Functional Cooperation between Vitamin D Receptor and Runx2 in Vitamin D-Induced Vascular Calcification

被引：39

作者：

Han, Min-Su ^{[1
,2
]}

Che, Xiangguo ^{[1
,2
]}

Cho, Gyoung-Ho ^{[1
,2
]}

Park, Hye-Ri ^{[1
,2
]}

Lim, Kyung-Eun ^{[1
,2
]}

Park, Na-Rae ^{[1
,2
]}

Jin, Jung-Sook ^{[1
,2
]}

Jung, Youn-Kwan ^{[1
,2
]}

Jeong, Jae-Hwan ^{[1
,2
]}

Lee, In-Kyu ^{[3
]}

Kato, Shigeaki ^{[4
]}

Choi, Je-Yong ^{[1
,2
]}

机构：

[1] Kyungpook Natl Univ, Dept Biochem & Cell Biol, WCU Program, Daegu, South Korea

[2] Kyungpook Natl Univ, Plus Program BK21, CMRC, Skeletal Dis Genome Res Ctr,Sch Med, Daegu, South Korea

[3] Kyungpook Natl Univ, Dept Internal Med, Div Endocrinol, Sch Med, Daegu, South Korea

[4] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo, Japan

来源：

PLOS ONE | 2013年 / 8卷 / 12期

基金：

新加坡国家研究基金会;

关键词：

SMOOTH-MUSCLE-CELLS; MICE LACKING; OSTEOCLAST DIFFERENTIATION; OSTEOGENIC REGULATION; BONE-FORMATION; GENE; EXPRESSION; CALCIUM; CBFA1; OSTEOPOROSIS;

D O I：

10.1371/journal.pone.0083584

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：

The transdifferentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells has been implicated in the context of vascular calcification. We investigated the roles of vitamin D receptor (Vdr) and runt-related transcription factor 2 (Runx2) in the osteoblastic differentiation of VSMCs in response to vitamin D-3 using in vitro VSMCs cultures and in vivo in Vdr knockout (Vdr(-/-)) and Runx2 carboxy-terminus truncated heterozygous (Runx2(+/Delta C)) mice. Treatment of VSMCs with active vitamin D-3 promoted matrix mineral deposition, and increased the expressions of Vdr, Runx2, and of osteoblastic genes but decreased the expression of smooth muscle myosin heavy chain in primary VSMCs cultures. Immunoprecipitation experiments suggested an interaction between Vdr and Runx2. Furthermore, silencing Vdr or Runx2 attenuated the procalcific effects of vitamin D-3. Functional cooperation between Vdr and Runx2 in vascular calcification was also confirmed in in vivo mouse models. Vascular calcification induced by high-dose vitamin D-3 was completely inhibited in Vdr(-/-) or Runx2(+/Delta C) mice, despite elevated levels of serum calcium or alkaline phosphatase. Collectively, these findings suggest that functional cooperation between Vdr and Runx2 is necessary for vascular calcification in response to vitamin D-3.

引用

页数：14

共 52 条

[1] 1,25-dihydroxyvitamin D3/VDR-mediated induction of FGF23 as well as transcriptional control of other bone anabolic and catabolic genes that orchestrate the regulation of phosphate and calcium mineral metabolism [J].