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The joints were sectioned and analyzed histochemically for damage to cartilage and expression of DR3, TL1A, Ly\u20106G (a marker for neutrophils), the gelatinase matrix metalloproteinase 9 (MMP\u20109), the aggrecanase ADAMTS\u20105, and the neutrophil chemoattractant CXCL1. In vitro production of MMP\u20109 was measured in cultures from fibroblasts, macrophages, and neutrophils following the addition of TL1A and other proinflammatory stimuli.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>DR3 expression was up\u2010regulated in the joints of wild\u2010type mice following generation of AIA. DR3<jats:sup>\u2212\/\u2212<\/jats:sup> mice were protected against cartilage damage compared with wild\u2010type mice, even at early time points prior to the main accumulation of Teff cells in the joint. Early protection against AIA in vivo correlated with reduced levels of MMP\u20109. In vitro, neutrophils were major producers of MMP\u20109, while neutrophil numbers were reduced in the joints of DR3<jats:sup>\u2212\/\u2212<\/jats:sup> mice. However, TL1A neither induced MMP\u20109 release nor affected the survival of neutrophils. Instead, reduced levels of CXCL1 were observed in the joints of DR3<jats:sup>\u2212\/\u2212<\/jats:sup> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>DR\u20103 drives early cartilage destruction in the AIA model of inflammatory arthritis through the release of CXCL1, maximizing neutrophil recruitment to the joint and leading to enhanced local production of cartilage\u2010destroying enzymes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38770","type":"journal-article","created":{"date-parts":[[2014,7,7]],"date-time":"2014-07-07T14:09:15Z","timestamp":1404742155000},"page":"2762-2772","source":"Crossref","is-referenced-by-count":28,"title":["Regulation of Early Cartilage Destruction in Inflammatory Arthritis by Death Receptor 3"],"prefix":"10.1002","volume":"66","author":[{"given":"Eddie C. 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