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Osteoblast-Specific Transcription Factor Osterix Increases Vitamin D Receptor Gene Expression in Osteoblasts
被引:31
作者:

Zhang, Chi
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机构:
Univ Texas SW Med Ctr Dallas, Texas Scottish Rite Hosp Children, Bone Res Lab, Dallas, TX 75390 USA
Univ Texas SW Med Ctr Dallas, Dept Orthoped Surg, Dallas, TX 75390 USA
Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA Univ Texas SW Med Ctr Dallas, Texas Scottish Rite Hosp Children, Bone Res Lab, Dallas, TX 75390 USA

Tang, Wanjin
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Univ Texas SW Med Ctr Dallas, Texas Scottish Rite Hosp Children, Bone Res Lab, Dallas, TX 75390 USA Univ Texas SW Med Ctr Dallas, Texas Scottish Rite Hosp Children, Bone Res Lab, Dallas, TX 75390 USA

Li, Yang
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Univ Texas SW Med Ctr Dallas, Texas Scottish Rite Hosp Children, Bone Res Lab, Dallas, TX 75390 USA Univ Texas SW Med Ctr Dallas, Texas Scottish Rite Hosp Children, Bone Res Lab, Dallas, TX 75390 USA

Yang, Fan
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Univ Texas SW Med Ctr Dallas, Texas Scottish Rite Hosp Children, Bone Res Lab, Dallas, TX 75390 USA Univ Texas SW Med Ctr Dallas, Texas Scottish Rite Hosp Children, Bone Res Lab, Dallas, TX 75390 USA

Dowd, Diane R.
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机构:
Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA Univ Texas SW Med Ctr Dallas, Texas Scottish Rite Hosp Children, Bone Res Lab, Dallas, TX 75390 USA

MacDonald, Paul N.
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h-index: 0
机构:
Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA Univ Texas SW Med Ctr Dallas, Texas Scottish Rite Hosp Children, Bone Res Lab, Dallas, TX 75390 USA
机构:
[1] Univ Texas SW Med Ctr Dallas, Texas Scottish Rite Hosp Children, Bone Res Lab, Dallas, TX 75390 USA
[2] Univ Texas SW Med Ctr Dallas, Dept Orthoped Surg, Dallas, TX 75390 USA
[3] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA
[4] Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA
来源:
关键词:
BONE-FORMATION;
MEDIATED TRANSCRIPTION;
DIFFERENTIATION;
RICKETS;
PROTEIN;
CELLS;
MICE;
1,25-DIHYDROXYVITAMIN-D;
HOMEOSTASIS;
ALOPECIA;
D O I:
10.1371/journal.pone.0026504
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Osterix (Osx) is an osteoblast-specific transcription factor required for osteoblast differentiation from mesenchymal stem cells. In Osx knock-out mice, no bone formation occurs. The vitamin D receptor (VDR) is a member of the nuclear hormone receptor superfamily that regulates target gene transcription to ensure appropriate control of calcium homeostasis and bone development. Here, we provide several lines of evidence that show that the VDR gene is a target for transcriptional regulation by Osx in osteoblasts. For example, calvaria obtained from Osx-null embryos displayed dramatic reductions in VDR expression compared to wild-type calvaria. Stable overexpression of Osx stimulated VDR expression in C2C12 mesenchymal cells. Inhibition of Osx expression by siRNA led to downregulation of VDR. In contrast, Osx levels remained unchanged in osteoblasts in VDR-null mice. Mechanistic approaches using transient transfection assays showed that Osx directly activated a 1 kb fragment of the VDR promoter in a dose-dependent manner. To define the region of the VDR promoter that was responsive to Osx, a series of VDR promoter deletion mutants were examined and the minimal Osx-responsive region was refined to the proximal 120 bp of the VDR promoter. Additional point mutants were used to identify two GC-rich regions that were responsible for VDR promoter activation by Osx. Chromatin immunoprecipitation assays demonstrated that endogenous Osx was associated with the native VDR promoter in primary osteoblasts in vivo. Cumulatively, these data strongly support a direct regulatory role for Osx in VDR gene expression. They further provide new insight into potential mechanisms and pathways that Osx controls in osteoblasts and during the process of osteoblastic cell differentiation.
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机构: OSAKA UNIV,SCH MED,DEPT PATHOL,SUITA,OSAKA 565,JAPAN

Yoshiki, S
论文数: 0 引用数: 0
h-index: 0
机构: OSAKA UNIV,SCH MED,DEPT PATHOL,SUITA,OSAKA 565,JAPAN

Kishimoto, T
论文数: 0 引用数: 0
h-index: 0
机构: OSAKA UNIV,SCH MED,DEPT PATHOL,SUITA,OSAKA 565,JAPAN
[10]
Targeted ablation of the vitamin D receptor: An animal model of vitamin D-dependent rickets type II with alopecia
[J].
Li, YC
;
Pirro, AE
;
Amling, M
;
Delling, G
;
Baroni, R
;
Bronson, R
;
DeMay, MB
.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
1997, 94 (18)
:9831-9835

Li, YC
论文数: 0 引用数: 0
h-index: 0
机构: MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114

Pirro, AE
论文数: 0 引用数: 0
h-index: 0
机构: MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114

Amling, M
论文数: 0 引用数: 0
h-index: 0
机构: MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114

Delling, G
论文数: 0 引用数: 0
h-index: 0
机构: MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114

Baroni, R
论文数: 0 引用数: 0
h-index: 0
机构: MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114

Bronson, R
论文数: 0 引用数: 0
h-index: 0
机构: MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114

DeMay, MB
论文数: 0 引用数: 0
h-index: 0
机构: MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114