title: Chondroitin sulfate is a crucial determinant for skeletal muscle development/regeneration and improvement of muscular dystrophies.
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.
authors.affiliation: Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan.
authors.forename: Tadahisa
authors.initials: T
authors.lastname: Mikami
authors.forename: Shinji
authors.initials: S
authors.lastname: Koyama
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yabuta
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitagawa
mesh_terms: D000818:Animals; D054715:Cardiotoxins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000502:physiology*; D005786:Gene Expression Regulation; D006025:Glycosaminoglycans / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry; D006821:Hyaluronoglucosaminidase / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000378:metabolism*; D009136:Muscular Dystrophies / Q000503:physiopathology* / Q000628:therapy; D011509:Proteoglycans / Q000378:metabolism; D012038:Regeneration; D013997:Time Factors
chemical_list: D054715:Cardiotoxins; D006025:Glycosaminoglycans; D011509:Proteoglycans; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; C469220:Hyal1 protein, mouse; D006821:Hyaluronoglucosaminidase