{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T03:37:17Z","timestamp":1793504237227,"version":"4.5.0"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016070","name":"ITI Foundation","doi-asserted-by":"publisher","award":["2021\u20101634"],"award-info":[{"award-number":["2021\u20101634"]}],"id":[{"id":"10.13039\/501100016070","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":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate the impact of macrophage depletion on bone loss and inflammatory responses in a mouse model of peri\u2010implantitis, assessing macrophage depletion potential as a therapeutic strategy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Using 6\u2010week\u2010old male C57BL\/6 mice, peri\u2010implantitis was induced by placing a silk ligature around osteointegrated dental implants. Mice were divided into three groups: Healthy control (Healthy group); peri\u2010implantitis with liposomal phosphate\u2010buffered saline (PBS group); and peri\u2010implantitis with liposomal clodronate for macrophage depletion (CLOD group). Two weeks after ligature placement, micro\u2010CT, histological and real\u2010time PCR analyses were performed to assess bone density, leukocyte infiltration and cytokine levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The CLOD group showed a significantly higher bone\u2010to\u2010implant contact (74%) and bone volume relative to total volume (79%) compared to the PBS group (53% and 54%, respectively) and Healthy group (64% and 66%, respectively). Histological analysis revealed significantly reduced leukocyte and macrophage counts in the CLOD group. Additionally, TNF\u2010\u03b1 and IL\u201010 levels were significantly decreased in the CLOD group compared with the PBS group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Macrophage depletion effectively reduces bone loss and inflammation in peri\u2010implantitis. This study highlights targeting macrophages as a promising approach for managing peri\u2010implantitis, although further research is needed to optimize therapeutic strategies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jcpe.14120","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T01:34:21Z","timestamp":1744767261000},"page":"898-906","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Macrophage Depletion Reduces Bone Loss and Alters Inflammatory Responses: A Mouse Peri\u2010Implantitis Model"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8736-9753","authenticated-orcid":false,"given":"Ofir","family":"Ginesin","sequence":"first","affiliation":[{"name":"Department of Periodontology School of Graduate Dentistry, Rambam Health Care Campus  Haifa Israel"},{"name":"Laboratory for Bone Repair CRIR Institute, Rambam Health Care Campus  Haifa Israel"},{"name":"Rappaport Faculty of Medicine Technion \u2013 Israeli Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0105-6703","authenticated-orcid":false,"given":"Benjamin R.","family":"Coyac","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Graduate Dentistry, Rambam Health Care Campus  Haifa Israel"},{"name":"Craniofacial Ossification Laboratory, Department of Oral Biology Goldschleger School of Dental Medicine, Faculty of Medical and Health Sciences, Tel Aviv University  Tel Aviv\u2010Yafo Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofri","family":"Doppelt\u2010Flikshtain","sequence":"additional","affiliation":[{"name":"Laboratory for Bone Repair CRIR Institute, Rambam Health Care Campus  Haifa Israel"},{"name":"Rappaport Faculty of Medicine Technion \u2013 Israeli Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5500-7961","authenticated-orcid":false,"given":"Yaniv","family":"Mayer","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Graduate Dentistry, Rambam Health Care Campus  Haifa Israel"},{"name":"Rappaport Faculty of Medicine Technion \u2013 Israeli Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eran","family":"Gabay","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Graduate Dentistry, Rambam Health Care Campus  Haifa Israel"},{"name":"Rappaport Faculty of Medicine Technion \u2013 Israeli Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal","family":"Berg","sequence":"additional","affiliation":[{"name":"Laboratory for Bone Repair CRIR Institute, Rambam Health Care Campus  Haifa Israel"},{"name":"Rappaport Faculty of Medicine Technion \u2013 Israeli Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yotam","family":"Bar\u2010On","sequence":"additional","affiliation":[{"name":"Department of Immunology Rappaport Faculty of Medicine, Technion \u2013 Israeli Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4940-6533","authenticated-orcid":false,"given":"Hadar","family":"Zigdon\u2010Giladi","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Graduate Dentistry, Rambam Health Care Campus  Haifa Israel"},{"name":"Laboratory for Bone Repair CRIR Institute, Rambam Health Care Campus  Haifa Israel"},{"name":"Rappaport Faculty of Medicine Technion \u2013 Israeli Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1902\/JOP.2010.100425"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.17\u20100739"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/PRD.12549"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.31744\/EINSTEIN_JOURNAL\/2024AO0396"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514551754"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v024a08"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345211009463\/FORMAT\/EPUB"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/CLR.12128"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.AJPATH.2015.06.001"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.03.013"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.18\u20100748"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910608500208"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.DEVCEL.2020.10.023"},{"issue":"2","key":"e_1_2_9_15_1","first-page":"131","article-title":"Cytokine and Metalloproteinases in Gingival Fluid From Patients With Chronic Periodontitis","volume":"57","author":"Escalona L. A.","year":"2016","journal-title":"Investigaci\u00f3n Cl\u00ednica"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/clr.13568"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2353\/AJPATH.2010.090608"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00784\u2010020\u201003556\u20102"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12483"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00784\u2010023\u201005168\u2010Y\/TABLES\/4"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/J.0303\u20106979.2003.00425.X"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.INTIMP.2009.06.002"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.ACTBIO.2012.09.009"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12817"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.08.029"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/CLR.13885"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2023.116899"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/JCPE.13982"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/FBIOE.2024.1291880"},{"issue":"1","key":"e_1_2_9_30_1","first-page":"42","article-title":"Detection of Inflammatory Cytokine Messenger RNA (mRNA)\u2010Expressing Cells in Human Inflamed Gingiva by Combined In\u00a0Situ Hybridization and Immunohistochemistry","volume":"76","author":"Matsuki Y.","year":"1992","journal-title":"Immunology"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2009.090015"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034518821685"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20107837\u20103_23\/COVER"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.07.021"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/clr.12770"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1902\/JOP.2008.070616"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.11607\/JOMI.10780"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.04.052"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12032"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3109\/08820139.2013.822766"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1902\/JOP.1991.62.8.504"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/JBC.M710314200"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/CLR.13894"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010019\u20100178\u20108"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PPAT.1006949"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12735"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/HEP.510230544"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1081\/lpr\u2010120004780"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/ODI.14935"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034518777973\/ASSET\/IMAGES\/LARGE\/10.1177_0022034518777973\u2010FIG5.JPEG"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1177\/039463200702001s14"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.57775"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12633"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.36978"}],"container-title":["Journal of Clinical Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcpe.14120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T07:56:50Z","timestamp":1751270210000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcpe.14120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,15]]},"references-count":53,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/jcpe.14120"],"URL":"https:\/\/doi.org\/10.1111\/jcpe.14120","archive":["Portico"],"relation":{},"ISSN":["0303-6979","1600-051X"],"issn-type":[{"value":"0303-6979","type":"print"},{"value":"1600-051X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,15]]},"assertion":[{"value":"2024-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}