| First Author | Mikami T | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 46 | Pages | 38531-42 |
| PubMed ID | 23007393 | Mgi Jnum | J:315921 |
| Mgi Id | MGI:6829125 | Doi | 10.1074/jbc.M111.336925 |
| Citation | Mikami T, et al. (2012) Chondroitin sulfate is a crucial determinant for skeletal muscle development/regeneration and improvement of muscular dystrophies. J Biol Chem 287(46):38531-42 |
| abstractText | Skeletal muscle formation and regeneration require myoblast fusion to form multinucleated myotubes or myofibers, yet their molecular regulation remains incompletely understood. We show here that the levels of extra- and/or pericellular chondroitin sulfate (CS) chains in differentiating C2C12 myoblast culture are dramatically diminished at the stage of extensive syncytial myotube formation. Forced down-regulation of CS, but not of hyaluronan, levels enhanced myogenic differentiation in vitro. This characteristic CS reduction seems to occur through a cell-autonomous mechanism that involves HYAL1, a known catabolic enzyme for hyaluronan and CS. In vivo injection of a bacterial CS-degrading enzyme boosted myofiber regeneration in a mouse cardiotoxin-induced injury model and ameliorated dystrophic pathology in mdx muscles. Our data suggest that the control of CS abundance is a promising new therapeutic approach for the treatment of skeletal muscle injury and progressive muscular dystrophies. |
