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  • Title: The loss of α2β1 integrin suppresses joint inflammation and cartilage destruction in mouse models of rheumatoid arthritis.
    Author: Peters MA, Wendholt D, Strietholt S, Frank S, Pundt N, Korb-Pap A, Joosten LA, van den Berg WB, Kollias G, Eckes B, Pap T.
    Journal: Arthritis Rheum; 2012 May; 64(5):1359-68. PubMed ID: 22083543.
    Abstract:
    OBJECTIVE: Integrin α2β1 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 α2β1 integrin in regulating both cell attachment and expression of matrix-degrading enzymes such as matrix metalloproteinases (MMPs), mice that lack the α2 integrin subunit (Itga2(-/-) mice) develop normally and are fertile. We undertook this study to investigate the effect of Itga2 deficiency in 2 different mouse models of destructive arthritis: the antigen-induced arthritis (AIA) mouse model and the human tumor necrosis factor α (TNFα)-transgenic mouse model. METHODS: AIA was induced in the knee joints of Itga2(-/-) mice and wild-type controls. Human TNF-transgenic mice were crossed with Itga2(-/-) 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. RESULTS: Under arthritic conditions, Itga2 deficiency led to decreased severity of joint pathology. Specifically, Itga2(-/-) mice showed less severe clinical symptoms and dramatically reduced pannus formation and cartilage erosion. Mice lacking α2β1 integrin exhibited reduced MMP-3 expression, both in their sera and in fibroblast-like synoviocytes (FLS), due to impaired ERK activation. Further, both the proliferation and attachment of FLS to cartilage were partially dependent on α2β1 integrin in vitro and in vivo. CONCLUSION: Our findings suggest that α2β1 integrin contributes significantly to inflammatory cartilage destruction by promoting fibroblast proliferation and attachment and MMP expression.
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