitochondrial calcium uniporter (MCU) as a potential key molecule associated with\n \n P. gingivalis<\/jats:italic>\n <\/jats:styled-content>\n immune evasion in macrophages. In\u00a0vitro functional analyses further confirmed that\n \n P. gingivalis<\/jats:italic>\n <\/jats:styled-content>\n infection increased MCU expression and led to both cytosolic and mitochondrial calcium overload, thereby impairing intracellular\n \n P. gingivalis<\/jats:italic>\n <\/jats:styled-content>\n clearance in macrophages. Notably, as a natural calcium antagonist, magnesium could inhibit the MCU pathway, reverse calcium overload, and enhance the macrophage\u2010mediated\n \n P. gingivalis<\/jats:italic>\n <\/jats:styled-content>\n clearance. Local administration of magnesium\u2010containing alginate methacryloyl (AlgMA) hydrogel significantly reduced both local and systemic\n \n P. gingivalis<\/jats:italic>\n <\/jats:styled-content>\n infection, relieved inflammation, and alleviated periodontal tissue destruction. Collectively, our findings identify MCU\u2010mediated calcium overload as a previously unrecognized mechanism by which\n \n P. gingivalis<\/jats:italic>\n <\/jats:styled-content>\n evades macrophage immune clearance. Moreover, magnesium\u2010mediated restoration of Ca\n 2+<\/jats:sup>\n homeostasis offers a promising host\u2010directed immunomodulatory therapy for periodontitis and other infectious diseases.\n <\/jats:p>","DOI":"10.1111\/cpr.70282","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:46:52Z","timestamp":1790380012000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Magnesium Enhances Immune Clearance of\n \n P. gingivalis<\/i>\n <\/scp>\n in Macrophages by Suppressing\n MCU<\/scp>\n \u2010Mediated Mitochondrial Calcium Overload"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2754-7423","authenticated-orcid":false,"given":"Dao\u2010Kun","family":"Deng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi China"},{"name":"Military Medical Innovation Center Fourth Military Medical University Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9470-7495","authenticated-orcid":false,"given":"Meng\u2010Jie","family":"Su","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi China"},{"name":"Military Medical Innovation Center Fourth Military Medical University Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3989-5729","authenticated-orcid":false,"given":"Min\u2010Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi China"},{"name":"Military Medical Innovation Center Fourth Military Medical University Xi'an Shaanxi China"},{"name":"Department of Periodontal and Oral Mucosa Changsha Stomatological Hospital Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5553-0282","authenticated-orcid":false,"given":"Yu\u2010Jie","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi China"},{"name":"Military Medical Innovation Center Fourth Military Medical University Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3385-0573","authenticated-orcid":false,"given":"Wenyao","family":"Kongling","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology, Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8361-2194","authenticated-orcid":false,"given":"Hong\u2010Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi China"},{"name":"Military Medical Innovation Center Fourth Military Medical University Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8958-9186","authenticated-orcid":false,"given":"Mei","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi China"},{"name":"Military Medical Innovation Center Fourth Military Medical University Xi'an Shaanxi 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Angiography Patients","volume":"31","author":"Zheng X.","year":"2025","journal-title":"Medical Science Monitor"},{"issue":"4","key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1177\/00220345241303141","article-title":"Porphyromonas gingivalis\n Induces Disturbance of Kynurenine Metabolism Through the Gut\u2010Brain Axis: Implications for Alzheimer's Disease","volume":"104","author":"Zhu H.","year":"2025","journal-title":"Journal of Dental Research"},{"issue":"1","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41368-025-00397-1","article-title":"Periodontitis Pathogen \n Porphyromonas gingivalis\n Promotes Chronic Obstructive Pulmonary Disease via Affecting Neutrophils Chemotaxis and Function","volume":"18","author":"Zhang L.","year":"2026","journal-title":"International Journal of Oral Science"},{"issue":"47","key":"e_1_2_10_16_1","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2405534121","article-title":"CD47 and Thrombospondin\u20101 Contribute to Immune Evasion by \n Porphyromonas gingivalis","volume":"121","author":"Angabo S.","year":"2024","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"1","key":"e_1_2_10_17_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1012821","article-title":"Gingipains Protect \n Porphyromonas gingivalis\n From Macrophage\u2010Mediated Phagocytic Clearance","volume":"21","author":"Widziolek M.","year":"2025","journal-title":"PLoS Pathogens"},{"issue":"5","key":"e_1_2_10_18_1","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1177\/00220345221146097","article-title":"Porphyromonas gingivalis\n Evades Immune Clearance by Regulating Lysosome Efflux","volume":"102","author":"Liu M.","year":"2023","journal-title":"Journal of Dental Research"},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.archoralbio.2022.105467","article-title":"Neutrophil Extracellular Traps Induced by \n Porphyromonas gingivalis\n Lipopolysaccharide Modulate Inflammatory Responses via a Ca2+\u2212Dependent Pathway","volume":"141","author":"Chen J. L.","year":"2022","journal-title":"Archives of Oral Biology"},{"issue":"45","key":"e_1_2_10_20_1","doi-asserted-by":"crossref","first-page":"16684","DOI":"10.1074\/jbc.RA119.009133","article-title":"The Myotubularin MTMR4 Regulates Phagosomal Phosphatidylinositol 3\u2010Phosphate Turnover and Phagocytosis","volume":"294","author":"Sheffield D. A.","year":"2019","journal-title":"Journal of Biological Chemistry"},{"issue":"1","key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1189\/jlb.0110028","article-title":"The Role of Calcium Signaling in Phagocytosis","volume":"88","author":"Nunes P.","year":"2010","journal-title":"Journal of Leukocyte Biology"},{"issue":"3","key":"e_1_2_10_22_1","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1021\/acsabm.0c00968","article-title":"Influenza A Viruses Enter Host Cells via Extracellular ca(2+) Influx\u2010Involved Clathrin\u2010Mediated Endocytosis","volume":"4","author":"Bao M. 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C.","year":"2021","journal-title":"Scientific Reports"},{"issue":"1","key":"e_1_2_10_26_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/s41392-020-0155-5","article-title":"MCU\u2010Induced Mitochondrial Calcium Uptake Promotes Mitochondrial Biogenesis and Colorectal Cancer Growth","volume":"5","author":"Liu Y.","year":"2020","journal-title":"Signal Transduction and Targeted Therapy"},{"issue":"10","key":"e_1_2_10_27_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms27104317","article-title":"Mitochondrial Calcium Overload Drives mtDNA\u2010cGAS\u2010STING Activation via VDAC1 and MCU Upregulation in Periodontitis","volume":"27","author":"Cheng X.","year":"2026","journal-title":"International Journal of Molecular Sciences"},{"issue":"15","key":"e_1_2_10_28_1","doi-asserted-by":"crossref","DOI":"10.1002\/adhm.202203106","article-title":"Mitochondrial Calcium Ion Nanogluttons Alleviate Periodontitis via Controlling mPTPs","volume":"12","author":"He P.","year":"2023","journal-title":"Advanced Healthcare Materials"},{"issue":"6","key":"e_1_2_10_29_1","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1111\/jre.12915","article-title":"Porphyromonas gingivalis\n Survival Skills: Immune Evasion","volume":"56","author":"Zheng S.","year":"2021","journal-title":"Journal of Periodontal Research"},{"issue":"1","key":"e_1_2_10_30_1","first-page":"261","article-title":"The Role of Mg2+ in Immune Cells","volume":"55","author":"Brandao K.","year":"2012","journal-title":"Immunology Research"},{"issue":"7357","key":"e_1_2_10_31_1","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/475462a","article-title":"Magnesium in a Signalling Role","volume":"475","author":"Wu N.","year":"2011","journal-title":"Nature"},{"issue":"5","key":"e_1_2_10_32_1","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics15051419","article-title":"Postbiotic Metabolite of Lactiplantibacillus Plantarum PD18 Against Periodontal Pathogens and Their Virulence Markers in Biofilm Formation","volume":"15","author":"Butrungrod W.","year":"2023","journal-title":"Pharmaceutics"},{"issue":"10","key":"e_1_2_10_33_1","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1038\/cdd.2009.55","article-title":"An Essential Role for Calcium Flux in Phagocytes for Apoptotic Cell Engulfment and the Anti\u2010Inflammatory Response","volume":"16","author":"Gronski M. A.","year":"2009","journal-title":"Cell Death and Differentiation"},{"key":"e_1_2_10_34_1","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms11284","article-title":"Calcium\u2010Sensing Receptors Signal Constitutive Macropinocytosis and Facilitate the Uptake of NOD2 Ligands in Macrophages","volume":"7","author":"Canton J.","year":"2016","journal-title":"Nature Communications"},{"issue":"1","key":"e_1_2_10_35_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-22558-5","article-title":"Phagocytosis Depends on TRPV2\u2010Mediated Calcium Influx and Requires TRPV2 in Lipids Rafts: Alteration in Macrophages From Patients With Cystic Fibrosis","volume":"8","author":"Leveque M.","year":"2018","journal-title":"Scientific Reports"},{"issue":"19","key":"e_1_2_10_36_1","doi-asserted-by":"crossref","first-page":"4966","DOI":"10.3390\/ijms20194966","article-title":"Mitochondrial Calcium Uptake Is Instrumental to Alternative Macrophage Polarization and Phagocytic 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