LAUSR

Timely and complete recovery of muscle mass and function following a bout of physical disuse are critical components of returning to normal activities of daily living and lifestyle. Proper cross talk between the muscle tissue and myeloid cells (e.g., macrophages) throughout the recovery period from disuse atrophy plays a significant role for complete resolution of muscle size and function. Chemokine C-C motif ligand 2 (CCL2) has a critical function of recruiting macrophages during the early phase of muscle damage. However, the importance of CCL2 has not been defined in the context of disuse and recovery; a physiologically relevant model of atrophy and regrowth. Here, we utilized a mouse model of whole-body CCL2 deletion (CCL2KO) and subjected them to a period of hindlimb unloading followed by reloading to investigate the importance of CCL2 on the regrowth of muscle following disuse atrophy using ex vivo muscle tests, immunohistochemistry and FACS approaches. We show mice that lack CCL2 display an incomplete recovery of muscle mass, myofiber cross-sectional area, and muscle function during the recovery from disuse atrophy. Mice that lack CCL2 have decreased skeletal muscle collagen turnover which may be related to defects in muscle function and stiffness. In addition, we show that the recruitment of macrophages to skeletal muscle is dramatically reduced in CCL2KO mice during the recovery from disuse atrophy, which likely precipitates poor recovery of muscle size and function and aberrant collagen remodeling.