INHIBITION OF PROLIFERATION IN 8-WEEK-OLD MDX-MOUSE MUSCLE FIBROBLASTS IN-VITRO

Our purpose is to understand why mdx muscle does not show the progress ive degeneration observed in human Duchenne muscular dystrophy (DMD) m uscle. In the mouse, the regenerative process compensates for the necr osis of the muscle fibers, particularly during the acute phase of the disease (5-9 weeks). In DMD muscle, there is a gradual failure of the regenerative process and the muscle fibers are replaced by connective and fatty tissue. We propose that distinct properties of mdx and DMD m uscle fibroblasts could be one of the reasons for the differences betw een the mdx and DMD phenotypes. We found that fibroblasts taken from h uman DMD and control muscle had similar in vitro proliferative capacit ies. The proliferation rate of mouse muscle fibroblasts decreased duri ng the acute phase of the disease, and inhibition was complete in fibr oblasts from 8-week-old mdx mice. Moreover, the medium conditioned by these cells inhibited fibroblast proliferation. The effect was specifi c for fibroblasts, since this conditioned medium stimulated myoblast p roliferation, as did control fibroblast-conditioned medium. These resu lts suggest that 8-week-old mdx mouse muscle fibroblasts produce an in hibitor of their own proliferation and a growth factor specific for m yoblasts in vitro. If these factors are secreted in vivo, the growth i nhibitory factor may stop fibroblast proliferation whereas the mitogen ic activity could stimulate satellite cell proliferation, thus favouri ng muscle regeneration.