{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:59:46Z","timestamp":1787579986664,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,4,26]],"date-time":"2012-04-26T00:00:00Z","timestamp":1335398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Integrin \u03b12\u03b21 functions as a major receptor for type I collagen on different cell types, including fibroblasts and inflammatory cells. Although in vitro data suggest a role for \u03b12\u03b21 integrin in regulating both cell attachment and expression of matrix\u2010degrading enzymes such as matrix metalloproteinases (MMPs), mice that lack the \u03b12 integrin subunit (<jats:italic>Itga2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice) develop normally and are fertile. We undertook this study to investigate the effect of<jats:italic>Itga2<\/jats:italic>deficiency in 2 different mouse models of destructive arthritis: the antigen\u2010induced arthritis (AIA) mouse model and the human tumor necrosis factor \u03b1 (TNF\u03b1)\u2013transgenic mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>AIA was induced in the knee joints of<jats:italic>Itga2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice and wild\u2010type controls. Human TNF\u2013transgenic mice were crossed with<jats:italic>Itga2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice and were assessed clinically and histopathologically for signs of arthritis, inflammation, bone erosion, and cartilage damage. MMP expression, proliferation, fibroblast attachment, and ERK activation were determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Under arthritic conditions,<jats:italic>Itga2<\/jats:italic>deficiency led to decreased severity of joint pathology. Specifically,<jats:italic>Itga2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice showed less severe clinical symptoms and dramatically reduced pannus formation and cartilage erosion. Mice lacking \u03b12\u03b21 integrin exhibited reduced MMP\u20103 expression, both in their sera and in fibroblast\u2010like synoviocytes (FLS), due to impaired ERK activation. Further, both the proliferation and attachment of FLS to cartilage were partially dependent on \u03b12\u03b21 integrin in vitro and in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that \u03b12\u03b21 integrin contributes significantly to inflammatory cartilage destruction by promoting fibroblast proliferation and attachment and MMP expression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.33487","type":"journal-article","created":{"date-parts":[[2011,11,14]],"date-time":"2011-11-14T16:12:11Z","timestamp":1321287131000},"page":"1359-1368","source":"Crossref","is-referenced-by-count":62,"title":["The loss of \u03b12\u03b21 integrin suppresses joint inflammation and cartilage destruction in mouse models of rheumatoid arthritis"],"prefix":"10.1002","volume":"64","author":[{"given":"Marvin A.","family":"Peters","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doreen","family":"Wendholt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Strietholt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Frank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noreen","family":"Pundt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelheid","family":"Korb\u2010Pap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo A. 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