Vitamin K Induces Osteoblast Differentiation through Pregnane X Receptor-Mediated Transcriptional Control of the Msx2 Gene
-
Published:2007-11-15
Issue:22
Volume:27
Page:7947-7954
-
ISSN:0270-7306
-
Container-title:Molecular and Cellular Biology
-
language:en
-
Short-container-title:Mol Cell Biol
Author:
Igarashi Mamoru1, Yogiashi Yoshiko12, Mihara Masatomo1, Takada Ichiro1, Kitagawa Hirochika1, Kato Shigeaki12
Affiliation:
1. The Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan 2. ERATO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
Abstract
ABSTRACT
Vitamin K is a fat-soluble vitamin that serves as a coenzyme for vitamin K-dependent carboxylase. Besides its canonical action, vitamin K binds to the steroid and xenobiotic receptor (SXR)/pregnane X receptor (PXR) and modulates gene transcription. To determine if the osteoprotective action of vitamin K is the result of the PXR/SXR pathway, we screened by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis the PXR/SXR target genes in an osteoblastic cell line (MC3T3-E1) treated with a vitamin K2 (menaquinone 4 [MK4]). Osteoblastic differentiation of MC3T3-E1 cells was induced by MK4. Msx2, an osteoblastogenic transcription factor, was identified as an MK4-induced gene. Functional analysis of the Msx2 gene promoter mapped a vitamin K-responsive element (PXR-responsive element [PXRE]) that was directly bound by a PXR/retinoid X receptor α heterodimer. In a chromatin immunoprecipitation analysis, PXR was recruited together with a coactivator, p300, to the PXRE in the Msx2 promoter. MK4-bound PXR cooperated with estrogen-bound estrogen receptor α to control transcription at the Msx2 promoter. Knockdown of either PXR or Msx2 attenuated the effect of MK4 on osteoblastic differentiation. Thus, the present study suggests that Msx2 is a target gene for PXR activated by vitamin K and suggests that the osteoprotective action of MK4 in the human mediates, at least in part, a genomic pathway of vitamin K signaling.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Reference38 articles.
1. Bertilsson, G., J. Heidrich, K. Svensson, M. Åsman, L. Jendeberg, M. Syndow-Bäckman, R. Ohlsson, H. Postlind, P. Blomquist, and A. Berkenstam. 1998. Identification of a human nuclear receptor defines a new signaling pathway for CYP3A4 induction. Proc. Natl. Acad. Sci. USA95:12208-12213. 2. Blumberg, B., W. Sabbagh, Jr., H. Juguilon, J. Bolado, Jr., C. M. van Meter, E. S. Ong, and R. M. Evans. 1998. SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Gene Dev.12:3195-3205. 3. Booth, S. L., K. L. Tucker, H. Chen, M. T. Hannan, D. R. Gagnon, L. A. Cupples, P. W. F. Wilson, J. Ordovas, E. J. Schaefer, B. Dawson-Hughes, and D. P. Kiel. 2000. Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am. J. Clin. Nutr.71:1201-1208. 4. Ducy, P., C. Desbois, B. Boyce, G. Pinero, B. Story, C. Dunstan, E. Smith, J. Bonadio, S. Goldstein, C. Gundberg, A. Bradley, and G. Karsenty. 1996. Increased bone formation in osteocalcin-deficient mice. Nature382:448-452. 5. Fujiki, R., M. S. Kim, Y. Sasaki, K. Yoshimura, H. Kitagawa, and S. Kato. 2005. Ligand-induced transrepression by VDR through association of WSTF with acetylated histones. EMBO J.24:3881-3894.
Cited by
73 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|