Glucocorticoid Effects in Muscle Regeneration: Impact on Muscle Fibers, Fibro-Adipogenic Progenitors and Associated Implications for Bones

Myopathies are a diverse group of disorders primarily affecting skeletal muscles, resulting in muscle weakness, impaired function, and, in some cases, pain or muscle wasting. These conditions can be inherited, such as Duchenne Muscular Dystrophy (DMD), or acquired, including inflammatory and toxic myopathies. DMD, caused by mutations in the dystrophin gene, leads to progressive muscle degeneration, reduced mobility, and premature mortality. Inflammatory myopathies, such as dermatomyositis, involve immune-mediated damage to muscle fibers and can affect multiple organ systems. Glucocorticoids are widely used in the management of myopathies due to their anti-inflammatory properties, yet prolonged high-dose treatment can induce muscle atrophy and weakness. Understanding the cellular and molecular mechanisms underlying glucocorticoid effects on skeletal muscle is critical for optimizing therapeutic strategies and minimizing side effects. This study investigates the role of glucocorticoid signalling in muscle injury and regeneration using genetically modified mouse models. Fibro-adipogenic progenitors were purified from murine muscles, and muscle injury was induced using cardiotoxin. Muscle regeneration, enzyme activity, and lipid accumulation were analysed to assess the impact of glucocorticoid receptor modulation. These findings provide insights into the interactions between glucocorticoid signalling, muscle regeneration, and adipogenic differentiation, highlighting potential targets for improving muscle repair while limiting glucocorticoid-induced adverse effects. These results contribute to a better understanding of therapeutic approaches for myopathies and their long-term management.