{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T08:29:52Z","timestamp":1771489792170,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,7]],"date-time":"2020-03-07T00:00:00Z","timestamp":1583539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Financial Markets Foundation for Children Grant","award":["162-2010"],"award-info":[{"award-number":["162-2010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/biom10030416","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T05:37:34Z","timestamp":1583732254000},"page":"416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Treatment of Dystrophic mdx Mice with an ADAMTS-5 Specific Monoclonal Antibody Increases the Ex Vivo Strength of Isolated Fast Twitch Hindlimb Muscles"],"prefix":"10.3390","volume":"10","author":[{"given":"Alex","family":"Addinsall","sequence":"first","affiliation":[{"name":"Centre for Molecular and Medical Research, School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia"},{"name":"Department of Physiology and Pharmacology, Karolinska Insitutet, 171 77 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard","family":"Forgan","sequence":"additional","affiliation":[{"name":"Centre for Molecular and Medical Research, School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha","family":"McRae","sequence":"additional","affiliation":[{"name":"Centre for Molecular and Medical Research, School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhys","family":"Kelly","sequence":"additional","affiliation":[{"name":"Centre for Molecular and Medical Research, School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penny","family":"McDonald","sequence":"additional","affiliation":[{"name":"Centre for Molecular and Medical Research, School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryony","family":"McNeil","sequence":"additional","affiliation":[{"name":"Centre for Molecular and Medical Research, School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"McCulloch","sequence":"additional","affiliation":[{"name":"Centre for Molecular and Medical Research, School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Stupka","sequence":"additional","affiliation":[{"name":"Centre for Molecular and Medical Research, School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia"},{"name":"Department of Medicine\u2014Western Health, The University of Melbourne, St. Albans, VIC 3021, Australia"},{"name":"Australian Institute for Musculoskeletal Science (AIMSS), 176 Furlong Road, St. Albans, VIC 3021, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/S0140-6736(12)61897-2","article-title":"Muscular dystrophies","volume":"381","author":"Mercuri","year":"2013","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1136\/thx.53.11.949","article-title":"Impact of nasal ventilation on survival in hypercapnic Duchenne muscular dystrophy","volume":"53","author":"Simonds","year":"1998","journal-title":"Thorax"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.bbadis.2006.06.009","article-title":"Current treatment of adult Duchenne muscular dystrophy","volume":"1772","author":"Wagner","year":"2007","journal-title":"Biochimica et Biophysica Acta (BBA) - Mol. 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