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    The gene for aromatase, a rate-limiting enzyme for local estrogen biosynthesis, is a downstream target gene of Runx2 in skeletal tissues

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    Authors
    Jeong, Jae-Hwan
    Jung, Youn-Kwan
    Kim, Hyo-Jin
    Jin, Jung-Sook
    Kim, Hyun-Nam
    Kang, Sang-Min
    Kim, Shin-Yoon
    Van Wijnen, Andre J.
    Stein, Janet L.
    Lian, Jane B.
    Stein, Gary S.
    Kato, Shigeaki
    Choi, Je-Yong
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    UMass Chan Affiliations
    Department of Cell Biology
    Document Type
    Journal Article
    Publication Date
    2010-05-17
    Keywords
    Animals
    Aromatase
    Base Sequence
    Bone Density
    Bone and Bones
    Cell Line
    Core Binding Factor Alpha 1 Subunit
    Embryo, Mammalian
    Estrogens
    Exons
    Female
    *Gene Expression Regulation, Enzymologic
    Humans
    Mice
    Mice, Knockout
    Molecular Sequence Data
    Osteoblasts
    Progesterone
    Promoter Regions, Genetic
    Cell Biology
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    Abstract
    The essential osteoblast-related transcription factor Runx2 and the female steroid hormone estrogen are known to play pivotal roles in bone homeostasis; however, the functional interaction between Runx2- and estrogen-mediated signaling in skeletal tissues is minimally understood. Here we provide evidence that aromatase (CYP19), a rate-limiting enzyme responsible for estrogen biosynthesis in mammals, is transcriptionally regulated by Runx2. Consistent with the presence of multiple Runx2 binding sites, the binding of Runx2 to the aromatase promoter was demonstrated in vitro and confirmed in vivo by chromatin immunoprecipitation assays. The bone-specific aromatase promoter is activated by Runx2, and endogenous aromatase gene expression is upregulated by Runx2 overexpression, establishing the aromatase gene as a target of Runx2. The biological significance of the Runx2 transcriptional control of the aromatase gene is reflected by the enhanced estrogen biosynthesis in response to Runx2 in cultured cells. Reduced in vivo expression of skeletal aromatase gene and low bone mineral density are evident in Runx2 mutant mice. Collectively, these findings uncover a novel link between Runx2-mediated osteoblastogenic processes and the osteoblast-mediated biosynthesis of estrogen as an osteoprotective steroid hormone.
    Source
    Molecular and Cellular Biology. 2010 May;30(10):2365-75. Epub 2010 Mar 15. Link to article on publisher's site
    DOI
    10.1128/MCB.00672-09
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/49492
    PubMed ID
    20231365
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1128/MCB.00672-09
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    UMass Chan Faculty and Researcher Publications

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