PMID- 24349534
OWN - NLM
STAT- MEDLINE
DCOM- 20140929
LR  - 20220316
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 12
DP  - 2013
TI  - Functional cooperation between vitamin D receptor and Runx2 in vitamin D-induced 
      vascular calcification.
PG  - e83584
LID - 10.1371/journal.pone.0083584 [doi]
LID - e83584
AB  - 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 D3 using in vitro VSMCs cultures and in vivo in 
      Vdr knockout (Vdr(-/-)) and Runx2 carboxy-terminus truncated heterozygous 
      (Runx2(+/DeltaC)) mice. Treatment of VSMCs with active vitamin D3 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 D3. Functional cooperation between Vdr and 
      Runx2 in vascular calcification was also confirmed in in vivo mouse models. 
      Vascular calcification induced by high-dose vitamin D3 was completely inhibited 
      in Vdr(-/-) or Runx2(+/DeltaC) 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 D3.
FAU - Han, Min-Su
AU  - Han MS
AD  - Department of Biochemistry and Cell Biology, WCU and BK21 plus programs, CMRC, 
      Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National 
      University, Daegu, Republic of Korea.
FAU - Che, Xiangguo
AU  - Che X
AD  - Department of Biochemistry and Cell Biology, WCU and BK21 plus programs, CMRC, 
      Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National 
      University, Daegu, Republic of Korea.
FAU - Cho, Gyoung-ho
AU  - Cho GH
AD  - Department of Biochemistry and Cell Biology, WCU and BK21 plus programs, CMRC, 
      Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National 
      University, Daegu, Republic of Korea.
FAU - Park, Hye-Ri
AU  - Park HR
AD  - Department of Biochemistry and Cell Biology, WCU and BK21 plus programs, CMRC, 
      Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National 
      University, Daegu, Republic of Korea.
FAU - Lim, Kyung-Eun
AU  - Lim KE
AD  - Department of Biochemistry and Cell Biology, WCU and BK21 plus programs, CMRC, 
      Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National 
      University, Daegu, Republic of Korea.
FAU - Park, Na-Rae
AU  - Park NR
AD  - Department of Biochemistry and Cell Biology, WCU and BK21 plus programs, CMRC, 
      Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National 
      University, Daegu, Republic of Korea.
FAU - Jin, Jung-Sook
AU  - Jin JS
AD  - Department of Biochemistry and Cell Biology, WCU and BK21 plus programs, CMRC, 
      Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National 
      University, Daegu, Republic of Korea.
FAU - Jung, Youn-Kwan
AU  - Jung YK
AD  - Department of Biochemistry and Cell Biology, WCU and BK21 plus programs, CMRC, 
      Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National 
      University, Daegu, Republic of Korea.
FAU - Jeong, Jae-Hwan
AU  - Jeong JH
AD  - Department of Biochemistry and Cell Biology, WCU and BK21 plus programs, CMRC, 
      Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National 
      University, Daegu, Republic of Korea.
FAU - Lee, In-Kyu
AU  - Lee IK
AD  - Department of Internal Medicine, Division of Endocrinology, School of Medicine, 
      Kyungpook National University, Daegu, Republic of Korea.
FAU - Kato, Shigeaki
AU  - Kato S
AD  - Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, 
      Japan.
FAU - Choi, Je-Yong
AU  - Choi JY
AD  - Department of Biochemistry and Cell Biology, WCU and BK21 plus programs, CMRC, 
      Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National 
      University, Daegu, Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131212
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Runx2 protein, mouse)
RN  - 0 (Runx2 protein, rat)
RN  - 1C6V77QF41 (Cholecalciferol)
SB  - IM
MH  - Animals
MH  - Bone Density Conservation Agents/*adverse effects/pharmacology
MH  - Cells, Cultured
MH  - Cholecalciferol/*adverse effects/pharmacology
MH  - Core Binding Factor Alpha 1 Subunit/genetics/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Muscle, Smooth, Vascular/*metabolism/pathology
MH  - Myocytes, Smooth Muscle/*metabolism/pathology
MH  - Rats
MH  - Receptors, Calcitriol/genetics/*metabolism
MH  - *Vascular Calcification/chemically induced/genetics/metabolism/pathology
PMC - PMC3861528
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/12/19 06:00
MHDA- 2014/09/30 06:00
PMCR- 2013/12/12
CRDT- 2013/12/19 06:00
PHST- 2013/07/07 00:00 [received]
PHST- 2013/11/06 00:00 [accepted]
PHST- 2013/12/19 06:00 [entrez]
PHST- 2013/12/19 06:00 [pubmed]
PHST- 2014/09/30 06:00 [medline]
PHST- 2013/12/12 00:00 [pmc-release]
AID - PONE-D-13-28013 [pii]
AID - 10.1371/journal.pone.0083584 [doi]
PST - epublish
SO  - PLoS One. 2013 Dec 12;8(12):e83584. doi: 10.1371/journal.pone.0083584. 
      eCollection 2013.