The fate of proliferating cells in skeletal muscle after denervation or tenotomy: An autoradiographic study

Abstract

During the first 7 days after denervation or tenotomy of skeletal muscle there is increased cell proliferation, as measured autoradiographically by [ 3H]thymidine incorporation. By 21 days most of the labelled cells have disappeared. The present experiment was designed to measure residual levels of labelling in skeletal muscles at 21 days after denervation or tenotomy, when [ 3H]thymidine had been available for the first 7 days. This was to determine the fate of cells labelled at 7 days and to detect whether continued cell proliferation had occurred during the intervening period, as evidenced by the dilution of nuclear label. Tibialis anterior muscles of 16 mice were denervated, tenotomized or sham-operated, and the animals injected with a single daily pulse of [ 3H]thymidine for the first 7 days only. In denervated muscle the 11% of muscle nuclei and 41% of connective tissue nuclei labelled at 7 days had decreased to 2 and 13%, respectively, by 21 days. These values were still significantly higher than in 21 day controls (0.2 and 1.9%, respectively). In muscle nuclei (myonuclei and satellite cell nuclei) there was a significant decrease in the amount of label per nucleus. This was interpreted as evidence of continued cell proliferation. However, this did not produce an increase in numbers of muscle nuclei. It was concluded that: (1) there was turnover of satellite cells and possibly myonuclei, the latter probably through continued division and incorporation of satellite cells; and (2) the extra satellite cells and myonuclei produced were probably extruded from the fibre to the extracellular space. By 21 days after tenotomy the 4% of muscle nuclei and 23% of connective tissue nuclei labelled at 7 days had diminished to 21 day control levels (0.1 and 1.3%, respectively). It was concluded that the release of tension and inactivity in the muscle had stimulated cell proliferation during the first 7 days. However, this proliferative stimulus was not sustained probably because of maintenance of an intact innervation and also because tenotomy produced much less muscular atrophy than denervation.