Cyclic mechanical strain inhibits skeletal myogenesis through activation of focal adhesion kinase, Rac‐1 GTPase, andNF‐kBtranscription factor

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Abstract
Myogenesis is a multistep developmental program that generates and regenerates skeletal muscles. Several extracellular factors have been identified that participate in the regulation of myogenesis. Although skeletal muscles are always subjected to mechanical stress in vivo, the role of mechanical forces in the regulation of myogenesis remains unknown. We have investigated the molecular mechanisms by which cyclic mechanical strain modulates myogenesis. Application of cyclic mechanical strain using the computer-controlled Flexcell Strain Unit increased the proliferation of C2C12 cells and inhibited their differentiation into myotubes. Cyclic strain increased the activity of cyclin-dependent kinase 2 (cdk2) and the cellular level of cyclin A, and inhibited the expression of myosin heavy chain and formation of myotubes in C2C12 cultures. The activity of nuclear factor-kappa B (NF-κB) transcription factor and the expression of NF-κB-regulated genes, cyclin D1 and IL-6, were augmented in response to mechanical ...
Funding Information
  • National Institutes of Health (HL63134)