Unloading during skeletal muscle regeneration retards iNOS-expressing macrophage recruitment and perturbs satellite cell accumulation

This study focused on macrophages expressing inducible nitric oxide synthase (iNOS) that synthesize nitric oxide, a key regulator of muscle regeneration, and compared the continuous hindlimb unloading (HU) by tail suspensionversus weight-bearing (WB) after skeletal muscle crush injury in rats. We found that in the WB group, the recruitment of iNOS+ proinflammatory macrophages into the injured site gradually increased until their peak number at 48  h post-injury. In the HU group, the accumulation of iNOS+ macrophages until 48  h after injury was significantly less than that in the WB group and continued to increase at 72 h. In accordance with attenuated and/or delayed iNOS+ macrophage recruitment, whole iNOS expression at 24 and 48  h after injury was weakened by unloading. Additionally, in the HU group, satellite cell content of dystrophin-positive non-injured areas diminished at 48 h after injury, and the numbers of activated satellite cells within the regenerating area at 72 and 96 h post-injury were significantly smalle r than those in the WB group. These findings suggest that muscle regeneration under unloading conditions results in attenuated and/or delayed recruitment of iNOS+ macrophages and lower iNOS expression in the early phase after muscle injury, leading to perturbed satellite cell accumulation and muscle regeneration.
Source: Histochemistry and Cell Biology - Category: Biomedical Science Source Type: research