The Essential Role of Stathmin in Myoblast C2C12 for Vertical Vibration-Induced Myotube Formation.

Yi-Hsiung Lin,Liang-Yin Chou,Chung-Hwan Chen,Hsin-Chiao Chou,Tsung-Lin Cheng,Chau-Zen Wang,Lin Kang

doi:10.3390/biom11111583

Abstract

Vertical vibration (VV) is a type of whole body vibration, which induces muscle contraction through vibration to improve muscle strength and bone density. However, the mechanism of VV on muscle cell myotube formation is still unclear. In the current study, we aim to clarify the mechanism involved in VV’s stimulation of myotube formation. In order to identify the molecules regulated by VV, we performed proteomics analysis including 2D electrophoresis combined with MALDI-TOF/TOF Mass. Stathmin was identified as a high potential molecule responding to VV stimulation, and we found that under VV stimulation, the expression of stathmin gene and protein increased in a time-dependent manner. In addition, we also confirmed that the increase of stathmin stimulated by VV is mediated through the PI3K/Akt pathway. Furthermore, stathmin siRNA significantly down-regulated the expression of myogenic regulatory factor (MRF) MyoD, decorin, and type I collagen (Col-I), and down-regulated the cellular process regulators such as FGF7, TGFBr1 and PAK3. Taken together, our results confirm that under the stimulation of VV, PI3K/Akt and stathmin would be activated, as well as the up-regulation of MRFs, such as FGF7, TGFBr1 and PAK3 to initiate myogenesis. It also showed that the response of MRF to VV stimulation was significantly related to stathmin expression, which also confirmed the importance of stathmin in the entire myotube formation process. This study may provide evidence of stathmin as a biological indicator of VV to increase muscle strength.

Highlights

Whole-body vibration (WBV) exercise is a mechanical load that has recently been widely used as a means of physical therapy [1]
We found that the mechanism by which Vertical vibration (VV) induced C2C12 cells to form myotubes had three different manners: (1) the activation of the Phosphoinositide 3-kinases (PI3K)/Akt pathway by increasing its phosphorylation status; (2) the upregulation of stathmin; and (3) the activation of myogenic regulatory factor (MRF), Fibroblast Growth Factor 7 (FGF7), TGFBr1 and P21 Activated Kinase 3 (PAK3) in response to VV-stimulated myotube formation
In addition to the expression of regulatory factors related to myotube formation, we studied the regulatory molecules involved in VV effect, including TGFBr1, FGF7 and PAK3, and discussed the regulatory role of stathmin on these molecules in the process of VV-induced C2C12 differentiation

Summary

Introduction

Whole-body vibration (WBV) exercise is a mechanical load that has recently been widely used as a means of physical therapy [1]. Recent studies have demonstrated that the prolonged application of WBV exercise can improve muscle strength and power, body balance and mobility [2,3], especially for athletes or individuals in the absence of gravity, healthy elderly individuals, young adults, and untrained adults to maintain muscle performance [4,5,6]. Vertical vibration (VV) is a type of WBV that can be performed at home, reducing both the therapeutic cost and traveling time of patients [7]. The detailed mechanisms of VV-induced myotube formation remain undefined

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