Skeletal Muscle Regeneration is Dependent upon CCR2 Expression on Bone Marrow (BM)‐Derived Cells

CC chemokine receptor 2 (CCR2) is essential for macrophage recruitment and macrophages play an important role in muscle regeneration. We have shown that monocyte/macrophage recruitment was dependent on CCR2 expression on BM‐derived cells; the current study defines the role of CCR2 expression on muscle regeneration. Using radiation chimeras, WT or CCR2−/−male mice received transplanted BM from WT or CCR2−/−mice creating 4 groups (Donor BM→host): WT→WT, CCR2→CCR2, WT→CCR2 and CCR2→WT. Mice were sacrificed at baseline and days 14, 21, and 28 after cardiotoxin injury. Injury, necrosis, myofiber size, and fat accumulation were histomorphometrically assessed. While tissue injury was similar in all groups, residual myonecrosis at 14 days post‐injury was greater in mice receiving CCR2−/− BM. At baseline, myofiber cross sectional area (CSA) was similar in all groups, and CSA of regenerated fibers was decreased compared to baseline at all time points in all groups. Mice receiving WT BM had larger regenerated CSA compared to those that received CCR2−/− BM. Intramuscular fat was increased at all time points compared to baseline. Thus, mice that lack CCR2 expression on BM‐derived cells have impaired muscle regeneration; macrophages are the likely cell type that mediates this outcome. Funding : Veterans Administration and NIH HL074236