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Treatment of dystrophic mdx mice with an adamts-5 specific monoclonal antibody increases the ex vivo strength of isolated fast twitch hindlimb muscles

Addinsall, AB, Forgan, Leonard, McRae, NL, Kelly, RW, McDonald, PL, McNeil, B, McCulloch, DR and Stupka, Nicole 2020, Treatment of dystrophic mdx mice with an adamts-5 specific monoclonal antibody increases the ex vivo strength of isolated fast twitch hindlimb muscles, Biomolecules, vol. 10, no. 3, doi: 10.3390/biom10030416.

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Title Treatment of dystrophic mdx mice with an adamts-5 specific monoclonal antibody increases the ex vivo strength of isolated fast twitch hindlimb muscles
Author(s) Addinsall, AB
Forgan, LeonardORCID iD for Forgan, Leonard orcid.org/0000-0002-3276-8140
McRae, NL
Kelly, RW
McDonald, PL
McNeil, B
McCulloch, DR
Stupka, NicoleORCID iD for Stupka, Nicole orcid.org/0000-0002-1000-1707
Journal name Biomolecules
Volume number 10
Issue number 3
Article ID ARTN 416
Total pages 18
Publisher MDPI
Place of publication Switzerland
Publication date 2020-03-01
ISSN 2218-273X
2218-273X
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
ADAMTS-5
contractile function
desmin
Duchenne muscular dystrophy
mdx mouse
myogenesis
skeletal muscle
versican
versikine
METALLOPROTEINASE DOMAIN
EXTRACELLULAR-MATRIX
DISINTEGRIN-LIKE
SKELETAL-MUSCLE
IN-VIVO
EXPRESSION
CELL
REGENERATION
TURNOVER
Summary Aberrant extracellular matrix synthesis and remodeling contributes to muscle degeneration and weakness in Duchenne muscular dystrophy (DMD). ADAMTS-5, a secreted metalloproteinase with catalytic activity against versican, is implicated in myogenesis and inflammation. Here, using the mdx mouse model of DMD, we report increased ADAMTS-5 expression in dystrophic hindlimb muscles, localized to regions of regeneration and inflammation. To investigate the pathophysiological significance of this, 4-week-old mdx mice were treated with an ADAMTS-5 monoclonal antibody (mAb) or IgG2c (IgG) isotype control for 3 weeks. ADAMTS-5 mAb treatment did not reduce versican processing, as protein levels of the cleaved versikine fragment did not differ between hindlimb muscles from ADAMTS-5 mAb or IgG treated mdx mice. Nonetheless, ADAMTS-5 blockade improved ex vivo strength of isolated fast extensor digitorum longus, but not slow soleus, muscles. The underpinning mechanism may include modulation of regenerative myogenesis, as ADAMTS-5 blockade reduced the number of recently repaired desmin positive myofibers without affecting the number of desmin positive muscle progenitor cells. Treatment with the ADAMTS-5 mAb did not significantly affect markers of muscle damage, inflammation, nor fiber size. Altogether, the positive effects of ADAMTS-5 blockade in dystrophic muscles are fiber-type-specific and independent of versican processing.
Language eng
DOI 10.3390/biom10030416
Indigenous content off
Field of Research 0601 Biochemistry and Cell Biology
HERDC Research category C4 Letter or note
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30136758

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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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.