We reported that treatment of high-density myoblasts and satellite cells in differentiation medium (DM) with pM amounts of S100B caused inhibition of differentiation and apoptosis, and stimulation of proliferation. Thus, S100B might participate in embryonic myogenesis and muscle regeneration by increasing the myoblast/satellite cell number, and by modulating myotube and/or myofiber hypertrophy. We show that, when administered to low-density myoblasts for 24 h only S100B stimulates myotube formation (as measured 3 days after withdrawal of S100B), and administration (for 24 h) of S100B to low-density myoblasts 3 days after their switch to DM induces myotube hypertrophy. Because non-fused myoblasts in DM are quiescent, these results suggest that S100B might activate quiescent myoblasts. In fact, S100B decreases the fraction in G0/G1 phase and increases the fraction in S phase in myoblasts made quiescent, switched to DMEM for 16 h and analyzed for cell cycle. These changes, indicative of S100B having activated quiescent myoblasts and stimulated their proliferation, are accompanied by a rapid activation of ERK1/2, p38 MAPK and Akt, upregulation of M-cadherin and a time-course of changes in Myf-5 and MyoD levels typical of activated myoblasts. Thus, the final S100B effect on differentiation varies depending on the duration of exposure of myoblasts to S100B and on myoblast density: a long exposure (i.e., 3-4 days) causes inhibition of differentiation irrespective of myoblast density as does a brief (24 h) exposure of high-density myoblasts (with ERK1/2 stimulation, p38 MAPK inactivation and M-cadherin downregulation), as opposed to stimulation of differentiation in the case of a brief exposure of low-density myoblasts (which show activated ERK1/2 and p38 MAPK and upregulated M-cadherin). Thus, both the extent of cell-cell contacts and the duration of exposure condition the sensitivity of myoblasts to S100B, suggesting that S100B might play a dual regulatory role during embryonic myogenesis and muscle regeneration.

S100B activates quiescent myoblasts and satellite cells

RIUZZI, Francesca;SORCI, Guglielmo;DONATO, Rosario Francesco
2006

Abstract

We reported that treatment of high-density myoblasts and satellite cells in differentiation medium (DM) with pM amounts of S100B caused inhibition of differentiation and apoptosis, and stimulation of proliferation. Thus, S100B might participate in embryonic myogenesis and muscle regeneration by increasing the myoblast/satellite cell number, and by modulating myotube and/or myofiber hypertrophy. We show that, when administered to low-density myoblasts for 24 h only S100B stimulates myotube formation (as measured 3 days after withdrawal of S100B), and administration (for 24 h) of S100B to low-density myoblasts 3 days after their switch to DM induces myotube hypertrophy. Because non-fused myoblasts in DM are quiescent, these results suggest that S100B might activate quiescent myoblasts. In fact, S100B decreases the fraction in G0/G1 phase and increases the fraction in S phase in myoblasts made quiescent, switched to DMEM for 16 h and analyzed for cell cycle. These changes, indicative of S100B having activated quiescent myoblasts and stimulated their proliferation, are accompanied by a rapid activation of ERK1/2, p38 MAPK and Akt, upregulation of M-cadherin and a time-course of changes in Myf-5 and MyoD levels typical of activated myoblasts. Thus, the final S100B effect on differentiation varies depending on the duration of exposure of myoblasts to S100B and on myoblast density: a long exposure (i.e., 3-4 days) causes inhibition of differentiation irrespective of myoblast density as does a brief (24 h) exposure of high-density myoblasts (with ERK1/2 stimulation, p38 MAPK inactivation and M-cadherin downregulation), as opposed to stimulation of differentiation in the case of a brief exposure of low-density myoblasts (which show activated ERK1/2 and p38 MAPK and upregulated M-cadherin). Thus, both the extent of cell-cell contacts and the duration of exposure condition the sensitivity of myoblasts to S100B, suggesting that S100B might play a dual regulatory role during embryonic myogenesis and muscle regeneration.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11391/27510
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