title: Functional cooperation between vitamin D receptor and Runx2 in vitamin D-induced vascular calcification.
abstract: 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.
authors.affiliation: 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.
authors.forename: Min-Su
authors.initials: MS
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Che
authors.affiliation: 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.
authors.forename: Gyoung-ho
authors.initials: GH
authors.lastname: Cho
authors.affiliation: 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.
authors.forename: Hye-Ri
authors.initials: HR
authors.lastname: Park
authors.affiliation: 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.
authors.forename: Kyung-Eun
authors.initials: KE
authors.lastname: Lim
authors.affiliation: 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.
authors.forename: Na-Rae
authors.initials: NR
authors.lastname: Park
authors.affiliation: 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.
authors.forename: Jung-Sook
authors.initials: JS
authors.lastname: Jin
authors.affiliation: 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.
authors.forename: Youn-Kwan
authors.initials: YK
authors.lastname: Jung
authors.affiliation: 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.
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
authors.affiliation: 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.
authors.forename: Je-Yong
authors.initials: JY
authors.lastname: Choi
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000494:pharmacology; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000009:adverse effects* / Q000494:pharmacology; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D061205:Vascular Calcification / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D050071:Bone Density Conservation Agents; D050659:Core Binding Factor Alpha 1 Subunit; D018167:Receptors, Calcitriol; C493716:Runx2 protein, mouse; C493717:Runx2 protein, rat; D002762:Cholecalciferol