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Aim: CCR2 (C‐C chemokine receptor type 2) plays a crucial role in inflammatory and bone metabolic diseases; however, its role in peri‐implantitis remains unclear. This study aimed to explore whether CCR2 contributes to peri‐implantitis and the treatment effects of cenicriviroc (CVC) on peri‐implant inflammation and bone resorption. Materials and Methods: The expression of CCR2 was studied using clinical tissue analysis and an in vivo peri‐implantitis model. The role of CCR2 in promoting inflammation and bone resorption in peri‐implantitis was evaluated in Ccr2−/− mice and wild‐type mice. The effect of CVC on peri‐implantitis was evaluated using systemic and local dosage forms. Results: Human peri‐implantitis tissues showed increased CCR2 and CCL2 levels, which were positively correlated with bone loss around the implants. Knocking out Ccr2 in an experimental model of peri‐implantitis resulted in decreased monocyte and macrophage infiltration, reduced pro‐inflammatory cytokine generation and impaired osteoclast activity, leading to reduced inflammation and bone loss around the implants. Treatment with CVC ameliorated bone loss in experimental peri‐implantitis. Conclusions: CCR2 may be a potential target for peri‐implantitis treatment by harnessing the immune‐inflammatory response to modulate the local inflammation and osteoclast activity. [ABSTRACT FROM AUTHOR]

Aim: Our previous study revealed that the C‐C motif chemokine receptor 2 (CCR2) is a promising target for periodontitis prevention and treatment. However, CCR2 is a receptor with multiple C‐C motif chemokine ligands (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. Materials and Methods: 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‐resistant acid phosphatase staining, real‐time quantitative polymerase chain reaction, enzyme‐linked immunosorbent assay, bead‐based immunoassays and flow cytometry were used for histomorphology, molecular biology and cytology analysis. Results: Among different ligands of CCR2, only CCL2 was significantly up‐regulated 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‐type mice, which was accompanied by a reduction in monocyte/macrophage recruitment. Adeno‐associated virus‐2 vectors overexpressing CCL2 in Ccl2−/− mice gingiva reversed the attenuation of periodontitis in a CCR2‐dependent manner. In ligation‐induced 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‐α, IL‐6 and IL‐1β. Conclusions: 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. [ABSTRACT FROM AUTHOR]