Related Experiment Video
Updated: May 1, 2026

Protein Isolation from the Developing Embryonic Mouse Heart Valve Region
Published on: September 23, 2014
Twist-related protein 1 negatively regulated osteoblastic transdifferentiation of human aortic valve interstitial
Xi-Wu Zhang1, Bo-Yao Zhang1, Shu-Wei Wang2
1Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
Objective:
Valve calcification involves transdifferentiation of valve interstitial cells (VICs) into osteoblasts. Twist-related protein 1 (TWIST1) has been established as a negative regulator of osteoblast differentiation in both mouse and human mesenchymal stem cells, but its function in human aortic VICs is unknown. In our study, we determined the mechanism of TWIST1 action in regulating osteoblastic transdifferentiation of human aortic VICs.
Methods:
Human calcified and noncalcified aortic valves were examined for TWIST1 expression. Human aortic VICs were isolated and cultured.
Results:
The data showed that calcified aortic valves express lower levels of TWIST1. In vitro experiments showed that TWIST1 overexpression inhibited the transdifferentiation of VICs into osteoblasts by decreasing the expression of runt-related transcription factor 2 (RUNX2) and its downstream osteoblastic markers. Through chromatin immunoprecipitation and dual luciferase assays, we found that TWIST1 repressed the expression of RUNX2 by directly binding to an E-box located at -820 bp of the RUNX2 P2 promoter region and inhibiting its activity.
Conclusions:
Our study results suggest that TWIST1 could play an important role in preventing human aortic valve calcification by negatively regulating osteoblastic transdifferentiation of human aortic VICs through direct inhibition of RUNX2.
More Related Videos
Related Concept Videos
TGF - β Signaling Pathway
Regulation of Angiogenesis and Blood Supply
Canonical Wnt Signaling Pathway
Negative Regulator Molecules
Non-Canonical Wnt Signaling Pathways
Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

