| RRC ID |
44068
|
| Author |
Mikami T, Koyama S, Yabuta Y, Kitagawa H.
|
| Title |
Chondroitin sulfate is a crucial determinant for skeletal muscle development/regeneration and improvement of muscular dystrophies.
|
| Journal |
J Biol Chem
|
| Abstract |
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.
|
| Volume |
287(46)
|
| Pages |
38531-42
|
| Published |
2012-11-9
|
| DOI |
10.1074/jbc.M111.336925
|
| PII |
S0021-9258(20)62319-5
|
| PMID |
23007393
|
| PMC |
PMC3493898
|
| MeSH |
Animals
Cardiotoxins / metabolism
Cell Differentiation
Cells, Cultured
Chondroitin Sulfates / chemistry
Chondroitin Sulfates / physiology*
Gene Expression Regulation*
Glycosaminoglycans / metabolism
Hyaluronic Acid / chemistry
Hyaluronoglucosaminidase / metabolism*
Mice
Mice, Inbred C57BL
Mice, Inbred mdx
Muscle Development
Muscle, Skeletal / metabolism*
Muscular Dystrophies / physiopathology*
Muscular Dystrophies / therapy
Proteoglycans / metabolism
Regeneration
Time Factors
|
| IF |
4.238
|
| Times Cited |
18
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
C2C12(RCB0987) |
