Functional Cooperation Between Vitamin D Receptor and Runx2 in Vitamin D-induced Vascular Calcification

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Dec 19

PMID 24349534

Citations 24

Authors

Min-Su Han

Xiangguo Che

Gyoung-Ho Cho

Hye-Ri Park

Kyung-Eun Lim

Na-Rae Park

Jung-Sook Jin

Youn-Kwan Jung

Jae-Hwan Jeong

In-Kyu Lee

Shigeaki Kato

Je-Yong Choi

Affiliations

Soon will be listed here.

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.

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