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  • Increased formation and decreased resorption of bone in mice with elevated vitamin D receptor in mature cells of the osteoblastic lineage.

    Author(s)
    Gardiner, EM
    Baldock, PA
    Thomas, GP
    Sims, NA
    Henderson, NK
    Hollis, B
    White, CP
    Sunn, KL
    Morrison, NA
    Walsh, WR
    Eisman, JA
    Griffith University Author(s)
    Morrison, Nigel A.
    Year published
    2000
    Metadata
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    Abstract
    The microarchitecture of bone is regulated by complex interactions between the bone-forming and resorbing cells, and several compounds regulate both actions. For example, vitamin D, which is required for bone mineralization, also stimulates bone resorption. Transgenic mice overexpressing the vitamin D receptor solely in mature cells of the osteoblastic bone-forming lineage were generated to test the potential therapeutic value of shifting the balance of vitamin D activity in favor of bone formation. Cortical bone was 5% wider and 15% stronger in these mice due to a doubling of periosteal mineral apposition rate without altered ...
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    The microarchitecture of bone is regulated by complex interactions between the bone-forming and resorbing cells, and several compounds regulate both actions. For example, vitamin D, which is required for bone mineralization, also stimulates bone resorption. Transgenic mice overexpressing the vitamin D receptor solely in mature cells of the osteoblastic bone-forming lineage were generated to test the potential therapeutic value of shifting the balance of vitamin D activity in favor of bone formation. Cortical bone was 5% wider and 15% stronger in these mice due to a doubling of periosteal mineral apposition rate without altered body weight or calcium homeostatic hormone levels. A 20% increase in trabecular bone volume in transgenic vertebrae was also observed, unexpectedly associated with a 30% reduction in resorption surface rather than greater bone formation. These findings indicate anabolic vitamin D activity in bone and identify a previously unknown pathway from mature osteoblastic cells to inhibit osteoclastic bone resorption, counterbalancing the known stimulatory action through immature osteoblastic cells. A therapeutic approach that both stimulates cortical anabolic and inhibits trabecular resorptive pathways would be ideal for treatment of osteoporosis and other osteopenic disorders.
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    Journal Title
    Federation of American Societies for Experimental Biology (FASEB J)
    Volume
    14
    Issue
    13
    DOI
    https://doi.org/10.1096/fj.99-1075com
    Subject
    Biochemistry and Cell Biology
    Physiology
    Medical Physiology
    Publication URI
    http://hdl.handle.net/10072/67385
    Collection
    • Journal articles

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