Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2010-4-27
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1098-5549
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2365-75
pubmed:dateRevised
2011-2-11
pubmed:meshHeading
pubmed-meshheading:20231365-Animals, pubmed-meshheading:20231365-Aromatase, pubmed-meshheading:20231365-Base Sequence, pubmed-meshheading:20231365-Bone Density, pubmed-meshheading:20231365-Bone and Bones, pubmed-meshheading:20231365-Cell Line, pubmed-meshheading:20231365-Core Binding Factor Alpha 1 Subunit, pubmed-meshheading:20231365-Embryo, Mammalian, pubmed-meshheading:20231365-Estrogens, pubmed-meshheading:20231365-Exons, pubmed-meshheading:20231365-Female, pubmed-meshheading:20231365-Gene Expression Regulation, Enzymologic, pubmed-meshheading:20231365-Humans, pubmed-meshheading:20231365-Mice, pubmed-meshheading:20231365-Mice, Knockout, pubmed-meshheading:20231365-Molecular Sequence Data, pubmed-meshheading:20231365-Osteoblasts, pubmed-meshheading:20231365-Progesterone, pubmed-meshheading:20231365-Promoter Regions, Genetic
pubmed:year
2010
pubmed:articleTitle
The gene for aromatase, a rate-limiting enzyme for local estrogen biosynthesis, is a downstream target gene of Runx2 in skeletal tissues.
pubmed:affiliation
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, 101 Dongin-Dong, Jung-Gu, Daegu 700-422, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't