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Glucocorticoids improve myogenic differentiation in vitro by suppressing the synthesis of versican, a transitional matrix protein overexpressed in dystrophic skeletal muscles

McRae, Natasha, Forgan, Leonard, McNeill, Bryony, Addinsall, Alex, McCulloch, Daniel, Van der Poel, Chris and Stupka, Nicole 2017, Glucocorticoids improve myogenic differentiation in vitro by suppressing the synthesis of versican, a transitional matrix protein overexpressed in dystrophic skeletal muscles, International journal of molecular sciences, vol. 18, no. 12, pp. 1-22, doi: 10.3390/ijms18122629.

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Title Glucocorticoids improve myogenic differentiation in vitro by suppressing the synthesis of versican, a transitional matrix protein overexpressed in dystrophic skeletal muscles
Author(s) McRae, Natasha
Forgan, Leonard
McNeill, BryonyORCID iD for McNeill, Bryony orcid.org/0000-0002-1580-2925
Addinsall, Alex
McCulloch, Daniel
Van der Poel, Chris
Stupka, NicoleORCID iD for Stupka, Nicole orcid.org/0000-0002-1000-1707
Journal name International journal of molecular sciences
Volume number 18
Issue number 12
Article ID 2629
Start page 1
End page 22
Total pages 22
Publisher MDPI
Place of publication Basel, Switzerland
Publication date 2017-12
ISSN 1422-0067
Keyword(s) Duchenne muscular dystrophy
fibrosis
glucocorticoids
mdx mouse
myogenesis
versican
Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Biochemistry & Molecular Biology
Chemistry, Multidisciplinary
Chemistry
Duchenne Muscular-Dystrophy
Chondroitin Sulfate/Dermatan sulfate
Myoblast fusion
MDX mice
Extracellular-Matrix
Metalloproteinase domain
Fibroblast proteoglycan
Disintegrin-like
TGF-Beta
Expression
Summary In Duchenne muscular dystrophy (DMD), a dysregulated extracellular matrix (ECM) directly exacerbates pathology. Glucocorticoids are beneficial therapeutics in DMD, and have pleiotropic effects on the composition and processing of ECM proteins in other biological contexts. The synthesis and remodelling of a transitional versican-rich matrix is necessary for myogenesis; whether glucocorticoids modulate this transitional matrix is not known. Here, versican expression and processing were examined in hindlimb and diaphragm muscles from mdx dystrophin-deficient mice and C57BL/10 wild type mice. V0/V1 versican (Vcan) mRNA transcripts and protein levels were upregulated in dystrophic compared to wild type muscles, especially in the more severely affected mdx diaphragm. Processed versican (versikine) was detected in wild type and dystrophic muscles, and immunoreactivity was highly associated with newly regenerated myofibres. Glucocorticoids enhanced C2C12 myoblast fusion by modulating the expression of genes regulating transitional matrix synthesis and processing. Specifically, Tgfβ1, Vcan and hyaluronan synthase-2 (Has2) mRNA transcripts were decreased by 50% and Adamts1 mRNA transcripts were increased three-fold by glucocorticoid treatment. The addition of exogenous versican impaired myoblast fusion, whilst glucocorticoids alleviated this inhibition in fusion. In dystrophic mdx muscles, versican upregulation correlated with pathology. We propose that versican is a novel and relevant target gene in DMD, given its suppression by glucocorticoids and that in excess it impairs myoblast fusion, a process key for muscle regeneration.
Language eng
DOI 10.3390/ijms18122629
Field of Research 0399 Other Chemical Sciences
0604 Genetics
0699 Other Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2017, the authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30108676

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.