Comparison of the muscle fiber diameter and satellite cell frequency in human muscle biopsies.

Abstract

Satellite cells are responsible for the formation of postnatal muscle fibers. The number, mitotic activity, and differentiation potential of satellite cells and the muscle fiber diameter are tightly regulated events in normal muscle. The signal that induces satellite cells to stop proliferation once the determined muscle fiber size has been reached in normal growth is not known. The aim of the present study was to determine whether a correlation exists between satellite cell frequency and muscle fiber diameter in human muscle disease. Muscle biopsies from 7 cases of Duchenne muscular dystrophy (DMD), 8 other muscular dystrophies, 23 cases of inflammatory myopathy, and 22 cases of neurogenic atrophy were examined. The satellite cell number was elevated in DMD and neurogenic atrophy but not in other muscular dystrophies or inflammatory myopathies. Nevertheless, in all the diseased muscles, but not in normal controls, there was a significantly higher relative frequency of satellite cells with increasing fiber diameter. It has been shown before that satellite cells show ultrastructural and autoradiographic signs of activation and proliferation in myopathic and neurogenic conditions. We assume that we are dealing with activated, not quiescent, satellite cells in diseased muscle and that under these conditions the fiber diameter does not represent a stop signal for satellite cells to proliferate. The data suggest that not only the number of satellite cells matters in diseased muscle, as has been shown before, but that it is their behavior that influences, at least in part, progress and severity of muscle diseases.