Versican processing by a disintegrin-like and metalloproteinase domain with thrombospondin-1 repeats proteinases-5 and -15 facilitates myoblast fusion

Stupka, Nicole, Kintakas, Christopher, White, Jason D., Fraser, Fiona W., Hanciu, Michael, Aramaki-Hattori, Noriko, Martin, Sheree, Coles, Chantal, Collier, Fiona, Ward, Alister C., Apte, Suneel S. and McCulloch, Daniel R. 2013, Versican processing by a disintegrin-like and metalloproteinase domain with thrombospondin-1 repeats proteinases-5 and -15 facilitates myoblast fusion, Journal of biological chemistry, vol. 288, no. 3, pp. 1907-1917.

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Title Versican processing by a disintegrin-like and metalloproteinase domain with thrombospondin-1 repeats proteinases-5 and -15 facilitates myoblast fusion
Author(s) Stupka, Nicole
Kintakas, Christopher
White, Jason D.
Fraser, Fiona W.
Hanciu, Michael
Aramaki-Hattori, Noriko
Martin, Sheree
Coles, Chantal
Collier, Fiona
Ward, Alister C.
Apte, Suneel S.
McCulloch, Daniel R.
Journal name Journal of biological chemistry
Volume number 288
Issue number 3
Start page 1907
End page 1917
Total pages 11
Publisher American Society for Biochemistry and Molecular Biology
Place of publication Bethesda, Maryland
Publication date 2013-01
ISSN 0021-9258
Keyword(s) development
extracellular matrix
muscle regeneration
proteoglycan
skeletal muscle
ADAMITS
myoblast
versican
Summary Skeletal muscle development and regeneration requires the fusion of myoblasts into multinucleated myotubes. Because the enzymatic proteolysis of a hyaluronan and versican-rich matrix by ADAMTS versicanases is required for developmental morphogenesis, we hypothesized that the clearance of versican may facilitate the fusion of myoblasts during myogenesis. Here, we used transgenic mice and an in vitro model of myoblast fusion, C2C12 cells, to determine a potential role for ADAMTS versicanases. Versican processing was observed during in vivo myogenesis at the time when myoblasts were fusing to form multinucleated myotubes. Relevant ADAMTS genes, chief among them Adamts5 and Adamts15, were expressed both in developing embryonic muscle and differentiating C2C12 cells. Reducing the levels of Adamts5 mRNA in vitro impaired myoblast fusion, which could be rescued with catalytically active but not the inactive forms of ADAMTS5 or ADAMTS15. The addition of inactive ADAMTS5, ADAMTS15, or full-length V1 versican effectively impaired myoblast fusion. Finally, the expansion of a hyaluronan and versican-rich matrix was observed upon reducing the levels of Adamts5 mRNA in myoblasts. These data indicate that these ADAMTS proteinases contribute to the formation of multinucleated myotubes such as is necessary for both skeletal muscle development and during regeneration, by remodeling a versican-rich pericellular matrix of myoblasts. Our study identifies a possible pathway to target for the improvement of myogenesis in a plethora of diseases including cancer cachexia, sarcopenia, and muscular dystrophy.
Language eng
Field of Research 060107 Enzymes
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2013, American Society for Biochemistry and Molecular Biology
Persistent URL http://hdl.handle.net/10536/DRO/DU:30059489

Document type: Journal Article
Collection: School of Medicine
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