Applying exercise-mimetic engineered skeletal muscle model to interrogate the adaptive response of irisin to mechanical force

Yuwei Zhang; Lizhen Wang; Hongyan Kang; Chia-Ying Lin; Yubo Fan

doi:10.1016/j.isci.2022.104135

Applying exercise-mimetic engineered skeletal muscle model to interrogate the adaptive response of irisin to mechanical force

iScience. 2022 Mar 23;25(4):104135. doi: 10.1016/j.isci.2022.104135. eCollection 2022 Apr 15.

Authors

Yuwei Zhang¹, Lizhen Wang¹, Hongyan Kang¹, Chia-Ying Lin^{1

2

3

4}, Yubo Fan^{1

5}

Affiliations

¹ Key laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.
² Department of Biomedical, Chemical & Environmental Engineering, University of Cincinnati, Cincinnati, USA.
³ Department of Orthopaedic Surgery, University of Cincinnati, Cincinnati, USA.
⁴ Department of Neurosurgery, University of Cincinnati, Cincinnati, USA.
⁵ School of Engineering Medicine, Beihang University, Beijing 100083, China.

Abstract

Physical exercise induces the secretion of irisin from contractile muscle into circulation; however, the adaptive response of irisin to mechanical stimulus in skeletal muscle in vitro remains numerously unknown. In an effort to investigate whether irisin is inducible in vitro, we developed a bioreactor consisting of a retractable mechanical force controller and a conditional tissue culture system. Upon this model, a distinguished surge of irisin was detected in stretched myotubes as cyclic strain initiated, and the surge was able to be stalled by knocking out FNDC5. Intriguingly, increased irisin secretory is associated with the shifts of MyHC isoforms from anaerobic type to aerobic type in myotubes. We further revealed that PGC-1α1 and PGC-1α4 mRNAs expression, rather than PGC-1α2 and PGC-1α3, contributed to the generation of irisin in myotubes during cyclic strain. Lastly, combined with co-culturing MC3T3 osteoblasts, we demonstrated the bioactivity of generated irisin, promoting the osteogenic differentiation.

Keywords: Biological sciences; Cell biology; Molecular biology.