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

Jae Hwan Jeong, Youn Kwan Jung, Hyo Jin Kim, Jung Sook Jin, Hyun Nam Kim, Sang Min Kang, Shin Yoon Kim, Andre J van Wijnen, Janet L. Stein, Jane B. Lian, Gary S. Stein, Shigeaki Kato, Je Yong Choi

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)2365-2375
Number of pages11
JournalMolecular and Cellular Biology
Volume30
Issue number10
DOIs
StatePublished - May 2010
Externally publishedYes

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Aromatase
Estrogens
Enzymes
Genes
Osteoblasts
Steroids
Hormones
Bone and Bones
Chromatin Immunoprecipitation
Bone Density
Mammals
Cultured Cells
Homeostasis
Transcription Factors
Binding Sites
Gene Expression

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

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

In: Molecular and Cellular Biology, Vol. 30, No. 10, 05.2010, p. 2365-2375.

Research output: Contribution to journalArticle

Jeong, JH, Jung, YK, Kim, HJ, Jin, JS, Kim, HN, Kang, SM, Kim, SY, van Wijnen, AJ, Stein, JL, Lian, JB, Stein, GS, Kato, S & Choi, JY 2010, 'The gene for aromatase, a rate-limiting enzyme for local estrogen biosynthesis, is a downstream target gene of Runx2 in skeletal tissues', Molecular and Cellular Biology, vol. 30, no. 10, pp. 2365-2375. https://doi.org/10.1128/MCB.00672-09
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. / The gene for aromatase, a rate-limiting enzyme for local estrogen biosynthesis, is a downstream target gene of Runx2 in skeletal tissues. In: Molecular and Cellular Biology. 2010 ; Vol. 30, No. 10. pp. 2365-2375.
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