Ccr2, short for CC chemokine receptor 2, is a key receptor in the chemokine signaling pathways. It interacts with chemokine ligand CCL2, and the CCL2-Ccr2 axis is involved in numerous biological processes, including cell migration, immune response modulation, and tissue repair. Genetic models, such as knockout (KO) mouse models, have been crucial in understanding its functions.

In various disease conditions, Ccr2 has shown significant roles. In cancer, blocking the CCL2/Ccr2 axis via Ccr2 knockout or using a Ccr2 antagonist inhibits malignant growth, metastasis, and postsurgical recurrence in murine models of hepatocellular carcinoma, suggesting its potential as a therapeutic target [5]. In cardiovascular diseases, the CCL2-Ccr2 axis has been implicated in the development and progression of heart failure, atherosclerosis, coronary atherosclerotic heart disease, hypertension, and myocardial disease, though clinical translation remains challenging [1]. In pulmonary hypertension, deleting either Ccr2 in macrophages or pulmonary-artery smooth muscle cells attenuated the growth response, and dual targeting of Ccr2 and Ccr5 was more effective in preventing or reversing the disease in mouse models [2]. In orthodontic tooth movement and alveolar bone remodeling, blocking Ccr2 significantly reduced the progression of orthodontic tooth movement, indicating its role in macrophage-mediated local inflammation [3]. In chronic headache-related sensitization, Ccr2 global knockout mice did not show acute or persistent facial skin hypersensitivity induced by repeated nitroglycerin administration, suggesting the CCL2-Ccr2 signalling in macrophages and T cells is required for chronic headache-related sensitization [4]. In osteoarthritis, mice lacking Ccr2 were protected against the disease with a reduction in local monocyte/macrophage numbers in their joints, and blocking CCL2/Ccr2 signalling attenuated macrophage accumulation, synovitis, and cartilage damage in mouse OA [6].

In conclusion, Ccr2 is essential in mediating various biological processes and is involved in multiple disease conditions. Studies using KO/CKO mouse models have significantly contributed to understanding its role in cancer, cardiovascular diseases, pulmonary hypertension, orthodontic-related bone remodeling, chronic headache, and osteoarthritis. These findings highlight Ccr2 as a potential therapeutic target in these disease areas.