Exosomes Derived From Mesenchymal Stem Cells Regulating Myotube Cell Atrophy via NF-κB Signaling Pathway.

Abstract

Bone marrow mesenchymal stem cells (BMSCs), with their potential for multidifferentiation and self-replication, are considered effective for repairing damaged tissues. BMSCs can repair and replace damaged tissues by differentiating into effective cells and secreting some cytokines that inhibit inflammation and promote tissue repair. Recent studies suggest that BMSCs' main role in tissue repair may involve the secretion of exosomes (BMSC-Exos). Basic research has shown that exosomes can have significant effects on orthopedic diseases such as osteoarthritis, muscle tissue injury, and fractures by stimulating regeneration and reducing inflammation. However, the effect of exosomes on tumor necrosis factor (TNF-α)-induced muscle atrophy remains unclear. Therefore, this study investigated the mechanism underlying the protective effect of BMSC-Exos on TNF-α-induced C2C12 myotube atrophy. Treatment with TNF-α (20 ng/mL) for 48 h significantly reduced myotube viability and diameter, which were subsequently reversed by treatment with BMSC-Exos. BMSC-Exos treatment suppressed the expression of E3 ubiquitin ligases, including Atrogin‑1/muscle atrophy F‑box and muscle ring‑finger protein‑1 (MuRF-1). Furthermore, it increased the protein expression levels of myoblast determination protein-1 (MyoD) in TNF-α-induced myotubes. BMSC-Exos also decreased the nuclear translocation of nuclear factor-κB (NF-κB) by inhibiting the phosphorylation of κB inhibitors. These findings indicate that BMSC-Exos may protect against TNF-α-induced myotube atrophy by inhibiting the proinflammatory NF-κB pathway.