The inflammatory response, a mixed blessing for muscle homeostasis and plasticity

Skeletal muscle makes up almost half the body weight of heathy individuals and is involved in several vital functions, including breathing, thermogenesis, metabolism, and locomotion. Skeletal muscle exhibits enormous plasticity with its capacity to adapt to stimuli such as changes in mechanical loading, nutritional interventions, or environmental factors (oxidative stress, inflammation, and endocrine changes). Satellite cells and timely recruited inflammatory cells are key actors in muscle homeostasis, injury, and repair processes. Conversely, uncontrolled recruitment of inflammatory cells or chronic inflammatory processes leads to muscle atrophy, fibrosis and, ultimately, impairment of muscle function. Muscle atrophy and loss of function are reported to occur either in physiological situations such as aging, cast immobilization, and prolonged bed rest, as well as in many pathological situations, including cancers, muscular dystrophies, and several other chronic illnesses. In this review, we highlight recent discoveries with respect to the molecular mechanisms leading to muscle atrophy caused by modified mechanical loading, aging, and diseases. We also summarize current perspectives suggesting that the inflammatory process in muscle homeostasis and repair is a double-edged sword. Lastly, we review recent therapeutic approaches for treating muscle wasting disorders, with a focus on the RANK/RANKL/OPG pathway and its involvement in muscle inflammation, protection and regeneration processes.

Automated summary

Skeletal muscle, comprising almost half of the body weight, plays vital roles in various functions. It has high plasticity and can adapt to stimuli. Satellite cells and inflammatory cells have important roles in muscle homeostasis, injury, and repair processes. However, uncontrolled recruitment of inflammatory cells or chronic inflammation can lead to muscle atrophy and impairment of function. Muscle atrophy and loss of function occur in both physiological and pathological situations. Recent studies have revealed the molecular mechanisms responsible for muscle atrophy caused by modified mechanical loading, aging, and diseases. The inflammatory process in muscle homeostasis and repair is found to be a double-edged sword. Recent therapeutic approaches for muscle wasting disorders, particularly focusing on the RANK/RANKL/OPG pathway, have been reviewed.