PMID- 23644099
OWN - NLM
STAT- MEDLINE
DCOM- 20131024
LR  - 20191210
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 183
IP  - 1
DP  - 2013 Jul
TI  - Functional interaction of osteogenic transcription factors Runx2 and Vdr in 
      transcriptional regulation of Opn during soft tissue calcification.
PG  - 60-8
LID - S0002-9440(13)00263-0 [pii]
LID - 10.1016/j.ajpath.2013.03.007 [doi]
AB  - Loss of Abcc6 gene expression was identified to be responsible for dystrophic 
      calcification of the heart (DCC) or vessels after acute injury in several strains 
      of laboratory mice. This calcification shares features with osteogenesis and may 
      involve osteogenic factors. Tissue expression of osteopontin (Opn) and 11 
      osteogenic transcription factors were studied in vivo in mouse models for DCC and 
      in vitro using luciferase reporter gene assays. Compared with DCC-resistant 
      C57BL/6 mice, a significant increase in Opn transcription was demonstrated in 
      necrotic lesions of both DCC-susceptible C3H/He and B6.C3H(Dyscalc1) congenic 
      mice at day 3 after injury. Significant increases in gene expression were also 
      demonstrated for the transcription factors runt domain-containing transcription 
      factor 2 (Runx2), vitamin D receptor (Vdr), SRY (sex-determining region Y)-box 9 
      protein, and Nfkb1 in C3H/He mice versus C57BL/6 controls. However, only Runx2 
      remained significantly increased in the B6.C3H(Dyscalc1) congenic mice, which 
      carry only the Dyscalc1 locus with functional Abcc6 deletion on a C57BL/6 genetic 
      background. Luciferase assay use increased Opn promoter activity, which was 
      demonstrated after overexpression of Runx2. A poly-T stretch insertion was 
      identified to stabilize the binding of Runx2, thus significantly enhancing Opn 
      promoter activity. This Runx2-mediated activation was further enhanced by 
      cotransfection with Vdr. Our data suggest a key role of Runx2 in the regulation 
      of Opn in a model of cardiovascular calcification and demonstrate a synergistic 
      cooperation of Runx2 and Vdr.
CI  - Copyright (c) 2013 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Sowa, Ann-Kathrin
AU  - Sowa AK
AD  - Institute for Integrative and Experimental Genomics and DZHK-German Centre for 
      Cardiovascular Research, partner site Lubeck/Hamburg/Kiel, University of Lubeck, 
      Lubeck, Germany.
FAU - Kaiser, Frank J
AU  - Kaiser FJ
FAU - Eckhold, Juliane
AU  - Eckhold J
FAU - Kessler, Thorsten
AU  - Kessler T
FAU - Aherrahrou, Redouane
AU  - Aherrahrou R
FAU - Wrobel, Sandra
AU  - Wrobel S
FAU - Kaczmarek, Piotr M
AU  - Kaczmarek PM
FAU - Doehring, Lars
AU  - Doehring L
FAU - Schunkert, Heribert
AU  - Schunkert H
FAU - Erdmann, Jeanette
AU  - Erdmann J
FAU - Aherrahrou, Zouhair
AU  - Aherrahrou Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130502
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Abcc6 protein, mouse)
RN  - 0 (Biomarkers)
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Runx2 protein, mouse)
RN  - 0 (Spp1 protein, mouse)
RN  - 106441-73-0 (Osteopontin)
SB  - IM
MH  - ATP-Binding Cassette Transporters/deficiency
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Blotting, Western
MH  - Core Binding Factor Alpha 1 Subunit/*metabolism
MH  - Female
MH  - Immunohistochemistry
MH  - Luminescent Measurements
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Multidrug Resistance-Associated Proteins
MH  - Osteopontin/*metabolism
MH  - Receptors, Calcitriol/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Vascular Calcification/*metabolism
EDAT- 2013/05/07 06:00
MHDA- 2013/10/25 06:00
CRDT- 2013/05/07 06:00
PHST- 2012/06/22 00:00 [received]
PHST- 2013/03/11 00:00 [revised]
PHST- 2013/03/12 00:00 [accepted]
PHST- 2013/05/07 06:00 [entrez]
PHST- 2013/05/07 06:00 [pubmed]
PHST- 2013/10/25 06:00 [medline]
AID - S0002-9440(13)00263-0 [pii]
AID - 10.1016/j.ajpath.2013.03.007 [doi]
PST - ppublish
SO  - Am J Pathol. 2013 Jul;183(1):60-8. doi: 10.1016/j.ajpath.2013.03.007. Epub 2013 
      May 2.