S100B, a Ca2+-binding protein of the EF-hand type that exerts both intracellular and extracellular regulatory activities (1), is expressed in mature skeletal myofibers (2). Extracellular S100B modulates myoblast differentiation by interfering with the activation of p38 MAPK, thereby inhibiting the expression of myogenin (3), a muscle-specific transcription factor essential for myogenesis. S100B also stimulates the proliferation of myoblasts and reduces their apoptosis (4). Thus, S100B might contribute to embryonic myogenesis and skeletal muscle regeneration by activating myoblasts and satellite cells (SCs), respectively, and stimulating their proliferation. However, effects of S100B appear to be dependent on myoblast density, the S100B concentration and the duration of exposure of myoblasts to the protein as well as on the differential engagement of RAGE (receptor for advanced glycation end products) and bFGF receptor 1 (FGFR1) in low-density (LD) and high-density (HD) cultures, respectively (submitted for publication). The differential effects of S100B in LD and HD myoblasts are dependent on S100B/bFGF complex formation and S100B/bFGF engagement of FGFR1, in HD, but not LD myoblasts. S100B also binds to RAGE in HD myoblasts, but this interaction results in the blockade of RAGE signaling. By contrast, S100B only engages RAGE in LD myoblasts, the protein being unable to interact with FGFR1-bound bFGF in this condition. We addressed the question whether S100B might affect skeletal muscle tissue in vivo. We show here that: 1) damaged muscles release S100B; 2) S100B in crushed-muscle extract stimulates myoblast proliferation; 3) intramuscular injection of S100B results in activation of SCs in wild-type, but not RAGE-/- mice; 4) S100B accelerates the activation of quiescent primary myoblasts thereby stimulating their migration and proliferation; and 5) when administered for 24 h to LD myoblast/myotube cultures three days after their switch to differentiation medium, S100B rapidly stimulates the proliferation of non-fused, quiescent myoblasts such that after S100B removal more numerous and hypertrophic myotubes form during the next few days, compared to controls. Our data strongly support the possibility that S100B might physiologically participate in the muscle regeneration process by activating SCs and stimulating their migration and expansion, and that clearance of S100B results in enhanced myoblast differentiation. 1. Donato R et al (2008) Biochim Biophys Acta, DOI: 10.1016/j.bbamcr.2008.11.009; 2. Arcuri C et al (2002) Neuroscience 109:371-88; 3. Sorci G et al (2003) Mol Cell Biol 23:4870-81; 4. Riuzzi F et al (2006) J Cell Physiol 207:461-70.

S100B protein accelerates the activation of quiescent myoblasts and muscle satellite cells.

SORCI, Guglielmo;RIUZZI, Francesca;DONATO, Rosario Francesco
2009

Abstract

S100B, a Ca2+-binding protein of the EF-hand type that exerts both intracellular and extracellular regulatory activities (1), is expressed in mature skeletal myofibers (2). Extracellular S100B modulates myoblast differentiation by interfering with the activation of p38 MAPK, thereby inhibiting the expression of myogenin (3), a muscle-specific transcription factor essential for myogenesis. S100B also stimulates the proliferation of myoblasts and reduces their apoptosis (4). Thus, S100B might contribute to embryonic myogenesis and skeletal muscle regeneration by activating myoblasts and satellite cells (SCs), respectively, and stimulating their proliferation. However, effects of S100B appear to be dependent on myoblast density, the S100B concentration and the duration of exposure of myoblasts to the protein as well as on the differential engagement of RAGE (receptor for advanced glycation end products) and bFGF receptor 1 (FGFR1) in low-density (LD) and high-density (HD) cultures, respectively (submitted for publication). The differential effects of S100B in LD and HD myoblasts are dependent on S100B/bFGF complex formation and S100B/bFGF engagement of FGFR1, in HD, but not LD myoblasts. S100B also binds to RAGE in HD myoblasts, but this interaction results in the blockade of RAGE signaling. By contrast, S100B only engages RAGE in LD myoblasts, the protein being unable to interact with FGFR1-bound bFGF in this condition. We addressed the question whether S100B might affect skeletal muscle tissue in vivo. We show here that: 1) damaged muscles release S100B; 2) S100B in crushed-muscle extract stimulates myoblast proliferation; 3) intramuscular injection of S100B results in activation of SCs in wild-type, but not RAGE-/- mice; 4) S100B accelerates the activation of quiescent primary myoblasts thereby stimulating their migration and proliferation; and 5) when administered for 24 h to LD myoblast/myotube cultures three days after their switch to differentiation medium, S100B rapidly stimulates the proliferation of non-fused, quiescent myoblasts such that after S100B removal more numerous and hypertrophic myotubes form during the next few days, compared to controls. Our data strongly support the possibility that S100B might physiologically participate in the muscle regeneration process by activating SCs and stimulating their migration and expansion, and that clearance of S100B results in enhanced myoblast differentiation. 1. Donato R et al (2008) Biochim Biophys Acta, DOI: 10.1016/j.bbamcr.2008.11.009; 2. Arcuri C et al (2002) Neuroscience 109:371-88; 3. Sorci G et al (2003) Mol Cell Biol 23:4870-81; 4. Riuzzi F et al (2006) J Cell Physiol 207:461-70.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11391/41540
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact