Gold and gold-silver alloy nanoparticles enhance the myogenic differentiation of myoblasts through p38 MAPK signaling pathway and promote in vivo skeletal muscle regeneration

Abstract

Under the severe trauma condition, the skeletal muscles regeneration process is inhibited by forming fibrous scar tissues. Understanding the interaction between bioactive nanomaterials and myoblasts perhaps has important effect on the enhanced skeletal muscle tissue regeneration. Herein, we investigate the effect of monodispersed gold and gold-silver nanoparticles (AuNPs and Au-AgNPs) on the proliferation, myogenic differentiation and associated molecular mechanism of myoblasts (C2C12), as well as the in vivo skeletal muscle tissue regeneration. Our results showed that AuNPs and Au-AgNPs could support myoblast attachment and proliferation with negligible cytotoxicity. Under various incubation conditions (normal and differentiation medium), AuNPs and Au-AuNPs significantly enhanced the myogenic differentiation of myoblasts by upregulating the expressions of myosin heavy chain (MHC) protein and myogenic genes (MyoD, MyoG and Tnnt-1). The further analysis demonstrated that AuNPs and Au-AgNPs could activate the p38α mitogen-activated protein kinase pathway (p38α MAPK) signaling pathway and enhance the myogenic differentiation. Additionally, the AuNPs and Au-AgNPs significantly promote the in vivo skeletal muscle regeneration in a tibialis anterior muscle defect model of rat. This study may provide a nanomaterials-based strategy to improve the skeletal muscle repair and regeneration.

Keywords: Au and Au-Ag nanoparticles; Molecular mechanism; Myoblasts; Myogenic differentiation; Skeletal muscle regeneration.