• 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

    The Role of Stromal Cell-Derived Factor-1Β in Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem/Stromal Cells and Bone Formation

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Herberg, Samuel A.
    Issue Date
    2013-03
    URI
    http://hdl.handle.net/10675.2/317023
    
    Metadata
    Show full item record
    Abstract
    The experiments performed for this dissertation tested the hypotheses that SDF-1β enhances osteogenic differentiation of BMSCs, promotes engraftment and bone formation following whole-body irradiation, and potentiates suboptimal BMP-2 osteoinduction in a model of acute bone injury. We used multipotent primary BMSCs from 18-month-old C57BL/6J mice, genetically modified to overexpress SDF-1β, to ask whether SDF-1β played a role in cell survival and osteogenic differentiation of BMSCs in vitro. Our studies revealed that SDF-1β protected BMSCs from oxidative stress through increasing autophagy and decreasing apoptosis, independent from potential effects on cell proliferation. In support of the hypothesis we also found that SDF-1β enhanced calcium mineral deposition (independent of BMP-2 co-stimulation), upregulated key osteogenic markers, and increased phosphorylation of intracellular Erk1/2 and Smad1/5/8, thereby potentiating BMP-2 signal transduction during osteogenic differentiation, which was attenuated by blocking CXCR4 signaling. We next inquired whether SDF-1β promotes BMSC engraftment and new bone formation. Using direct tibial transplantation in irradiation-preconditioned animals, we found that SDF-1β enhanced new trabecular bone formation upon local BMSC transplantation. The data furthermore suggested that the differential proteolytic clearance of SDF-1 splice variants in the systemic and local environment following myeloablative injury may be an important determinant in the success of stem cell therapy protocols. The suggestion that SDF-1β could regulate BMP-2 osteoinduction through regulating CXCR4 signaling was compelling because several studies have reported a comparable effect using SDF-1α. We examined the direct contribution of SDF-1β to BMP-2 osteoinduction in a critical-size calvaria osteotomy model and found a dose-dependent ability of SDF-1β to potentiate suboptimal BMP-2-induced bone formation to levels comparable to those obtained with the 10-fold higher optimal/benchmark BMP-2 dose, which was blunted by perturbing CXCR4 signaling. These in vitro and in vivo findings expand our understanding of BMP-2 osteoinduction and implicate osteogenesis-enhancing properties of SDF-1β pointing towards its translational potential for cell therapy and regenerative medicine applications. It appears feasible for SDF-1β to improve bone regeneration in a variety of orthopaedic situations and ultimately reduce the burden of musculoskeletal injuries.
    Affiliation
    Department of Cellular Biology and Anatomy
    Collections
    Theses and Dissertations
    Department of Cellular Biology and Anatomy 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.