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In addition, <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>\u201012 is reported to be required for inflammation in otherwise healthy subjects. This study was undertaken to determine the role of <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>\u201012 and the underlying mechanisms in the pathogenesis of inflammatory arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The collagen\u2010induced arthritis (<jats:styled-content style=\"fixed-case\">CIA<\/jats:styled-content>) model was established in <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>\u201012\u2013deficient mice and their control littermates to determine the role of <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>\u201012 in\u00a0vivo. Micro\u2013computed tomography scanning was used to demonstrate the destruction of the ankle joint; histologic analysis illustrated synovitis, pannus formation, and bone and cartilage destruction; enzyme\u2010linked immunosorbent assay was performed to measure serum levels of inflammatory cytokines; and protein\u2013protein interaction assays were performed to detect the interactions of <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>\u201012 and its various deletion mutants with connective tissue growth factor (<jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Deficiency of <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>\u201012 led to accelerated inflammatory arthritis in the <jats:styled-content style=\"fixed-case\">CIA<\/jats:styled-content> mouse model. Loss of <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>\u201012 caused enhanced osteoclastogenesis. In vitro and in\u00a0vivo protein\u2013protein interaction assays demonstrated that ADAMTS\u201012 bound and processed <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content>, a previously unrecognized substrate of <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>\u201012. In addition, deletion of <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>\u201012 enhanced, while overexpression of <jats:styled-content style=\"fixed-case\">ADMATS<\/jats:styled-content>\u201012 reduced, <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content>\u2010mediated inflammation. Furthermore, <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>\u201012 regulation of inflammation was largely lost in <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content>\u2010deficient macrophages. Importantly, blocking of <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content> attenuated elevated inflammatory arthritis seen in the <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>\u201012\u2013deficient <jats:styled-content style=\"fixed-case\">CIA<\/jats:styled-content> mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study provides evidence that ADAMTS\u201012 is a critical regulator of inflammatory arthritis and that this is mediated, at least in part, through control of <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content> turnover.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40552","type":"journal-article","created":{"date-parts":[[2018,5,11]],"date-time":"2018-05-11T05:14:40Z","timestamp":1526015680000},"page":"1745-1756","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Role of <scp>ADAMTS<\/scp>\u201012 in Protecting Against Inflammatory Arthritis in Mice By Interacting With and Inactivating Proinflammatory Connective Tissue Growth Factor"],"prefix":"10.1002","volume":"70","author":[{"given":"Jian\u2010lu","family":"Wei","sequence":"first","affiliation":[{"name":"New York University Medical Center, New York, New York, and Shandong University Qilu Hospital Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyu","family":"Fu","sequence":"additional","affiliation":[{"name":"New York University Medical Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubryanna","family":"Hettinghouse","sequence":"additional","affiliation":[{"name":"New York University Medical Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010jun","family":"He","sequence":"additional","affiliation":[{"name":"New York University Medical Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth E.","family":"Lipson","sequence":"additional","affiliation":[{"name":"FibroGen, Inc. 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