MECHANICAL LOAD INDUCES SARCOPLASMIC WOUNDING AND FGF RELEASE IN DIFFERENTIATED HUMAN SKELETAL-MUSCLE CULTURES

The transduction mechanism (or mechanisms) responsible for converting a mechanical load into a skeletal muscle growth response are unclear, In this study we have used a mechanically active tissue culture model of differentiated human skeletal muscle cells to investigate the relat ionship between mechanical load, sarcolemma wounding, fibroblast growt h factor release, and skeletal muscle cell growth, Using the Flexcell Strain Unit we demonstrate that as mechanical load increases, so too d oes the amount of sarcolemma wounding. A similar relationship was also observed between the level of mechanical load inflicted on the cells and the amount of bFGF (FGF2) released into the surrounding medium. In addition, we demonstrate that the muscle cell growth response induced by chronic mechanical loading in culture can be inhibited by the pres ence of an antibody capable of neutralizing the biological activity of FGF. This study provides direct evidence that mechanically induced, s arcolemma wound-mediated FGF release is an important autocrine mechani sm for transducing the stimulus of mechanical load into a skeletal mus cle growth response.