Role of Ascorbic Acid in Skeletal Muscle Regeneration

Abstract

Total amount of L‐ascorbic acid (AsA) in human skeletal muscle is approximately 40%. As satellite cells, muscle specific stem cells, are responsible for providing new myoblast cells during the muscle regeneration process. Myoblast cells construct myofibers in the regenerative process including proliferation and differentiation. AsA is known to prevent scurvy helping dioxygenases for the prolines hydroxylation in collagen. It has been reported that AsA accelerated Ten‐Eleven Translocation (Tet) methylcytosine dioxygenase‐mediated generation of 5‐hydroxymethylcytosine (5hmc) from 5‐methylcytosine. We have previously reported that AsA deficiency causes skeletal muscle atrophy and deterioration in physical performance in senescence marker protein 30 knockout (SMP30‐KO) mice. In this study, we showed that AsA deficiency causes a delay of skeletal muscle regeneration in SMP30‐KO mouse which is unable to biosynthesis of AsA. Moreover, AsA administration after skeletal muscle injury recovered it regeneration. In vitro experiment, AsA treated C2C12 mouse myoblast cells showed higher cell proliferation rate, mRNA expression levels of myogenic differentiation markers such as myogenin and myomaker, and fusion index compared to untreated cells. Finally, we examine the 5hmc levels in AsA‐treated and untreated C2C12 cells. The 5hmc levels was higher in AsA‐treated cells than untreated cells. These results suggest that AsA induced skeletal muscle regeneration by enhancing the myoblast proliferation, differentiation, and DNA demethylation.Support or Funding InformationGrant‐in‐Aid for Early‐Career Scientists. Funding Agency: Japan Society for the Promotion of Science. Project number: 19K19822