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    Differential effects of warfarin on mRNA levels of developmentally regulated vitamin K dependent proteins, osteocalcin, and matrix GLA protein in vitro

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    Authors
    Barone, Leesa M.
    Aronow, Michael A.
    Tassinari, Melissa S.
    Conlon, Donna
    Canalis, Ernesto
    Stein, Gary S.
    Lian, Jane B.
    UMass Chan Affiliations
    Department of Surgery
    Department of Cell Biology
    Document Type
    Journal Article
    Publication Date
    1994-08-01
    Keywords
    Animals
    Calcium-Binding Proteins
    Cartilage
    Cell Differentiation
    Cell Division
    Cells, Cultured
    *Extracellular Matrix Proteins
    Osteoblasts
    Osteocalcin
    RNA, Messenger
    Rats
    Tumor Cells, Cultured
    Vitamin K
    Warfarin
    Cell Biology
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    Link to Full Text
    http://dx.doi.org/10.1002/jcp.1041600207
    Abstract
    The role of the vitamin K dependent proteins, osteocalcin which is bone specific and matrix Gla protein (MGP) found in many tissues, has been studied by inhibition of synthesis of their characteristic amino acid, gamma-carboxyglutamic acid (Gla) with the anticoagulant sodium warfarin. The effect of sodium warfarin on expression of these proteins, and other phenotypic markers of bone and cartilage during cellular differentiation and development of tissue extracellular matrix, was examined in several model systems. Parameters assayed include cell growth (reflected by histone gene expression) and collagen types I and II, osteopontin, alkaline phosphatase, and mineralization. Studies were carried out in calvarial bone organ cultures, normal diploid rat osteoblast and chondrocyte cultures, and rat osteosarcoma cell lines ROS 17/2.8 and 25/1. In normal diploid cells, warfarin consistently stimulated cell proliferation (twofold). In osteoblast cultures, MGP mRNA levels were generally increased (three to tenfold). Notably, MGP mRNA levels were not affected in chondrocyte cultures, either with chronic or acute warfarin treatments. Osteocalcin mRNA levels and synthesis were decreased up to 50% in ROS 17/2.8 cells and in chronically treated (1 and 5 micrograms/ml sodium warfarin) rat osteoblast cultures after 22 days. Early stages of osteoblast phenotype development from the proliferation period to initial tissue formation (nodules) appeared unaffected; while after day 14, further growth and mineralization of the nodule areas were significantly decreased in warfarin-treated cultures. In summary, warfarin has opposing effects on the expression of two vitamin K dependent proteins, MGP and osteocalcin, in osteoblast cultures and MGP is regulated differently between cartilage and bone as reflected by cellular mRNA levels. Additionally, warfarin effects expression of nonvitamin K dependent proteins which may reflect the influence of warfarin on endoplasmic reticulum associated enzymes.
    Source
    J Cell Physiol. 1994 Aug;160(2):255-64. Link to article on publisher's site
    DOI
    10.1002/jcp.1041600207
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/49658
    PubMed ID
    8040186
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1002/jcp.1041600207
    Scopus Count
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