{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:38:50Z","timestamp":1790116730239,"version":"4.0.1"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["21221076"],"award-info":[{"award-number":["21221076"]}],"id":[{"id":"10.13039\/501100020884","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008736","name":"Fondo de Fomento al Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["ID24I10282"],"award-info":[{"award-number":["ID24I10282"]}],"id":[{"id":"10.13039\/501100008736","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research and Development Vice-Rectory (VID), University of Chile","award":["ENL25\/25"],"award-info":[{"award-number":["ENL25\/25"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Oral Invest"],"DOI":"10.1007\/s00784-026-06918-4","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T04:26:57Z","timestamp":1778732817000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Immunotherapies based on macrophage reprogramming in periodontitis and apical periodontitis"],"prefix":"10.1007","volume":"30","author":[{"given":"David","family":"Gonz\u00e1lez-Quintanilla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebasti\u00e1n","family":"Castro-Saavedra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Bordagaray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Lucero-Mora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolando","family":"Vernal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Paula-Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"issue":"6","key":"6918_CR1","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1111\/odi.13884","volume":"28","author":"JS Becerra\u2013Ruiz","year":"2022","unstructured":"Becerra\u2013Ruiz JS, Guerrero\u2013Vel\u00e1zquez C, Mart\u00ednez-Esquivias F, Mart\u00ednez\u2010P\u00e9rez LA, Guzm\u00e1n\u2013Flores JM (2022) Innate and adaptive immunity of periodontal disease. From etiology to alveolar bone loss. Oral Dis 28(6):1441\u20131447","journal-title":"Oral Dis"},{"issue":"23","key":"6918_CR2","doi-asserted-by":"publisher","first-page":"7110","DOI":"10.1021\/acs.jafc.2c01710","volume":"70","author":"Y Su","year":"2022","unstructured":"Su Y, Yang F, Chen L, Cheung PCK (2022) Mushroom carboxymethylated \u03b2- <span style=\"font-variant:small-caps;\">d<\/span> -Glucan functions as a macrophage-targeting carrier for iron oxide nanoparticles and an inducer of proinflammatory macrophage polarization for immunotherapy. J Agric Food Chem 70(23):7110\u201321","journal-title":"J Agric Food Chem"},{"issue":"1","key":"6918_CR3","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01452-1","volume":"8","author":"S Chen","year":"2023","unstructured":"Chen S, Saeed A, Liu Q, Jiang Q, Xu H, Xiao GG et al (2023) Macrophages in immunoregulation and therapeutics. Signal Transduct Target Ther 8(1):207","journal-title":"Signal Transduct Target Ther"},{"issue":"1","key":"6918_CR4","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1111\/prd.12032","volume":"63","author":"C Sima","year":"2013","unstructured":"Sima C, Glogauer M (2013) Macrophage subsets and osteoimmunology: tuning of the immunological recognition and effector systems that maintain alveolar bone. Periodontol 2000 63(1):80\u2013101","journal-title":"Periodontol 2000"},{"issue":"39","key":"6918_CR5","doi-asserted-by":"publisher","first-page":"2203680","DOI":"10.1002\/smll.202203680","volume":"18","author":"D Huang","year":"2022","unstructured":"Huang D, Xu K, Huang X, Lin N, Ye Y, Lin S et al (2022) Remotely Temporal Scheduled Macrophage Phenotypic Transition Enables Optimized Immunomodulatory Bone Regeneration. Small 18(39):2203680","journal-title":"Small"},{"issue":"1","key":"6918_CR6","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1111\/odi.12983","volume":"25","author":"LN Zhou","year":"2019","unstructured":"Zhou LN, Bi CS, Gao LN, An Y, Chen F, Chen FM (2019) Macrophage polarization in human gingival tissue in response to periodontal disease. Oral Dis 25(1):265\u2013273","journal-title":"Oral Dis"},{"key":"6918_CR7","doi-asserted-by":"publisher","first-page":"105796","DOI":"10.1016\/j.phrs.2021.105796","volume":"172","author":"M-M Wu","year":"2021","unstructured":"Wu M-M, Wang Q-M, Huang B-Y, Mai C-T, Wang C-L, Wang T-T et al (2021) Dioscin ameliorates murine ulcerative colitis by regulating macrophage polarization. Pharmacol Res 172:105796","journal-title":"Pharmacol Res"},{"issue":"2","key":"6918_CR8","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1111\/imm.13300","volume":"163","author":"VMT Bart","year":"2021","unstructured":"Bart VMT, Pickering RJ, Taylor PR, Ipseiz N (2021) Macrophage reprogramming for therapy. Immunology 163(2):128\u2013144","journal-title":"Immunology"},{"issue":"12","key":"6918_CR9","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1016\/j.archoralbio.2009.10.001","volume":"54","author":"J Chen","year":"2009","unstructured":"Chen J, Gupta T, Barasz JA, Kalajzic Z, Yeh WC, Drissi H et al (2009) Analysis of microarchitectural changes in a mouse temporomandibular joint osteoarthritis model. Arch Oral Biol 54(12):1091\u20131098","journal-title":"Arch Oral Biol"},{"issue":"5","key":"6918_CR10","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1177\/0022034512441946","volume":"91","author":"XD Wang","year":"2012","unstructured":"Wang XD, Kou XX, Mao JJ, Gan YH, Zhou YH (2012) Sustained inflammation induces degeneration of the temporomandibular joint. J Dent Res 91(5):499\u2013505","journal-title":"J Dent Res"},{"key":"6918_CR11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01664","volume":"10","author":"C Alvarez","year":"2019","unstructured":"Alvarez C, Monasterio G, Cavalla F, C\u00f3rdova LA, Hern\u00e1ndez M, Heymann D et al (2019) Osteoimmunology of oral and maxillofacial diseases: translational applications based on biological mechanisms. Front Immunol 10:1664","journal-title":"Front Immunol"},{"issue":"1","key":"6918_CR12","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1146\/annurev-physiol-022516-034339","volume":"79","author":"PJ Murray","year":"2017","unstructured":"Murray PJ (2017) Macrophage polarization. Annu Rev Physiol 79(1):541\u2013566","journal-title":"Annu Rev Physiol"},{"issue":"2","key":"6918_CR13","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.cellsig.2013.11.004","volume":"26","author":"D Zhou","year":"2014","unstructured":"Zhou D, Huang C, Lin Z, Zhan S, Kong L, Fang C et al (2014) Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways. Cell Signal 26(2):192\u20137","journal-title":"Cell Signal"},{"key":"6918_CR14","doi-asserted-by":"crossref","unstructured":"Wang C, Wu Q, Zhuang L, Chen Y, Zhang Q, Wu Y et al (2025) Immunometabolism of macrophages in the bone microenvironment: a new perspective for bone healing therapy. J Adv Res","DOI":"10.1016\/j.jare.2025.07.046"},{"issue":"1","key":"6918_CR15","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/s41392-023-01452-1","volume":"8","author":"S Chen","year":"2023","unstructured":"Chen S, Saeed AFUH, Liu Q, Jiang Q, Xu H, Xiao GG et al (2023) Macrophages in immunoregulation and therapeutics. Signal Transduct Target Therapy 8(1):207","journal-title":"Signal Transduct Target Therapy"},{"key":"6918_CR16","first-page":"195","volume-title":"Periodontitis. 1373","author":"F Cavalla","year":"2022","unstructured":"Cavalla F, Hern\u00e1ndez M (2022) Polarization Profiles of T Lymphocytes and Macrophages Responses in Periodontitis. In: Santi-Rocca J (ed) Periodontitis. 1373. Springer International Publishing, Cham, pp 195\u2013208"},{"issue":"11","key":"6918_CR17","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1016\/j.immuni.2022.10.004","volume":"55","author":"Z Czimmerer","year":"2022","unstructured":"Czimmerer Z, Halasz L, Daniel B, Varga Z, Bene K, Domokos A et al (2022) The epigenetic state of IL-4-polarized macrophages enables inflammatory cistromic expansion and extended synergistic response to TLR ligands. Immunity 55(11):2006\u201326.e6","journal-title":"Immunity"},{"issue":"1","key":"6918_CR18","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/s41536-021-00193-5","volume":"6","author":"J Sapudom","year":"2021","unstructured":"Sapudom J, Karaman S, Mohamed WKE, Garcia-Sabat\u00e9 A, Quartey BC, Teo JCM (2021) 3D in vitro M2 macrophage model to mimic modulation of tissue repair. npj Regen Med 6(1):83","journal-title":"npj Regen Med"},{"issue":"5","key":"6918_CR19","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1631\/jzus.B2100930","volume":"23","author":"P Li","year":"2022","unstructured":"Li P, Ma C, Li J, You S, Dang L, Wu J et al (2022) Proteomic characterization of four subtypes of M2 macrophages derived from human THP-1 cells. J Zhejiang Univ Sci B 23(5):407\u201322","journal-title":"J Zhejiang Univ Sci B"},{"issue":"1","key":"6918_CR20","doi-asserted-by":"publisher","first-page":"e23223","DOI":"10.1016\/j.heliyon.2023.e23223","volume":"10","author":"L Chen","year":"2024","unstructured":"Chen L, Mei W, Song J, Chen K, Ni W, Wang L et al (2024) CD163 protein inhibits lipopolysaccharide-induced macrophage transformation from M2 to M1 involved in disruption of the TWEAK\u2013Fn14 interaction. Heliyon 10(1):e23223","journal-title":"Heliyon"},{"issue":"8","key":"6918_CR21","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1111\/jcpe.13156","volume":"46","author":"C Garaicoa-Pazmino","year":"2019","unstructured":"Garaicoa-Pazmino C, Fretwurst T, Squarize CH, Berglundh T, Giannobile WV, Larsson L et al (2019) Characterization of macrophage polarization in periodontal disease. J Clin Periodontol 46(8):830\u20139","journal-title":"J Clin Periodontol"},{"key":"6918_CR22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00330","volume":"11","author":"A Almubarak","year":"2020","unstructured":"Almubarak A, Tanagala KKK, Papapanou PN, Lalla E, Momen-Heravi F (2020) Disruption of monocyte and macrophage homeostasis in periodontitis. Front Immunol 11:330","journal-title":"Front Immunol"},{"issue":"5","key":"6918_CR23","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1111\/iej.13467","volume":"54","author":"CS Tib\u00farcio-Machado","year":"2021","unstructured":"Tib\u00farcio-Machado CS, Michelon C, Zanatta FB, Gomes MS, Marin JA, Bier CA (2021) The global prevalence of apical periodontitis: a systematic review and meta\u2010analysis. Int Endod J 54(5):712\u2013735","journal-title":"Int Endod J"},{"issue":"1","key":"6918_CR24","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.cden.2016.08.009","volume":"61","author":"N Chugal","year":"2017","unstructured":"Chugal N, Mallya SM, Kahler B, Lin LM (2017) Endodontic treatment outcomes. Dent Clin North Am 61(1):59\u201380","journal-title":"Dent Clin North Am"},{"issue":"6","key":"6918_CR25","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1097\/PRS.0000000000011437","volume":"154","author":"AY Li","year":"2024","unstructured":"Li AY, Park MJ, Fick J, Ousterhout DK, Deschamps-Braly JC (2024) Perioperative estrogen hormonal therapy does not increase venous thromboembolism risk in facial feminization surgery. Plast Reconstr Surg 154(6):1309\u20131315","journal-title":"Plast Reconstr Surg"},{"key":"6918_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26052107","author":"J Brancewicz","year":"2025","unstructured":"Brancewicz J, W\u00f3jcik N, Sarnowska Z, Robak J, Kr\u00f3l M (2025) The multifaceted role of macrophages in biology and diseases. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms26052107","journal-title":"Int J Mol Sci"},{"issue":"12","key":"6918_CR27","doi-asserted-by":"publisher","first-page":"4571","DOI":"10.1007\/s00784-020-03324-2","volume":"24","author":"P Veloso","year":"2020","unstructured":"Veloso P, Fern\u00e1ndez A, Terraza-Aguirre C, \u00c1lvarez C, Vernal R, Escobar A et al (2020) Macrophages skew towards M1 profile through reduced CD163 expression in symptomatic apical periodontitis. Clin Oral Investig 24(12):4571\u201381","journal-title":"Clin Oral Investig"},{"issue":"28","key":"6918_CR28","doi-asserted-by":"publisher","first-page":"e2416159","DOI":"10.1002\/advs.202416159","volume":"12","author":"Y Yao","year":"2025","unstructured":"Yao Y, Yin Y, Shuai F, Lam W, Zhou T, Xie Y et al (2025) M2 Macrophage-Derived Extracellular Vesicles Reprogram Immature Neutrophils into Anxa1(hi) Neutrophils to Enhance Inflamed Bone Regeneration. Adv Sci (Weinh) 12(28):e2416159","journal-title":"Adv Sci (Weinh)"},{"key":"6918_CR29","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.biomaterials.2017.12.025","volume":"196","author":"J Pajarinen","year":"2019","unstructured":"Pajarinen J, Lin T, Gibon E, Kohno Y, Maruyama M, Nathan K et al (2019) Mesenchymal stem cell-macrophage crosstalk and bone healing. Biomaterials 196:80\u201389","journal-title":"Biomaterials"},{"key":"6918_CR30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.763334","volume":"12","author":"X Sun","year":"2021","unstructured":"Sun X, Gao J, Meng X, Lu X, Zhang L, Chen R (2021) Polarized macrophages in periodontitis: characteristics, function, and molecular signaling. Front Immunol 12:763334","journal-title":"Front Immunol"},{"key":"6918_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.109790","volume":"116","author":"W Wang","year":"2023","unstructured":"Wang W, Chu Y, Zhang P, Liang Z, Fan Z, Guo X et al (2023) Targeting macrophage polarization as a promising therapeutic strategy for the treatment of osteoarthritis. Int Immunopharmacol 116:109790","journal-title":"Int Immunopharmacol"},{"issue":"18","key":"6918_CR32","doi-asserted-by":"publisher","first-page":"13873","DOI":"10.3390\/ijms241813873","volume":"24","author":"R Liu","year":"2023","unstructured":"Liu R, Liu S, Wu S, Xia M, Liu W, Wang L et al (2023) Milk-Derived Small Extracellular Vesicles Promote Osteogenic Differentiation and Inhibit Inflammation via microRNA-21. Int J Mol Sci 24(18):13873","journal-title":"Int J Mol Sci"},{"key":"6918_CR33","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12020441","author":"Y Wang","year":"2024","unstructured":"Wang Y, Mao J, Jiang N, Shi X (2024) Multifunctional exosomes derived from M2 macrophages with enhanced odontogenesis, neurogenesis and angiogenesis for regenerative endodontic therapy: An in vitro and in vivo investigation. Biomedicines. https:\/\/doi.org\/10.3390\/biomedicines12020441","journal-title":"Biomedicines"},{"issue":"2","key":"6918_CR34","doi-asserted-by":"publisher","first-page":"272","DOI":"10.3390\/biology11020272","volume":"11","author":"MR Czerniuk","year":"2022","unstructured":"Czerniuk MR, Surma S, Roma\u0144czyk M, Nowak JM, Wojtowicz A, Filipiak KJ (2022) Unexpected relationships: periodontal diseases: atherosclerosis\u2013plaque destabilization? From the teeth to a coronary event. Biology 11(2):272","journal-title":"Biology"},{"issue":"1","key":"6918_CR35","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1111\/prd.12451","volume":"90","author":"L Nibali","year":"2022","unstructured":"Nibali L, Gkranias N, Mainas G, Di Pino A (2022) Periodontitis and implant complications in diabetes. Periodontol 2000 90(1):88\u2013105","journal-title":"Periodontol 2000"},{"issue":"2","key":"6918_CR36","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1002\/JPER.21-0226","volume":"94","author":"SMC Todescan","year":"2023","unstructured":"Todescan SMC, Schroth RJ, Dean H, Wicklow B, Michel-Crosato E, Sellers E (2023) High prevalence of periodontitis in children and adolescents with type 2 diabetes. J Periodontol 94(2):174\u2013183","journal-title":"J Periodontol"},{"issue":"1","key":"6918_CR37","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/nri3785","volume":"15","author":"G Hajishengallis","year":"2015","unstructured":"Hajishengallis G (2015) Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol 15(1):30\u201344","journal-title":"Nat Rev Immunol"},{"issue":"2","key":"6918_CR38","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1177\/0022034518805984","volume":"98","author":"Z Zhuang","year":"2019","unstructured":"Zhuang Z, Yoshizawa-Smith S, Glowacki A, Maltos K, Pacheco C, Shehabeldin M et al (2019) Induction of M2 Macrophages Prevents Bone Loss in Murine Periodontitis Models. J Dent Res 98(2):200\u2013208","journal-title":"J Dent Res"},{"issue":"7","key":"6918_CR39","doi-asserted-by":"publisher","first-page":"2650","DOI":"10.1073\/pnas.1324140111","volume":"111","author":"A-M Bulau","year":"2014","unstructured":"Bulau A-M, Nold MF, Li S, Nold-Petry CA, Fink M, Mansell A et al (2014) Role of caspase-1 in nuclear translocation of IL-37, release of the cytokine, and IL-37 inhibition of innate immune responses. Proc Natl Acad Sci U S A 111(7):2650\u20135","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"6918_CR40","doi-asserted-by":"publisher","first-page":"e1004462","DOI":"10.1371\/journal.ppat.1004462","volume":"10","author":"S Moretti","year":"2014","unstructured":"Moretti S, Bozza S, Oikonomou V, Renga G, Casagrande A, Iannitti RG et al (2014) IL-37 Inhibits Inflammasome Activation and Disease Severity in Murine Aspergillosis. PLoS Pathog 10(11):e1004462","journal-title":"PLoS Pathog"},{"issue":"4","key":"6918_CR41","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1038\/ni.3103","volume":"16","author":"CA Nold-Petry","year":"2015","unstructured":"Nold-Petry CA, Lo CY, Rudloff I, Elgass KD, Li S, Gantier MP et al (2015) IL-37 requires the receptors IL-18R\u03b1 and IL-1R8 (SIGIRR) to carry out its multifaceted anti-inflammatory program upon innate signal transduction. Nat Immunol 16(4):354\u201365","journal-title":"Nat Immunol"},{"key":"6918_CR42","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.archoralbio.2017.03.006","volume":"96","author":"J Yang","year":"2018","unstructured":"Yang J, Zhu Y, Duan D, Wang P, Xin Y, Bai L et al (2018) Enhanced activity of macrophage M1\/M2 phenotypes in periodontitis. Arch Oral Biol 96:234\u201342","journal-title":"Arch Oral Biol"},{"issue":"1","key":"6918_CR43","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1111\/jre.13196","volume":"59","author":"L Yang","year":"2024","unstructured":"Yang L, Tao W, Xie C, Chen Q, Zhao Y, Zhang L et al (2024) Interleukin-37 ameliorates periodontitis development by inhibiting NLRP3 inflammasome activation and modulating M1 \/ M2 macrophage polarization. J Periodontal Res 59(1):128\u201339","journal-title":"J Periodontal Res"},{"issue":"5","key":"6918_CR44","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1002\/JPER.24-0405","volume":"96","author":"H Mu","year":"2025","unstructured":"Mu H, Yang B, Wang Y, Wang S, Yu W, Jia M et al (2025) Inhibition of fibulin-3 ameliorates periodontal inflammation through reducing M1 macrophage polarization via EGFR\/PI3K\/AKT pathway. J Periodontol 96(5):440\u2013454","journal-title":"J Periodontol"},{"issue":"9","key":"6918_CR45","doi-asserted-by":"publisher","first-page":"2305490","DOI":"10.1002\/smll.202305490","volume":"20","author":"P Ming","year":"2024","unstructured":"Ming P, Liu Y, Yu P, Jiang X, Yuan L, Cai S et al (2024) A Biomimetic Se-nHA\/PC Composite Microsphere with Synergistic Immunomodulatory and Osteogenic Ability to Activate Bone Regeneration in Periodontitis. Small 20(9):2305490","journal-title":"Small"},{"issue":"11","key":"6918_CR46","doi-asserted-by":"publisher","first-page":"5026","DOI":"10.1016\/j.apsb.2024.07.008","volume":"14","author":"Y Zhang","year":"2024","unstructured":"Zhang Y, Shi J, Zhu J, Ding X, Wei J, Jiang X et al (2024) Immunometabolic rewiring in macrophages for periodontitis treatment via nanoquercetin-mediated leverage of glycolysis and OXPHOS. Acta Pharm Sin B 14(11):5026\u20135036","journal-title":"Acta Pharm Sin B"},{"key":"6918_CR47","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.actbio.2020.12.046","volume":"122","author":"Y Nakao","year":"2021","unstructured":"Nakao Y, Fukuda T, Zhang Q, Sanui T, Shinjo T, Kou X et al (2021) Exosomes from TNF-\u03b1-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal bone loss. Acta Biomater 122:306\u2013324","journal-title":"Acta Biomater"},{"key":"6918_CR48","doi-asserted-by":"crossref","unstructured":"Wu Y, Song LT, Li JS, Zhu DW, Jiang SY, Deng JY (2017) MicroRNA-126 Regulates Inflammatory Cytokine Secretion in Human Gingival Fibroblasts Under High Glucose via Targeting Tumor Necrosis Factor Receptor Associated Factor 6. J Periodontol 88(11)","DOI":"10.1902\/jop.2017.170091"},{"key":"6918_CR49","doi-asserted-by":"publisher","first-page":"105686","DOI":"10.1016\/j.archoralbio.2023.105686","volume":"150","author":"J Li","year":"2023","unstructured":"Li J, Liu Y, Lai W, Song L, Deng J, Li C et al (2023) MicroRNA-126 regulates macrophage polarization to prevent the resorption of alveolar bone in diabetic periodontitis. Arch Oral Biol 150:105686","journal-title":"Arch Oral Biol"},{"issue":"5","key":"6918_CR50","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1007\/s10753-023-01850-1","volume":"46","author":"X Guo","year":"2023","unstructured":"Guo X, Huang Z, Ge Q, Yang L, Liang D, Huang Y et al (2023) Glipizide Alleviates Periodontitis Pathogenicity via Inhibition of Angiogenesis, Osteoclastogenesis and M1\/M2 Macrophage Ratio in Periodontal Tissue. Inflammation 46(5):1917\u20131931","journal-title":"Inflammation"},{"key":"6918_CR51","doi-asserted-by":"publisher","first-page":"114279","DOI":"10.1016\/j.intimp.2025.114279","volume":"150","author":"T Bian","year":"2025","unstructured":"Bian T, Li H, Liu H, Guo M, Zhang Y, Hu P et al (2025) Apabetalone alleviates ligature-induced periodontitis by inhibiting M1 macrophage polarization via an immunometabolic shift. Int Immunopharmacol 150:114279","journal-title":"Int Immunopharmacol"},{"key":"6918_CR52","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.603817","volume":"7","author":"Y Miao","year":"2020","unstructured":"Miao Y, He L, Qi X, Lin X (2020) Injecting immunosuppressive M2 macrophages alleviates the symptoms of periodontitis in mice. Front Mol Biosci 7:603817","journal-title":"Front Mol Biosci"},{"issue":"12","key":"6918_CR53","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1016\/j.joen.2009.09.028","volume":"35","author":"JL Gutmann","year":"2009","unstructured":"Gutmann JL, Baumgartner JC, Gluskin AH, Hartwell GR, Walton RE (2009) Identify and define all diagnostic terms for periapical\/periradicular health and disease states. J Endod 35(12):1658\u20131674","journal-title":"J Endod"},{"issue":"12","key":"6918_CR54","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1177\/0022034516660509","volume":"95","author":"JM Liljestrand","year":"2016","unstructured":"Liljestrand JM, M\u00e4ntyl\u00e4 P, Paju S, Buhlin K, Kopra KAE, Persson GR et al (2016) Association of endodontic lesions with coronary artery disease. J Dent Res 95(12):1358\u201365","journal-title":"J Dent Res"},{"issue":"2","key":"6918_CR55","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.joen.2018.11.014","volume":"45","author":"M Garrido","year":"2019","unstructured":"Garrido M, C\u00e1rdenas AM, Astorga J, Quinlan F, Vald\u00e9s M, Chaparro A et al (2019) Elevated Systemic Inflammatory Burden and Cardiovascular Risk in Young Adults with Endodontic Apical Lesions. J Endod 45(2):111\u2013115","journal-title":"J Endod"},{"issue":"3","key":"6918_CR56","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1111\/j.1600-9657.1994.tb00536.x","volume":"10","author":"A Akamine","year":"1994","unstructured":"Akamine A, Hashinguchi I, Toriya Y, Maeda K (1994) Immnohistochemical examination on the localization of macrophages and plasma cells in induced rat periapical lesions. Dent Traumatol 10(3):121\u2013128","journal-title":"Dent Traumatol"},{"issue":"1","key":"6918_CR57","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S0099-2399(06)80023-3","volume":"20","author":"T Okiji","year":"1994","unstructured":"Okiji T, Kawashima N, Kosaka T, Kobayashi C, Suda H (1994) Distribution of la antigen-expressing nonlymphoid cells in various stages of induced periapical lesions in rat molars. J Endod 20(1):27\u201331","journal-title":"J Endod"},{"issue":"10","key":"6918_CR58","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1016\/j.joen.2019.06.014","volume":"45","author":"M Weber","year":"2019","unstructured":"Weber M, Ries J, B\u00fcttner-Herold M, Geppert CI, Kesting M, Wehrhan F (2019) Differences in inflammation and bone resorption between apical granulomas, radicular cysts, and dentigerous cysts. J Endod 45(10):1200\u20131208","journal-title":"J Endod"},{"key":"6918_CR59","doi-asserted-by":"publisher","DOI":"10.1590\/1807-3107bor-2019.vol33.0047","volume":"33","author":"GMD Fran\u00e7a","year":"2019","unstructured":"Fran\u00e7a GMD, Carmo AFD, Costa Neto H, Andrade ALDLD, Lima KCD, Galv\u00e3o HC (2019) Macrophages subpopulations in chronic periapical lesions according to clinical and morphological aspects. Braz Oral Res 33:e047","journal-title":"Braz Oral Res"},{"key":"6918_CR60","doi-asserted-by":"publisher","DOI":"10.1111\/iej.14138","author":"S Visarnta","year":"2024","unstructured":"Visarnta S, Ratisoontorn C, Panichuttra A, Sinpitaksakul P, Chantarangsu S, Dhanuthai K (2024) Macrophage polarization in human periapical lesions in relation to histopathological diagnosis, clinical features and lesion volume: An ex vivo study. Int Endod J. https:\/\/doi.org\/10.1111\/iej.14138","journal-title":"Int Endod J"},{"issue":"4","key":"6918_CR61","doi-asserted-by":"publisher","first-page":"488","DOI":"10.3390\/bioengineering10040488","volume":"10","author":"Z Arias","year":"2023","unstructured":"Arias Z, Nizami MZI, Chen X, Chai X, Xu B, Kuang C et al (2023) Recent Advances in Apical Periodontitis Treatment: A Narrative Review. Bioengineering 10(4):488","journal-title":"Bioengineering"},{"key":"6918_CR62","first-page":"1","volume":"2022","author":"Y Zhao","year":"2022","unstructured":"Zhao Y, Huang Y, Liu H, Tan K, Wang R, Jia L et al (2022) Macrophages with Different Polarization Phenotypes Influence Cementoblast Mineralization through Exosomes. Stem Cells Int 2022:1\u201316","journal-title":"Stem Cells Int"},{"issue":"2","key":"6918_CR63","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41368-018-0015-0","volume":"10","author":"K Hirai","year":"2018","unstructured":"Hirai K, Furusho H, Hirota K, Sasaki H (2018) Activation of hypoxia-inducible factor 1 attenuates periapical inflammation and bone loss. Int J Oral Sci 10(2):12","journal-title":"Int J Oral Sci"},{"issue":"3","key":"6918_CR64","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1097\/SHK.0b013e318225ad7e","volume":"36","author":"E Hams","year":"2011","unstructured":"Hams E, Saunders SP, Cummins EP, O\u2019Connor A, Tambuwala MT, Gallagher WM et al (2011) The Hydroxylase Inhibitor Dimethyloxallyl Glycine Attenuates Endotoxic Shock Via Alternative Activation of Macrophages and IL-10 Production by B1 Cells. Shock 36(3):295\u2013302","journal-title":"Shock"},{"key":"6918_CR65","doi-asserted-by":"crossref","unstructured":"Bandarra D, Biddlestone J, Mudie S, Muller HA, Rocha S (2014) HIF-1\u03b1 restricts NF-\u03baB dependent gene expression to control innate immunity signals. Dis Models Mech dmm017285","DOI":"10.1242\/dmm.017285"},{"key":"6918_CR66","doi-asserted-by":"publisher","first-page":"e20220316","DOI":"10.1590\/1678-7757-2022-0316","volume":"30","author":"X Chen","year":"2022","unstructured":"Chen X, Dou J, Fu Z, Qiu Y, Zou L, Huang D et al (2022) Macrophage M1 polarization mediated via the IL-6\/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalis. J Appl Oral Sci 30:e20220316","journal-title":"J Appl Oral Sci"},{"issue":"3","key":"6918_CR67","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1093\/jac\/dkn007","volume":"61","author":"BS Murphy","year":"2008","unstructured":"Murphy BS, Sundareshan V, Cory TJ, Hayes D, Anstead MI, Feola DJ (2008) Azithromycin alters macrophage phenotype. J Antimicrob Chemother 61(3):554\u2013560","journal-title":"J Antimicrob Chemother"},{"issue":"5","key":"6918_CR68","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1002\/jcp.24259","volume":"228","author":"SC Gannon","year":"2013","unstructured":"Gannon SC, Cantley MD, Haynes DR, Hirsch R, Bartold PM (2013) Azithromycin suppresses human osteoclast formation and activity in vitro. J Cell Physiol 228(5):1098\u20131107","journal-title":"J Cell Physiol"},{"issue":"11","key":"6918_CR69","doi-asserted-by":"publisher","first-page":"1648","DOI":"10.1016\/j.joen.2020.07.028","volume":"46","author":"AC Andrada","year":"2020","unstructured":"Andrada AC, Azuma MM, Furusho H, Hirai K, Xu S, White RR et al (2020) Immunomodulation Mediated by Azithromycin in Experimental Periapical Inflammation. J Endod 46(11):1648\u20131654","journal-title":"J Endod"},{"issue":"5","key":"6918_CR70","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/S1097-2765(00)80067-2","volume":"1","author":"DR Hsu","year":"1998","unstructured":"Hsu DR, Economides AN, Wang X, Eimon PM, Harland RM (1998) The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities. Mol Cell 1(5):673\u2013683","journal-title":"Mol Cell"},{"issue":"5","key":"6918_CR71","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1080\/08923973.2024.2392196","volume":"46","author":"XY Guan","year":"2024","unstructured":"Guan XY, Wei ZC, Wang YT, Li WL, Mu WL, Seyam A et al (2024) Blocking Gremlin1 inhibits M1 macrophage polarization through Notch1\/Hes1 signaling pathway in apical periodontitis. Immunopharmacol Immunotoxicol 46(5):703\u201314","journal-title":"Immunopharmacol Immunotoxicol"},{"issue":"5","key":"6918_CR72","doi-asserted-by":"publisher","first-page":"1962","DOI":"10.3390\/ma15051962","volume":"15","author":"X Yang","year":"2022","unstructured":"Yang X, Tian J, Li M, Chen W, Liu H, Wang Z et al (2022) Biocompatibility of a New Calcium Silicate-Based Root Canal Sealer Mediated via the Modulation of Macrophage Polarization in a Rat Model. Materials 15(5):1962","journal-title":"Materials"},{"issue":"10","key":"6918_CR73","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1016\/j.joen.2018.07.005","volume":"44","author":"H-W Yeh","year":"2018","unstructured":"Yeh H-W, Chiang C-F, Chen P-H, Su C-C, Wu Y-C, Chou L et al (2018) Axl Involved in Mineral Trioxide Aggregate Induces Macrophage Polarization. J Endod 44(10):1542\u20131548","journal-title":"J Endod"}],"container-title":["Clinical Oral Investigations"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00784-026-06918-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00784-026-06918-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00784-026-06918-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T07:03:52Z","timestamp":1782457432000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00784-026-06918-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":73,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["6918"],"URL":"https:\/\/doi.org\/10.1007\/s00784-026-06918-4","relation":{},"ISSN":["1436-3771"],"issn-type":[{"value":"1436-3771","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]},"assertion":[{"value":"6 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"234"}}