Basic fibroblast growth factor promotes in vivo muscle regeneration in murine muscular dystrophy

Abstract

Due to the lack of dystrophin, a subsarcolemmal protein, mdx mutant mice undergo spontaneous rounds of myofiber necrosisregeneration from the age of weaning. Muscle regeneration is likely to be controlled by basic fibroblast growth factor (bFGF) which is detectable in regenerating areas of mdx muscles. Moreover, the proliferation of mdx satellite cells seems to be particularly sensitive to bFGF in culture. We injected various concentrations of bFGF in the tibialis anterior muscle of 4-week-old mice at the time of the first round of muscle necrosis-regeneration, and we evaluated the in vivo effects of bFGF on mdx muscle regeneration by quantitative histology. Seven days after bFGF injection, the number of regenerated myofibers was significantly increased proportionally to the injected bFGF concentration. This effect was due to an enhanced replication of muscle satellite cells as shown by labeling the proliferating cells with 5-bromo-2′-deoxyuridine (BrdU). These results may provide a possibility of improving dystrophin-deficient muscle regeneration by increasing the availability of bFGF.