Methylsulfonylmethane (MSM) Treatment Enhances C2C12 Wound Closure and Protects Cells from Oxidative Stress

Abstract

MSM is known to provide anti‐inflammatory and anti‐oxidant effects in both animals and humans. Because both exercise and chronic disease have the potential to induce inflammation and oxidative stress in skeletal muscle, MSM may be a novel therapy to counter the negative consequences of these stressors on skeletal muscle function. Recent evidence has shown that MSM supplementation in human subjects can increase serum MSM concentrations to 2–3 mM. These serum concentrations of MSM have been associated with reduced muscle pain and reduced markers of muscle damage (creatine kinase) following damaging exercise. Therefore, MSM may protect muscle against damage or favorably influence the adaptive capacity of skeletal muscle under stress. However, it is not known if MSM induces this protection by directly acting on skeletal muscle. Therefore, our objective was to determine if MSM may provide cytoprotection from oxidative stress, or enhance the recovery processes in C2C12 myoblasts. We found that treating C2C12 myoblasts with increasing concentrations of MSM (0–200 mM) for 24, 48 and 72 hours decreased cell metabolism (via Alamar Blue) at high concentrations (100 & 200 mM); however this decline was not associated with increased cell death (via Trypan Blue). Flow cytometry analysis showed MSM treatment (200 mM) trapped myoblasts in G1 phase (+51%) and reduced the number of cells moving into S phase (DNA synthesis; −38%) or G2+M phase(mitosis; −43%) of cell division. MSM had no effect on C2C12 differentiation (d1, d4, d6). High concentrations of MSM (100 & 200 mM) were able to reduce cell death (−36% & −89% respectively) induced by oxidative stress (tert‐butyl hydrogen peroxide; 20 uM). Because heat shock proteins (HSPs) are known to be cytoprotective, we determined if increasing concentrations of MSM induced HSP expression; however, we found no changes in HSP70 and HSP27 expression. Lastly, lower concentrations (12.5 mM) of MSM enhanced wound closure (+35%) from a scratch assay 24 following treatment, while higher concentrations (200 mM) were associated with an impaired closure rate (−51%). While more applied research is needed, these findings suggest that MSM may directly alter the skeletal muscle response to stress and injury. Therefore, MSM supplementation may serve as an ergogenic aide to protect skeletal muscle from injury.Support or Funding InformationFunded by Bergstrom Nutrition to CDT