Functional cooperation between vitamin D receptor and Runx2 in vitamin D-induced vascular calcification

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...

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Veröffentlicht in:PloS one 2013-12, Vol.8 (12), p.e83584
Hauptverfasser: Han, Min-Su, Che, Xiangguo, Cho, Gyoung-ho, Park, Hye-Ri, Lim, Kyung-Eun, Park, Na-Rae, Jin, Jung-Sook, Jung, Youn-Kwan, Jeong, Jae-Hwan, Lee, In-Kyu, Kato, Shigeaki, Choi, Je-Yong
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creator Han, Min-Su
Che, Xiangguo
Cho, Gyoung-ho
Park, Hye-Ri
Lim, Kyung-Eun
Park, Na-Rae
Jin, Jung-Sook
Jung, Youn-Kwan
Jeong, Jae-Hwan
Lee, In-Kyu
Kato, Shigeaki
Choi, Je-Yong
description 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(+/ΔC)) 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(+/ΔC) 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.
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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(+/ΔC)) 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. 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chemically induced</subject><subject>Vascular Calcification - genetics</subject><subject>Vascular Calcification - metabolism</subject><subject>Vascular Calcification - pathology</subject><subject>Vitamin D</subject><subject>Vitamin D receptors</subject><subject>Vitamin D3</subject><subject>Vitamin deficiency</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl-L1DAUxYso7rr6DUQLguDDjEmTNumLsKyuDiwsrH9ew216O5Ohk4xJOq7f3sxOd5mCggSa9OZ3Ty-nJ8teUjKnTND3azd4C_186yzOCZGslPxRdkprVsyqgrDHR-eT7FkIa0JKJqvqaXZScMbrkvHTbHk5WB2NS0q5dm6LHvZveYPxF6LNdybCxtj8Y-5R4zY6n4Nt85vB3ha5ObqfGdsOGtt8B0EPPfhcQ69NZ_Sd4PPsSQd9wBfjfpZ9v_z07eLL7Or68-Li_GqmRSnjrNFUMspQA-uAkppWFa8L3pKSaGRSCiFQ1LWoOefpUbWi4aCLrhSlYF1J2Fn2-qC77V1Qo0dBUS64LIWQRSIWB6J1sFZbbzbgfysHRt0VnF8q8NHoHlVNsEEKlSSs4ZwQ6BihbUEKJjuOVZ20PoxfG5oNthpt9NBPRKc31qzU0u1U-g-0LGQSeDMKePdzwBD_MfJILSFNZWznkpjemKDVORfJMCL4fpj5X6i0WtwYnVLSmVSfNLybNCQm4m1cwhCCWny9-X_2-seUfXvErhD6uAquH_Y5CFOQH0DtXQgeuwfnKFH7kN-7ofYhV2PIU9urY9cfmu5Tzf4AWu72cg</recordid><startdate>20131212</startdate><enddate>20131212</enddate><creator>Han, Min-Su</creator><creator>Che, Xiangguo</creator><creator>Cho, Gyoung-ho</creator><creator>Park, Hye-Ri</creator><creator>Lim, Kyung-Eun</creator><creator>Park, Na-Rae</creator><creator>Jin, Jung-Sook</creator><creator>Jung, Youn-Kwan</creator><creator>Jeong, Jae-Hwan</creator><creator>Lee, In-Kyu</creator><creator>Kato, Shigeaki</creator><creator>Choi, Je-Yong</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131212</creationdate><title>Functional cooperation between vitamin D receptor and Runx2 in vitamin D-induced vascular calcification</title><author>Han, Min-Su ; Che, Xiangguo ; Cho, Gyoung-ho ; Park, Hye-Ri ; Lim, Kyung-Eun ; Park, Na-Rae ; Jin, Jung-Sook ; Jung, Youn-Kwan ; Jeong, Jae-Hwan ; Lee, In-Kyu ; Kato, Shigeaki ; Choi, Je-Yong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-bc18313eca3fa1091664924d050ce388777e799794447946d7b4ac2f57573f503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Alkaline phosphatase</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biocompatibility</topic><topic>Biology</topic><topic>Biomedical materials</topic><topic>Bone Density Conservation Agents - 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source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS)
subjects Alkaline phosphatase
Animal models
Animals
Biochemistry
Biocompatibility
Biology
Biomedical materials
Bone Density Conservation Agents - adverse effects
Bone Density Conservation Agents - pharmacology
Calcification
Calcification (ectopic)
Calcification (Physiology)
Calcium
Calcium (blood)
Cbfa-1 protein
Cells, Cultured
Cholecalciferol - adverse effects
Cholecalciferol - pharmacology
Cooperation
Cooperativity
Core Binding Factor Alpha 1 Subunit - genetics
Core Binding Factor Alpha 1 Subunit - metabolism
Endocrinology
Gene expression
Genomes
Growth factors
Homeostasis
Immunoprecipitation
Kidneys
Ligands
Medicine
Mice
Mice, Knockout
Muscle proteins
Muscle, Smooth, Vascular - metabolism
Muscle, Smooth, Vascular - pathology
Muscles
Myocytes, Smooth Muscle - metabolism
Myocytes, Smooth Muscle - pathology
Myosin
Osteoblastogenesis
Osteoblasts
Phosphatases
Polyclonal antibodies
Proteins
Rats
Receptors, Calcitriol - genetics
Receptors, Calcitriol - metabolism
Rodents
Smooth muscle
Transcription factors
Vascular Calcification - chemically induced
Vascular Calcification - genetics
Vascular Calcification - metabolism
Vascular Calcification - pathology
Vitamin D
Vitamin D receptors
Vitamin D3
Vitamin deficiency
title Functional cooperation between vitamin D receptor and Runx2 in vitamin D-induced vascular calcification
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