{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:10:26Z","timestamp":1789168226587,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"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":["82173647"],"award-info":[{"award-number":["82173647"]}],"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":["82271884"],"award-info":[{"award-number":["82271884"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7232089"],"award-info":[{"award-number":["7232089"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n CC\u2010chemokine ligand 2 (CCL2) plays pivotal roles in many osteoimmune disorders, while its role in peri\u2010implantitis is unknown. The main research question aimed to address in this study is investigating the specific roles of CCL2 in peri\u2010implantitis and assessing the preventive and therapeutic effects of bindarit on experimental peri\u2010implantitis.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Firstly, the expression profile of CC\u2010chemokine receptor 2 ligands in human peri\u2010implantitis was ascertained by processing and analyzing datasets from the Gene Expression Omnibus database. Then the experimental peri\u2010implantitis model was established in mice by suture ligation, and the soft tissue inflammation and hard tissue resorption were compared in CCL2 knockout (\n \n Ccl2\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n ) mice and wild\u2010type mice with experimental peri\u2010implantitis to evaluate the impact of CCL2 in vivo by visual examination, microcomputed tomography, hematoxylin\u2010eosin staining, tartrate\u2010resistant acid phosphatase staining, immunohistochemistry staining, flow cytometry, and quantitative real\u2010time polymerase chain reaction. Furthermore, using both preventive and therapeutic administration routes, the effectiveness of bindarit, which inhibited the expression of CCL2, was evaluated in experimental peri\u2010implantitis.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n CCL2 demonstrated a significant predominant expression among the ligands of CC\u2010chemokine receptor 2 in human peri\u2010implantitis. CCL2 was significantly upregulated in the ligature\u2010induced peri\u2010implantitis model (\n p<\/jats:italic>\n \u00a0=\u00a00.0007), and CCL2 deficiency resulted in significantly decreased monocytes\/macrophages infiltration in peri\u2010implant tissue (CD45\n +<\/jats:sup>\n CD11b\n +<\/jats:sup>\n Ly6C\n hi<\/jats:sup>\n ,\n p<\/jats:italic>\n \u00a0=\u00a00.0019; CD45\n +<\/jats:sup>\n CD11b\n +<\/jats:sup>\n F4\/80\n +<\/jats:sup>\n ,\n p<\/jats:italic>\n \u00a0=\u00a00.0261), significantly reduced proinflammatory cytokine production (TNF\u2010\u03b1,\n p<\/jats:italic>\n \u00a0=\u00a00.0333; IL\u20106,\n p<\/jats:italic>\n \u00a0=\u00a00.0194; IL\u20101\u03b2,\n p<\/jats:italic>\n \u00a0=\u00a00.0090), and significant impaired osteoclast activity (TRAP\n +<\/jats:sup>\n cells,\n p<\/jats:italic>\n \u00a0=\u00a00.0240; RANKL,\n p<\/jats:italic>\n \u00a0=\u00a00.0047), ultimately leading to attenuated mucosal inflammation and bone resorption in peri\u2010implantitis. Moreover, treatment with bindarit demonstrated promising preventive and therapeutic effects in experimental peri\u2010implantitis through inhibiting CCL2.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The findings of this study suggest that CCL2 may serve as a potential target for peri\u2010implantitis treatment by mediating peri\u2010implant host immune response to modulate local inflammation and bone resorption, offering a new direction for the development of immunotherapeutic drugs for this condition.<\/jats:p>\n <\/jats:sec>\n \n Plain language summary<\/jats:title>\n Peri\u2010implantitis, an inflammatory condition that impacts the longevity of dental implants, poses considerable challenges due to the limited effectiveness of current treatment methods. This study aimed to understand the role of CC\u2010chemokine ligand 2 (CCL2) in this condition. In our study, CCL2 was discovered to be the primary ligand of CC\u2010chemokine receptor 2 in peri\u2010implantitis. Lab tests using a mouse model revealed that in the absence of CCL2, inflammation and bone loss were reduced. Furthermore, this study confirmed the effect of a drug called bindarit, which inhibits CCL2, in treating experimental peri\u2010implantitis. Investigating the specific roles of CCL2 and assessing the potential benefits of bindarit in managing peri\u2010implantitis provide a scientific foundation for exploring new treatment strategies.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jper.25-0058","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T07:19:36Z","timestamp":1785309576000},"page":"1937-1948","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Roles of CCL2 in peri\u2010implantitis and its potential as a treatment target: An animal study"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2696-7231","authenticated-orcid":false,"given":"Anqi","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Periodontology Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering 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