{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:06:22Z","timestamp":1760234782485,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Heart and Stroke Foundation of Ontario","award":["G-19-0026307"],"award-info":[{"award-number":["G-19-0026307"]}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2017-06336"],"award-info":[{"award-number":["RGPIN-2017-06336"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>A full understanding of the molecular mechanisms implicated in the etiopathogenesis of juvenile idiopathic arthritis (JIA) is lacking. A critical role for leukocyte proteolytic activity (e.g., elastase and cathepsin G) has been proposed. While leukocyte elastase\u2019s (HLE) role has been documented, the potential contribution of proteinase 3 (PR3), a serine protease present in abundance in neutrophils, has not been evaluated. In this study we investigated: (1) PR3 concentrations in the synovial fluid of JIA patients using ELISA and (2) the cartilage degradation potential of PR3 by measuring the hydrolysis of fluorescently labeled collagen II in vitro. In parallel, concentrations and collagen II hydrolysis by HLE were assessed. Additionally, the levels of the co-secreted primary granule protein myeloperoxidase (MPO) were assessed in synovial fluid of patients diagnosed with JIA. We report the following levels of analytes in JIA synovial fluid: PR3\u2014114 \u00b1 100 ng\/mL (mean \u00b1 SD), HLE\u20141272 \u00b1 1219 ng\/mL, and MPO\u20141129 \u00b1 1659 ng\/mL, with a very strong correlation between the PR3 and HLE concentrations (rs = 0.898, p &lt; 1 \u00d7 10\u20136). Importantly, PR3 hydrolyzed fluorescently labeled collagen II as efficiently as HLE. Taken together, these novel findings suggest that PR3 (in addition to HLE) contributes to JIA-associated joint damage.<\/jats:p>","DOI":"10.3390\/pathophysiology28030021","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T21:14:51Z","timestamp":1624482891000},"page":"320-327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Proteinase 3 Contribution to Juvenile Idiopathic Arthritis-Associated Cartilage Damage"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3697-3042","authenticated-orcid":false,"given":"Eric K.","family":"Patterson","sequence":"first","affiliation":[{"name":"Centre for Critical Illness Research, Lawson Health Research Institute, London, ON N6A 5W9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Vanin Moreno","sequence":"additional","affiliation":[{"name":"Centre for Critical Illness Research, Lawson Health Research Institute, London, ON N6A 5W9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5635-3791","authenticated-orcid":false,"given":"Douglas D.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Lawson Health Research Institute, Children\u2019s Health Research Institute, London, ON N6A 5W9, Canada"},{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada"},{"name":"Department of Paediatrics, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gediminas","family":"Cepinskas","sequence":"additional","affiliation":[{"name":"Centre for Critical Illness Research, Lawson Health Research Institute, London, ON N6A 5W9, Canada"},{"name":"Department of Medical Biophysics, Western University, London, ON N6A 5C1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaya","family":"Iida","sequence":"additional","affiliation":[{"name":"Centre for Critical Illness Research, Lawson Health Research Institute, London, ON N6A 5W9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2780-0617","authenticated-orcid":false,"given":"Roberta A.","family":"Berard","sequence":"additional","affiliation":[{"name":"Lawson Health Research Institute, Children\u2019s Health Research Institute, London, ON N6A 5W9, Canada"},{"name":"Department of Paediatrics, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada"},{"name":"Division of Rheumatology, London Health Sciences Centre, Children\u2019s Hospital, London, ON N6A 5W9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,23]]},"reference":[{"key":"ref_1","first-page":"390","article-title":"International League of Associations for Rheumatology Classification of Juvenile Idiopathic Arthritis: Second Revision, Edmonton, 2001","volume":"31","author":"Petty","year":"2004","journal-title":"J. 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