• Login
    View Item 
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsProfilesView

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Regulation of osteoblast development by Bcl-2-associated athanogene-1 (BAG-1).

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    161028srep33504.pdf
    Size:
    1.924Mb
    Format:
    PDF
    Description:
    Full text, Open Access Article
    Download
    Authors
    Greenhough, Joanna
    Papadakis, Emmanouil S
    Cutress, Ramsey I
    Townsend, Paul A
    Oreffo, Richard O C
    Tare, Rahul S
    Affiliation
    Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton
    Issue Date
    2016-09-16
    
    Metadata
    Show full item record
    Abstract
    BCL-2-associated athanogene-1 (BAG-1) is expressed by osteoblast-lineage cells; early embryonic lethality in Bag-1 null mice, however, has limited the investigation of BAG-1 function in osteoblast development. In the present study, bone morphogenetic protein-2/BMP-2-directed osteogenic differentiation of bone marrow stromal cells (BMSCs) of Bag-1(+/-) (heterozygous) female mice was decreased significantly. Genes crucial for osteogenic differentiation, bone matrix formation and mineralisation were expressed at significantly lower levels in cultures of Bag-1(+/-) BMSCs supplemented with BMP-2, while genes with roles in inhibition of BMP-2-directed osteoblastogenesis were significantly upregulated. 17-β-estradiol (E2) enhanced responsiveness of BMSCs of wild-type and Bag-1(+/-) mice to BMP-2, and promoted robust BMP-2-stimulated osteogenic differentiation of BMSCs. BAG-1 can modulate cellular responses to E2 by regulating the establishment of functional estrogen receptors (ERs), crucially, via its interaction with heat shock proteins (HSC70/HSP70). Inhibition of BAG-1 binding to HSC70 by the small-molecule chemical inhibitor, Thioflavin-S, and a short peptide derived from the C-terminal BAG domain, which mediates binding with the ATPase domain of HSC70, resulted in significant downregulation of E2/ER-facilitated BMP-2-directed osteogenic differentiation of BMSCs. These studies demonstrate for the first time the significance of BAG-1-mediated protein-protein interactions, specifically, BAG-1-regulated activation of ER by HSC70, in modulation of E2-facilitated BMP-2-directed osteoblast development.
    Citation
    Regulation of osteoblast development by Bcl-2-associated athanogene-1 (BAG-1). 2016, 6:33504 Sci Rep
    Journal
    Scientific Reports
    URI
    http://hdl.handle.net/10541/619983
    DOI
    10.1038/srep33504
    PubMed ID
    27633857
    Type
    Article
    Language
    en
    ISSN
    2045-2322
    ae974a485f413a2113503eed53cd6c53
    10.1038/srep33504
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

    entitlement

     
    DSpace software (copyright © 2002 - 2025)  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.