Ionic Silicon Protects Oxidative Damage and Promotes Skeletal Muscle Cell Regeneration.

Kamal Awad,Neelam Ahuja,Zhiying Wang,Venu Varanasi,Sara Peper,Matthew Fiedler,Marco Brotto,Pranesh Aswath

doi:10.3390/ijms22020497

Kamal Awad, Neelam Ahuja + Show 6 more

Open Access

https://doi.org/10.3390/ijms22020497

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Abstract

Volumetric muscle loss injuries overwhelm the endogenous regenerative capacity of skeletal muscle, and the associated oxidative damage can delay regeneration and prolong recovery. This study aimed to investigate the effect of silicon-ions on C2C12 skeletal muscle cells under normal and excessive oxidative stress conditions to gain insights into its role on myogenesis during the early stages of muscle regeneration. In vitro studies indicated that 0.1 mM Si-ions into cell culture media significantly increased cell viability, proliferation, migration, and myotube formation compared to control. Additionally, MyoG, MyoD, Neurturin, and GABA expression were significantly increased with addition of 0.1, 0.5, and 1.0 mM of Si-ion for 1 and 5 days of C2C12 myoblast differentiation. Furthermore, 0.1–2.0 mM Si-ions attenuated the toxic effects of H2O2 within 24 h resulting in increased cell viability and differentiation. Addition of 1.0 mM of Si-ions significantly aid cell recovery and protected from the toxic effect of 0.4 mM H2O2 on cell migration. These results suggest that ionic silicon may have a potential effect in unfavorable situations where reactive oxygen species is predominant affecting cell viability, proliferation, migration, and differentiation. Furthermore, this study provides a guide for designing Si-containing biomaterials with desirable Si-ion release for skeletal muscle regeneration.

Highlights

Skeletal muscle constitutes about 40–50% of total body mass and is responsible for movement of the human body [1]
After 24 h, 0.1 mM of Si in growth medium (GM) significantly increased cell viability compared to the control (* p < 0.05, n = 3 per group) as indicated by the MTS-assay results, expressed as optical density (OD)
After confirming the positive effect of Si on myoblast functionalities, we studied its effect on C2C12 myoblasts under toxic oxidative stress conditions produced by H2 O2 as a source of reactive oxygen species (ROS)

Summary

Introduction

Skeletal muscle constitutes about 40–50% of total body mass and is responsible for movement of the human body [1]. Bioactive scaffolds and cell laden biomaterials [13,14,15] have been proposed to stimulate functional muscle regeneration These strategies aim to deliver the native ECM with the required cell types (stem or progenitor cells) and growth factors to the injury site, a key step in the regenerative process [16,17]. This process is initiated by the activation of satellite cells, or mononucleated muscle precursor cells, that undergo several proliferative cycles to differentiate to form multinucleated myotubes [18,19,20]. The expression of the myogenic marker MyoG is an early indicator of myoblast commitment and differentiation [18,22]

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