Polydeoxyribonucleotide attenuates dexamethasone-induced skeletal muscle atrophy by suppressing oxidative stress and regulating muscle protein turnover
TL;DR
Collectively, PDRN attenuated DEX-induced skeletal muscle atrophy by suppressing oxidative stress and regulating muscle protein turnover, suggesting its potential as a therapeutic strategy for glucocorticoid-induced muscle wasting.
Abstract
Glucocorticoid-induced muscle atrophy is characterized by excessive oxidative stress and disrupted muscle protein homeostasis. Polydeoxyribonucleotide (PDRN) exerts tissue-protective and regenerative effects; however, its therapeutic potential in muscle atrophy remains unclear. This study investigated the protective effects of PDRN against dexamethasone (DEX)-induced muscle atrophy in vitro and in vivo. Differentiated C2C12 myotubes were treated with PDRN in the presence or absence of DEX (100 µM). PDRN showed no cytotoxicity, and concentrations of 10, 25, and 50 µg/mL were selected for subsequent experiments. PDRN significantly attenuated DEX-induced myotube thinning and reduced intracellular reactive oxygen species. For in vivo evaluation, C57BL/6 mice received DEX (25 mg/kg/day) for 14 days with or without intramuscular PDRN administration. PDRN treatment improved treadmill performance and preserved GCM mass compared with DEX-treated mice. Histological analyses demonstrated significant increases in muscle fiber area and minimum Feret diameter following PDRN treatment. Furthermore, PDRN reduced oxidative damage, as evidenced by decreased 4-hydroxynonenal staining and malondialdehyde levels while restoring glutathione content. PDRN also upregulated nuclear factor erythroid 2-related factor 2 signaling and normalized antioxidant-related gene expression. In addition, PDRN enhanced expression of anabolic markers, including insulin-like growth factor-1, myogenic differentiation 1, and myogenin while suppressing the atrophy-related factors muscle RING finger-1 and Atrogin-1. These changes were accompanied by increased MHC expression and activation of the mTOR/S6K pathway, together with suppression of the myostatin/Smad/FoxO3a signaling pathway. Collectively, PDRN attenuated DEX-induced skeletal muscle atrophy by suppressing oxidative stress and regulating muscle protein turnover, suggesting its potential as a therapeutic strategy for glucocorticoid-induced muscle wasting.