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The animals were treated with placebo or HNE\u2010trapping carnosine (5 or 20 mg\/kg\/day) orally for 8 weeks. Another group of dogs was treated for 4 weeks with 20 mg\/kg\/day of carnosine starting 4 weeks after surgery. Sham\u2010operated dogs served as controls. In the second experimental protocol, a pathophysiologic dose of HNE (80 nmoles\/ml) or vehicle was injected weekly into the right knee joints of crossbred dogs (n = 6 per group) for 8 weeks. Articular cartilage was subjected to macroscopic, histomorphologic, and immunohistochemical analyses. Cartilage\u2010degrading enzymes and oxidative stress\u2013related products were assessed in synovial fluid and cartilage explants. Markers of inflammation were evaluated in synovium and synovial fluid.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In dogs that had undergone ACLT, carnosine treatment reduced the severity and histopathology score of OA cartilage lesions and also decreased HNE\u2013protein adducts, pentosidine, nitrosylated proteins, cartilage\u2010degrading enzymes, and markers of inflammation. Intraarticular injection of HNE induced cartilage lesions, as assessed by macroscopic and microscopic criteria. Cartilage\u2010degrading enzymes and markers of inflammation increased in HNE\u2010treated dogs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first in vivo study to demonstrate the pathophysiologic role of HNE in OA. That carnosine abolishes HNE production and a number of factors known to be involved in OA pathogenesis renders it a clinically valuable agent in prevention of the disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38704","type":"journal-article","created":{"date-parts":[[2014,5,16]],"date-time":"2014-05-16T11:29:40Z","timestamp":1400239780000},"page":"2461-2471","source":"Crossref","is-referenced-by-count":27,"title":["New Evidence Implicating 4\u2010Hydroxynonenal in the Pathogenesis of Osteoarthritis In Vivo"],"prefix":"10.1002","volume":"66","author":[{"given":"Qin","family":"Shi","sequence":"first","affiliation":[{"name":"H\u00f4pital du Sacr\u00e9\u2010Coeur de Montr\u00e9al and Universit\u00e9 de Montr\u00e9al, Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamilah","family":"Abusarah","sequence":"additional","affiliation":[{"name":"H\u00f4pital du Sacr\u00e9\u2010Coeur de Montr\u00e9al and Universit\u00e9 de Montr\u00e9al, 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