S100B protein activates quiescent myoblasts and muscle satellite cells.

Treatment of high-density myoblast cell lines or primary myoblasts (satellite cells) in differentiation medium (DM) with pM amounts of S100B results in inhibition of differentiation, stimulation of proliferation and inhibition of apoptosis (Mol Cell Biol 23:4870-4881; J Cell Physiol 207:461-470). Thus, S100B might participate in embryonic myogenesis and muscle regeneration by increasing the myoblast/satellite cell number and by modulating myotube/myofiber hypertrophy. S100B stimulated myotube formation when given to low-density myoblasts in DM for 24 h followed by a 72-h cultivation in the absence of S100B, and administration of S100B for 24h to myoblasts/myotubes that had been cultivated for 72 h in DM resulted in myotube hypertrophy. These latter results suggest that S100B might activate non-fused, quiescent (G0-arrested) myoblasts and stimulate their proliferation, thereby promoting myotube formation/hypertrophy. To support this possibility, we made myoblasts quiescent, switched them to DMEM for 16 h and analyzed them for cell cycle by FACS. S100B decreased the fraction of myoblasts in G0/G1 phase and increased the fraction of myoblasts in S phase. These events were accompanied by a rapid activation of ERK1/2, p38 MAPK and Akt, and in a typical time-course of changes in the levels of the muscle-specific transcription factors Myf5 and MyoD (J Cell Biol 142:1447- 1459). However, a long exposure (i.e., 3-4 days) of low-density myoblasts to S100B resulted in inhibition of differentiation, similar to a brief (24 h) exposure to S100B of high-density myoblasts (with stimulation of ERK1/2 and inhibition of p38 MAPK). The finding that S100B can activate quiescent myoblasts and satellite cells suggests that the protein might contribute to regulate embryonic myogenesis and muscle regeneration by stimulating proliferation of low-density myoblasts/satellite cells and by reducing the myogenic potential of high-density myoblasts/satellite cells by its proliferative stimulus. Analyses are in progress to dissect the molecular mechanism whereby S100B exerts such a dual role in myoblast differentiation. However, the finding that S100B can activate quiescent myoblasts and satellite cells suggests that the protein might contribute to regulate embryonic myogenesis and muscle regeneration, stimulating proliferation and migration of low-density myoblasts/satellite cells and reducing the myogenic potential of high-density myoblasts/satellite cells.