• Login
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    ELR+ CXC chemokine signalling in cartilage homeostasis. 
    •   QMRO Home
    • Queen Mary University of London Theses
    • Theses
    • ELR+ CXC chemokine signalling in cartilage homeostasis.
    •   QMRO Home
    • Queen Mary University of London Theses
    • Theses
    • ELR+ CXC chemokine signalling in cartilage homeostasis.
    ‌
    ‌

    Browse

    All of QMROCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    ‌
    ‌

    Administrators only

    Login
    ‌
    ‌

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    ELR+ CXC chemokine signalling in cartilage homeostasis.

    View/Open
    SHERWOODELR+ CXC2011.pdf (3.738Mb)
    Publisher
    Queen Mary University of London
    Metadata
    Show full item record
    Abstract
    The production of ELR+ CXC chemokines is widely studied in arthritis and has been postulated to contribute to the inflammatory phenomena that eventually lead to cartilage breakdown. Healthy articular chondrocytes also express CXC chemokines and chemokine receptors, however their purpose within cartilage is unclear because chondrocytes are encased within a dense avascular extracellular matrix and are not known to migrate in vivo. This study reveals a novel homeostatic function of signalling via CXCR1 and CXCR2 in articular cartilage. Confocal microscopy confirmed the localisation of CXCR1/2 in both in vitro cultured chondrocytes and in human articular cartilage explants at the cell membrane as well as within the cytoplasm, as expected considering the internalisation and recycling of these receptors. Calcium mobilisation assays proved that chondrocyte CXCR1/2 are functional and show a higher redundancy than that found in human neutrophils. Disruption of CXCR1/2 signalling at receptor level or by downstream G-protein inhibition resulted in a reduced extracellular matrix sulphated glycosaminoglycan content, and reduced expression of the cartilage differentiation markers COL2A1, Aggrecan, and SOX9, showing that CXCR1/2 signalling is required for the phenotypic stability of adult articular chondrocytes. In normal cartilage, CXCL6 and CXCL8 are present within the cartilage matrix. CXCL8 is bound to heparan sulphate proteoglycans, whilst CXCL6 is sequestered by an as of yet unidentified alternative matrix interaction, contributing to the determination of the chemokine signalling domain. In vivo analysis of CXCR2 knockout mouse knee joints revealed that mice lacking CXCR2 have significantly thinner epiphyseal growth plates and medial tibial plateaus, suggesting that CXCR signalling may be required in cartilage during periods of high chondrocyte turnover. Pharmacological modulation of the CXCR1/2 signalling pathway may allow for the selective inhibition of catabolic inflammatory responses whilst preserving CXCR1/2 maintained chondrocyte phenotypic homeostasis in articular cartilage.
    Authors
    Sherwood, Joanna
    URI
    http://qmro.qmul.ac.uk/xmlui/handle/123456789/2447
    Collections
    • Theses [3321]
    Copyright statements
    The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author
    Twitter iconFollow QMUL on Twitter
    Twitter iconFollow QM Research
    Online on twitter
    Facebook iconLike us on Facebook
    • Site Map
    • Privacy and cookies
    • Disclaimer
    • Accessibility
    • Contacts
    • Intranet
    • Current students

    Modern Slavery Statement

    Queen Mary University of London
    Mile End Road
    London E1 4NS
    Tel: +44 (0)20 7882 5555

    © Queen Mary University of London.