The osteogenic transcription factor runx2 controls genes involved in sterol/steroid metabolism, including CYP11A1 in osteoblasts
Authors
Teplyuk, Nadiya M.Zhang, Ying
Lou, Yang
Hawse, John R.
Hassan, Mohammad Q.
Teplyuk, Viktor
Pratap, Jitesh
Galindo, Mario
Stein, Janet L.
Stein, Gary S.
Lian, Jane B.
Van Wijnen, Andre J.
Document Type
Journal ArticlePublication Date
2009-04-04Keywords
AnimalsCell Differentiation
Cell Proliferation
Cholesterol Side-Chain Cleavage Enzyme
Core Binding Factor Alpha 1 Subunit
*Gene Expression Regulation, Enzymologic
Gene Knockdown Techniques
Humans
Isoenzymes
Mice
Mitochondria
Molecular Weight
Osteoblasts
Osteogenesis
Promoter Regions, Genetic
Protein Transport
RNA, Messenger
RNA, Small Interfering
Reproducibility of Results
Sterols
Transcriptional Activation
Cell Biology
Metadata
Show full item recordAbstract
Steroid hormones including (1,25)-dihydroxyvitamin D3, estrogens, and glucocorticoids control bone development and homeostasis. We show here that the osteogenic transcription factor Runx2 controls genes involved in sterol/steroid metabolism, including Cyp11a1, Cyp39a1, Cyp51, Lss, and Dhcr7 in murine osteoprogenitor cells. Cyp11a1 (P450scc) encodes an approximately 55-kDa mitochondrial enzyme that catalyzes side-chain cleavage of cholesterol and is rate limiting for steroid hormone biosynthesis. Runx2 is coexpressed with Cyp11a1 in osteoblasts as well as nonosseous cell types (e.g. testis and breast cancer cells), suggesting a broad biological role for Runx2 in sterol/steroid metabolism. Notably, osteoblasts and breast cancer cells express an approximately 32-kDa truncated isoform of Cyp11a1 that is nonmitochondrial and localized in both the cytoplasm and the nucleus. Chromatin immunoprecipitation analyses and gel shift assays show that Runx2 binds to the Cyp11a1 gene promoter in osteoblasts, indicating that Cyp11a1 is a direct target of Runx2. Specific Cyp11a1 knockdown with short hairpin RNA increases cell proliferation, indicating that Cyp11a1 normally suppresses osteoblast proliferation. We conclude that Runx2 regulates enzymes involved in sterol/steroid-related metabolic pathways and that activation of Cyp11a1 by Runx2 may contribute to attenuation of osteoblast growth.Source
Molecular Endocrinology. 2009 Jun;23(6):849-61. Epub 2009 Apr 2. Link to article on publisher's siteDOI
10.1210/me.2008-0270Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49607PubMed ID
19342447Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1210/me.2008-0270