{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:09:25Z","timestamp":1787015365095,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T00:00:00Z","timestamp":1694390400000},"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":["81970536"],"award-info":[{"award-number":["81970536"]}],"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":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Our previous study revealed that the C\u2010C motif chemokine receptor 2 (CCR2) is a promising target for periodontitis prevention and treatment. However, CCR2 is a receptor with multiple C\u2010C motif chemokine\u00a0ligands (CCLs), including CCL2, CCL7, CCL8, CCL13 and CCL16, and which of these ligands plays a key role in periodontitis remains unclear. The aim of the present study was to explore the key functional ligand of CCR2 in periodontitis and to evaluate the potential of the functional ligand as a therapeutic target for periodontitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>The expression levels and clinical relevance of CCR2, CCL2, CCL7, CCL8, CCL13 and CCL16 were studied using human samples. The role of CCL2 in periodontitis was evaluated by using CCL2 knockout mice and overexpressing CCL2 in the periodontium. The effect of local administration of bindarit in periodontitis was evaluated by preventive and therapeutic medication in a mouse periodontitis model. Microcomputed tomography, haematoxylin and eosin staining, tartrate\u2010resistant acid phosphatase staining, real\u2010time quantitative polymerase chain reaction, enzyme\u2010linked immunosorbent assay, bead\u2010based immunoassays and flow cytometry were used for histomorphology, molecular biology and cytology analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among different ligands of CCR2, only CCL2 was significantly up\u2010regulated in periodontitis gingival tissues and was positively correlated with the severity of periodontitis. Mice lacking CCL2 showed milder inflammation and less bone resorption than wild\u2010type mice, which was accompanied by a reduction in monocyte\/macrophage recruitment. Adeno\u2010associated virus\u20102 vectors overexpressing CCL2 in\n                      <jats:italic>Ccl2<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice gingiva\u00a0reversed the attenuation of periodontitis in a CCR2\u2010dependent manner. In ligation\u2010induced experimental periodontitis, preventive or therapeutic administration of bindarit, a CCL2 synthesis inhibitor, significantly inhibited the production of CCL2, decreased the osteoclast number and bone loss and reduced the expression levels of proinflammatory cytokines TNF\u2010\u03b1, IL\u20106 and IL\u20101\u03b2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CCL2 is a pivotal chemokine that binds to CCR2 during the progression of periodontitis, and targeting CCL2 may be a feasible option for controlling periodontitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jcpe.13872","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:41:08Z","timestamp":1694479268000},"page":"1644-1657","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["<scp>CCL2<\/scp>\n                    is a key regulator and therapeutic target for periodontitis"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2491-5569","authenticated-orcid":false,"given":"Wenting","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Periodontology, National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology Peking University School and Hospital of Stomatology  Beijing 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