• Login
    View Item 
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Scholarly CommonsCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    About

    AboutCreative CommonsAugusta University LibrariesUSG Copyright Policy

    Statistics

    Display statistics

    Characterization of the sodium coupled vitamin C transporter (SVCT2) and its role in osteoarthritis

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Blackburn_Alan_MS_2011.pdf
    Size:
    2.046Mb
    Format:
    PDF
    Download
    Authors
    Blackburn, Alan Ryan, II
    Issue Date
    2011-06
    URI

    http://hdl.handle.net/10675.2/623601
    
    Metadata
    Show full item record
    Abstract
    Nutrient levels are known to influence the development of osteoarthritis (OA), presumably by modulating levels of matrix biosynthesis and degradation. These processes may be affected by ascorbic acid (AA), which is essential for post-translational modifications of normal collagen. To facilitate AA entry into the chondrocyte, a sodium dependent vitamin C transporter (SVCT2) is primarily expressed. We propose that SVCT2 may play a key role in the normal function of articular chondrocytes, and that a~terations in SVCT2 activity and expression may contribute to cartilage degeneration. This study utilized graded normal and OA human cartilage from 15 patients undergoing a total knee arthroplasty. Portions of this graded tissue were used for RNA isolation and PCR, chondrocyte isolation and in vitro experimentation, and immunofluorescent labeling of SVCT2. Analysis of the expression of SVCT2 mRNA from both healthy and OA explant tissue revealed a significant downregulation (median L\L\Ct of 3.24 cycles, 9.4-fold) of SVCT2 expression in OA tissue (p<O.OOOI). IHC staining clearly demonstrated reduced fluorescence for the SVCT2 transporter in OA tissues. The growth factor BMP-7 and inflammatory factor IL-l significantly increased AA uptake in monolayer cultures by 59% (p<0.0039) and 52% (p<0.0051) respectively. Uptake following oxidative stress (Sin-1) treatments demonstrated an increasing trend with increasing Sin-1 concentration, which was countered by AA addition with Sin-1 treatment at 600uM (p<O.OOOI) and 800uM (p<O.OOOl). Our findings, especially the explant PCR data, support the hypothesis that SVCT2 plays a role in OA, as the expression of the transporter was reduced nearly 10 fold in OA tissue. As AA is an essential nutrient to maintain cartilage integrity, this downregulation in OA implies a significant relationship. Regulatory studies demonstrate increased uptake following treatment with growth factors, inflammatory factors, and oxidative stress. This suggests a role for SVCT2 not only in anabolic processes, but in cellular responses to inflammatory and oxidative conditions as well, indicating that SVCT2 may also play a role in the cellular survival response.
    Affiliation
    Medical College of Georgia
    Collections
    Theses and Dissertations

    entitlement

     
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.