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This study was undertaken to examine the expression and role of TRPV2 in adult articular cartilage and the development of osteoarthritis (OA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined TRPV2 expression in mouse and human articular cartilage. We analyzed the development of OA in <jats:italic>Col2a1\u2010Cre<jats:sup><jats:italic>ERt2<\/jats:italic><\/jats:sup><\/jats:italic>;<jats:italic>Trpv2<jats:sup>fl\/fl<\/jats:sup><\/jats:italic> mice and <jats:italic>Trpv2<jats:sup>fl\/fl<\/jats:sup><\/jats:italic> littermates in the resection of the medial meniscus and medial collateral ligament model (n = 5 each), the destabilization of the medial meniscus model (n = 5 each), and the aging mouse model (n = 8\u20139 each). We examined marker protein expression in these joints, Ca<jats:sup>2+<\/jats:sup> influx by mechanical stimuli, and downstream pathways in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TRPV2 was expressed in mouse and human articular cartilage and ectopic ossification lesions. In all mouse models of OA examined, <jats:italic>Col2a1\u2010Cre<jats:sup><jats:italic>ERt2<\/jats:italic><\/jats:sup><\/jats:italic>;<jats:italic>Trpv2<jats:sup>fl\/fl<\/jats:sup><\/jats:italic> mice were observed to have enhanced degradation of articular cartilage accompanied by decreased expression of lubricin\/<jats:italic>Prg<\/jats:italic><jats:italic>4<\/jats:italic>, and marked formation of periarticular ectopic ossification. Mechanical stress\u2013induced Ca<jats:sup>2+<\/jats:sup> influx was decreased by <jats:italic>Trpv2<\/jats:italic> knockout (KO). <jats:italic>Prg4<\/jats:italic> induction by fluid\u2010flow shear stress was diminished in <jats:italic>Trpv2<\/jats:italic>\u2010KO mouse chondrocytes, and this was mediated by the Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010dependent protein kinase kinase\u2010cyclic AMP response element binding protein axis. Hypertrophic differentiation was enhanced in <jats:italic>Trpv2<\/jats:italic>\u2010KO mouse chondrocytes. Increased activity of calcineurin and nuclear translocation of nuclear factor in activated T cells 1 induced by fluid\u2010flow shear stress or TRP agonist treatment was reversed by <jats:italic>Trpv2<\/jats:italic> knockout.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings demonstrate regulation of articular cartilage by TRPV2 through <jats:italic>Prg4<\/jats:italic> induction and suppression of ectopic ossification.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41684","type":"journal-article","created":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T20:47:36Z","timestamp":1613508456000},"page":"1441-1450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Involvement of Transient Receptor Potential Vanilloid Channel 2 in the Induction of Lubricin and Suppression of Ectopic Endochondral Ossification in Mouse Articular\u00a0Cartilage"],"prefix":"10.1002","volume":"73","author":[{"given":"Hideki","family":"Nakamoto","sequence":"first","affiliation":[{"name":"University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Katanosaka","sequence":"additional","affiliation":[{"name":"Okayama University  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3125-4818","authenticated-orcid":false,"given":"Ryota","family":"Chijimatsu","sequence":"additional","affiliation":[{"name":"University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Mori","sequence":"additional","affiliation":[{"name":"University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjun","family":"Xuan","sequence":"additional","affiliation":[{"name":"University of Tokyo  Tokyo 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