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
Abstract
BACKGROUND

Muscular atrophy is the basic defect of neurogenic clubfoot. Muscle atrophy of clubfoot needs more scientific and reasonable imaging measurement parameters to evaluate. The Hippo pathway and myostatin pathway may be directly correlated in myogenesis. In this study, we will use congenital neurogenic clubfoot muscle atrophy model to verify in vivo. Further, the antagonistic mechanism of TAZ on myostatin was studied in the C2C12 cell differentiation model.

AIM

To identify muscle atrophy in fetal neurogenic clubfoot by ultrasound imaging and detect the expression of TAZ and myostatin in gastrocnemius muscle. To elucidate the possible mechanisms by which TAZ antagonizes myostatin-induced atrophy in an in vitro cell model.

METHODS

Muscle atrophy in eight cases of fetal unilateral clubfoot with nervous system abnormalities was identified by 2D and 3D ultrasound. Western blotting and immunostaining were performed to detect expression of myostatin and TAZ. TAZ overexpression in C2C12 myotubes and the expression of associated proteins were analyzed by western blotting.

RESULTS

The maximum cross-sectional area of the fetal clubfoot on the varus side was reduced compared to the contralateral side. Myostatin was elevated in the atrophied gastrocnemius muscle, while TAZ expression was decreased. They were negatively correlated. TAZ overexpression reversed the diameter reduction of the myotube, downregulated phosphorylated Akt, and increased the expression of forkhead box O4 induced by myostatin.

CONCLUSION

Ultrasound can detect muscle atrophy of fetal clubfoot. TAZ and myostatin are involved in the pathological process of neurogenic clubfoot muscle atrophy. TAZ antagonizes myostatin-induced myotube atrophy, potentially through regulation of the Akt/forkhead box O4 signaling pathway.

Keywords: Congenital clubfoot; Neurogenic; Muscle atrophy; Myostatin; TAZ

Core tip: This study aimed to identify muscle atrophy in fetal neurogenic clubfoot, detect expression of TAZ and myostatin in gastrocnemius muscle, and establish the mechanisms through which TAZ antagonizes myostatin-induced atrophy in an in vitro cell model. Muscle atrophy in fetal unilateral clubfoot with nervous system abnormalities was identified by ultrasound. TAZ overexpression in C2C12 myotubes induced atrophy by myostatin. Both TAZ and myostatin are involved in the process of neurogenic clubfoot muscle atrophy, and they are negatively correlated. TAZ antagonizes myostatin-induced myotube atrophy, potentially through regulation of the Akt/forkhead box O4 pathway.