The Ca2+-regulated protein and damage-associated molecular pattern, S100B, is promptly released by muscle tissue upon acute injury and contributes to the expansion of muscle precursor cells during the early phase of muscle regeneration by binding to RAGE and bFGF/FGFR1 on the myoblast surface [1]. However, during the late phase of muscle regeneration extracellular S100B levels diminish concomitant with myoblast terminal differentiation, suggesting that appropriate phase-specific levels of extracellular S100B are required for correct muscle regeneration [2]. To assess this point, we induced muscle injury in the Tibialis anterior muscle of C57Bl/6 mice and subsequently inoculated the damaged muscle with non-immune IgG or an S100B neutralizing antibody during the first days of regeneration. We found that sequestering extracellular S100B up to post-injury day 3 resulted in impaired muscle regeneration characterized by a dramatic reduction of the number of infiltrated macrophages, which resulted prevalently in the M1 activation state compared with IgG-injected muscles, and a reduction of the number of proliferating and differentiating satellite cells. I.p. injection of anti-S100B antibody gave similar results to local injection. Similar experiments performed in Rage-/- mice suggested that the effects of S100B were RAGE-dependent. However, repeated i.m. injections of S100B during the regenerative process translated into a significant increase in the recruitment of overstaying macrophages and impaired regeneration, suggesting that S100B may act as a chemoattractant for macrophages, as supported by in vitro experiments. Because we found higher levels of released S100B in muscles of dystrophic (mdx) mice compared with WT mice, our data suggest that appropriate levels of extracellular S100B are required at specific phases of muscle regeneration for efficient regeneration, and that chronic release of S100B in muscular dystrophy might concur to the disease. [1] Riuzzi & Sorci et al. (2011) J Cell Sci 124:2389-400; [2] Riuzzi & Sorci et al. (2012) PLoS ONE 7(1): e28700.
Appropriate levels of extracellular S100B protein in injured muscle are required for correct muscle regeneration.
RIUZZI, Francesca;BECCAFICO, SARA;SORCI, Guglielmo;DONATO, Rosario Francesco
2012
Abstract
The Ca2+-regulated protein and damage-associated molecular pattern, S100B, is promptly released by muscle tissue upon acute injury and contributes to the expansion of muscle precursor cells during the early phase of muscle regeneration by binding to RAGE and bFGF/FGFR1 on the myoblast surface [1]. However, during the late phase of muscle regeneration extracellular S100B levels diminish concomitant with myoblast terminal differentiation, suggesting that appropriate phase-specific levels of extracellular S100B are required for correct muscle regeneration [2]. To assess this point, we induced muscle injury in the Tibialis anterior muscle of C57Bl/6 mice and subsequently inoculated the damaged muscle with non-immune IgG or an S100B neutralizing antibody during the first days of regeneration. We found that sequestering extracellular S100B up to post-injury day 3 resulted in impaired muscle regeneration characterized by a dramatic reduction of the number of infiltrated macrophages, which resulted prevalently in the M1 activation state compared with IgG-injected muscles, and a reduction of the number of proliferating and differentiating satellite cells. I.p. injection of anti-S100B antibody gave similar results to local injection. Similar experiments performed in Rage-/- mice suggested that the effects of S100B were RAGE-dependent. However, repeated i.m. injections of S100B during the regenerative process translated into a significant increase in the recruitment of overstaying macrophages and impaired regeneration, suggesting that S100B may act as a chemoattractant for macrophages, as supported by in vitro experiments. Because we found higher levels of released S100B in muscles of dystrophic (mdx) mice compared with WT mice, our data suggest that appropriate levels of extracellular S100B are required at specific phases of muscle regeneration for efficient regeneration, and that chronic release of S100B in muscular dystrophy might concur to the disease. [1] Riuzzi & Sorci et al. (2011) J Cell Sci 124:2389-400; [2] Riuzzi & Sorci et al. (2012) PLoS ONE 7(1): e28700.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
