Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710054, China.
Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710054, China; Department of Biomedical Engineering, Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor MI 48109-1078, USA; Department of Materials Science and Engineering, University of Michigan, Ann Arbor MI 48109-1078, USA.
Biomaterials. 2018 Aug;175:19-29. doi: 10.1016/j.biomaterials.2018.05.027. Epub 2018 May 18.
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.
在严重创伤的情况下，成肌细胞的再生过程受到抑制，形成纤维状瘢痕组织。了解生物活性纳米材料与成肌细胞之间的相互作用，可能对增强骨骼肌组织再生具有重要影响。在此，我们研究了单分散金和金银纳米颗粒（AuNPs 和 Au-AgNPs）对成肌细胞（C2C12）增殖、成肌分化的影响及其相关分子机制，以及在体内骨骼肌组织再生中的作用。结果表明，AuNPs 和 Au-AgNPs 可以支持成肌细胞的附着和增殖，且细胞毒性可忽略不计。在各种孵育条件（正常和分化培养基）下，AuNPs 和 Au-AgNPs 通过上调肌球蛋白重链（MHC）蛋白和成肌基因（MyoD、MyoG 和 Tnnt-1）的表达，显著增强了成肌细胞的成肌分化。进一步的分析表明，AuNPs 和 Au-AgNPs 可以激活丝裂原活化蛋白激酶 p38α 通路（p38α MAPK）信号通路，从而增强成肌分化。此外，AuNPs 和 Au-AgNPs 显著促进了大鼠前胫骨肌缺损模型中的体内骨骼肌再生。该研究可能为改善骨骼肌修复和再生提供了一种基于纳米材料的策略。
