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We undertook this study to investigate the role of L\u2010PGDS<\/jats:styled-content> in the pathogenesis of osteoarthritis (OA<\/jats:styled-content>) using an experimental mouse model.<\/jats:p><\/jats:sec>Methods<\/jats:title>Experimental OA<\/jats:styled-content> was induced in wild\u2010type (WT<\/jats:styled-content>) and L\u2010PGDS<\/jats:styled-content>\u2013deficient (L\u2010PGDS<\/jats:styled-content>\u2212\/\u2212<\/jats:sup>) mice (n = 10 per genotype) by destabilization of the medial meniscus (DMM<\/jats:styled-content>). Cartilage degradation was evaluated by histology. The expression of matrix metalloproteinase 13 (MMP<\/jats:styled-content>\u201013) and ADAMTS<\/jats:styled-content>\u20105 was assessed by immunohistochemistry. Bone changes were determined by micro\u2013computed tomography. Cartilage explants from L\u2010PGDS<\/jats:styled-content>\u2212\/\u2212<\/jats:sup> and WT<\/jats:styled-content> mice (n = 6 per genotype) were treated with interleukin\u20101\u03b1 (IL<\/jats:styled-content>\u20101\u03b1) ex vivo in order to evaluate proteoglycan degradation. Moreover, the effect of intraarticular injection of a recombinant adeno\u2010associated virus type 2\/5 (rAAV<\/jats:styled-content>2\/5) encoding L\u2010PGDS<\/jats:styled-content> on OA<\/jats:styled-content> progression was evaluated in WT<\/jats:styled-content> mice (n = 9 per group).<\/jats:p><\/jats:sec>Results<\/jats:title>Compared to WT<\/jats:styled-content> mice, L\u2010PGDS<\/jats:styled-content>\u2212\/\u2212<\/jats:sup> mice had exacerbated cartilage degradation and enhanced expression of MMP<\/jats:styled-content>\u201013 and ADAMTS<\/jats:styled-content>\u20105 (P<\/jats:italic>\u00a0< 0.05). Furthermore, L\u2010PGDS<\/jats:styled-content>\u2212\/\u2212<\/jats:sup> mice displayed increased synovitis and subchondral bone changes (P<\/jats:italic>\u00a0< 0.05). Cartilage explants from L\u2010PGDS<\/jats:styled-content>\u2212\/\u2212<\/jats:sup> mice showed enhanced proteoglycan degradation following treatment with IL<\/jats:styled-content>\u20101\u03b1 (P<\/jats:italic>\u00a0< 0.05). Intraarticular injection of rAAV<\/jats:styled-content>2\/5 encoding L\u2010PGDS<\/jats:styled-content> attenuated the severity of DMM<\/jats:styled-content>\u2010induced OA<\/jats:styled-content>\u2010like changes in WT<\/jats:styled-content> mice (P<\/jats:italic>\u00a0< 0.05). The L\u2010PGDS<\/jats:styled-content> level was increased\u00a0in OA<\/jats:styled-content> tissues of WT<\/jats:styled-content> mice (P<\/jats:italic>\u00a0< 0.05).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Collectively, these findings suggest a protective role of L\u2010PGDS<\/jats:styled-content> in OA<\/jats:styled-content>, and therefore enhancing levels of L\u2010PGDS<\/jats:styled-content> may constitute a promising therapeutic strategy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41297","type":"journal-article","created":{"date-parts":[[2020,4,26]],"date-time":"2020-04-26T12:37:10Z","timestamp":1587904630000},"page":"1524-1533","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Role of Lipocalin\u2010Type Prostaglandin D Synthase in Experimental Osteoarthritis"],"prefix":"10.1002","volume":"72","author":[{"given":"Mehdi","family":"Najar","sequence":"first","affiliation":[{"name":"University of Montreal 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