Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Aug 26, 2019; 7(16): 2238-2246
Published online Aug 26, 2019. doi: 10.12998/wjcc.v7.i16.2238
TAZ and myostatin involved in muscle atrophy of congenital neurogenic clubfoot
Jia-Xing Sun, Ze-Yu Yang, Li-Mei Xie, Bing Wang, Ning Bai, Ai-Lu Cai
Jia-Xing Sun, Ze-Yu Yang, Li-Mei Xie, Bing Wang, Ai-Lu Cai, Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
Ning Bai, Key Laboratory of Medical Cell Biology, Ministry of Education; Institute of Translational Medicine, China Medical University, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, Shenyang 110004, Liaoning Province, China
Author contributions: Sun JX, Yang ZY, and Cai AL designed research; Sun JX, Xie LM, and Wang B performed clinical ultrasound examination; Sun JX and Bai N performed the biological experiments; Sun JX and Yang ZY analyzed data; and Sun JX, Yang ZY, and Cai AL wrote the paper.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Shengjing Hospital of China Medical University.
Informed consent statement: The clinical data used in this study were anonymous.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ai-Lu Cai, MD, PhD, Professor, Department of Ultrasound, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Shenyang 110004, Liaoning Province, China. caial1224@sina.com
Telephone: +86-24-9661574194
Received: April 25, 2019
Peer-review started: May 7, 2019
First decision: May 31, 2019
Revised: June 23, 2019
Accepted: July 27, 2019
Article in press: July 27, 2019
Published online: August 26, 2019
Processing time: 123 Days and 17.9 Hours
ARTICLE HIGHLIGHTS
Research background

Muscle atrophy and volume reduction in neurogenic congenital clubfoot are the main factors causing limb mobility disorder, which seriously affects the quality of life of children. The rehabilitation treatment of muscle atrophy has great significance. At present, there are few reports on the study of clubfoot muscle atrophy. Therefore, it is of great clinical significance to use effective methods to diagnose and study in-depth mechanism research of clubfoot muscle atrophy.

Research motivation

Until now, the diagnose of clubfoot muscle atrophy is mainly depended on magnetic resonance imaging. Ultrasound is simple and real-time, and it is more suitable for follow-up prenatal observation and postnatal treatment. Therefore, this study clarifies the diagnostic value of 3D tomographic ultrasound imaging (TUI) for neurogenic congenital clubfoot muscle atrophy. There is no targeted drug treatment for clubfoot muscle atrophy currently, so this study attempts to reveal the mechanism of TAZ involvement in clubfoot muscle atrophy and to find drug therapeutic targets.

Research objectives

The objective of this study was to establish an ultrasound evaluation system for clubfoot muscle atrophy and to reveal the possible mechanisms of TAZ and myostatin involvement in clubfoot muscle atrophy and provide a theoretical basis for the development of potential drug therapy.

Research methods

Prenatal 2D and 3D ultrasound imaging was used to diagnose fetuses with neurological clubfoot. Quantitative evaluation of muscle atrophy was performed by 3D TUI. Muscle specimens were obtained, and protein expression was determined by western blotting and immunostaining. TAZ overexpressed C2C12 cells were differentiated and treated with myostatin, muscle differentiation of each group was compared quantitatively, and the Akt/FOXO4 signaling pathway expression was detected by western blotting.

Research results

The 3D TUI can detect the muscle atrophy on the varus side, which is significantly smaller than the contralateral side. In the gastrocnemius specimens, TAZ and myostatin had opposite expression trends and were negatively correlated. Myostatin inhibited C2C12 muscle differentiation, manifested as thinner myotubes, and was rescued by TAZ overexpression. Overexpressed TAZ reduces the increased p-Akt and FOXO4 expression caused by myostatin.

Research conclusions

The 3D TUI technology can be used to evaluate neurogenic clubfoot muscle atrophy. TAZ and myostatin expression are negatively correlated in muscle samples. TAZ antagonizes muscle differentiation inhibition induced by myostatin, and the mechanism may potentially work through repression of the Akt/FOXO4 signaling pathway.

Research perspectives

Using 3D ultrasound to evaluate the clubfoot muscle atrophy prenatally and postpartum is effective. Appling previously developed TAZ activators for future research in order to develop new drug therapy of clubfoot muscle atrophy is necessary.