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Article

Heparin-Mimicking Polymer-Based In Vitro Platform Recapitulates In Vivo Muscle Atrophy Phenotypes

1
Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan-si 31151, Korea
2
School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Korea
3
Department of Integrated Biomedical Science, Soonchunhyang University, Asan-si 31538, Korea
4
Department of Pharmaceutical Engineering, Soonchunhyang University, Asan-si 31538, Korea
5
Institute of Tissue Regeneration, Soonchunhyang University, Asan-si 31538, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this study.
Academic Editor: Peter John Jervis
Int. J. Mol. Sci. 2021, 22(5), 2488; https://doi.org/10.3390/ijms22052488
Received: 6 February 2021 / Revised: 25 February 2021 / Accepted: 25 February 2021 / Published: 2 March 2021
(This article belongs to the Special Issue Hydrogels in Regenerative Medicine and Other Biomedical Applications)
The cell–cell/cell–matrix interactions between myoblasts and their extracellular microenvironment have been shown to play a crucial role in the regulation of in vitro myogenic differentiation and in vivo skeletal muscle regeneration. In this study, by harnessing the heparin-mimicking polymer, poly(sodium-4-styrenesulfonate) (PSS), which has a negatively charged surface, we engineered an in vitro cell culture platform for the purpose of recapitulating in vivo muscle atrophy-like phenotypes. Our initial findings showed that heparin-mimicking moieties inhibited the fusion of mononucleated myoblasts into multinucleated myotubes, as indicated by the decreased gene and protein expression levels of myogenic factors, myotube fusion-related markers, and focal adhesion kinase (FAK). We further elucidated the underlying molecular mechanism via transcriptome analyses, observing that the insulin/PI3K/mTOR and Wnt signaling pathways were significantly downregulated by heparin-mimicking moieties through the inhibition of FAK/Cav3. Taken together, the easy-to-adapt heparin-mimicking polymer-based in vitro cell culture platform could be an attractive platform for potential applications in drug screening, providing clear readouts of changes in insulin/PI3K/mTOR and Wnt signaling pathways. View Full-Text
Keywords: synthetic mimic of heparin; poly(sodium-4-styrenesulfonate); myoblast; myogenic differentiation; fusion; focal adhesion kinase (FAK) synthetic mimic of heparin; poly(sodium-4-styrenesulfonate); myoblast; myogenic differentiation; fusion; focal adhesion kinase (FAK)
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MDPI and ACS Style

Kim, H.; Jeong, J.H.; Fendereski, M.; Lee, H.-S.; Kang, D.Y.; Hur, S.S.; Amirian, J.; Kim, Y.; Pham, N.T.; Suh, N.; Hwang, N.S.-Y.; Ryu, S.; Yoon, J.K.; Hwang, Y. Heparin-Mimicking Polymer-Based In Vitro Platform Recapitulates In Vivo Muscle Atrophy Phenotypes. Int. J. Mol. Sci. 2021, 22, 2488. https://doi.org/10.3390/ijms22052488

AMA Style

Kim H, Jeong JH, Fendereski M, Lee H-S, Kang DY, Hur SS, Amirian J, Kim Y, Pham NT, Suh N, Hwang NS-Y, Ryu S, Yoon JK, Hwang Y. Heparin-Mimicking Polymer-Based In Vitro Platform Recapitulates In Vivo Muscle Atrophy Phenotypes. International Journal of Molecular Sciences. 2021; 22(5):2488. https://doi.org/10.3390/ijms22052488

Chicago/Turabian Style

Kim, Hyunbum, Ji H. Jeong, Mona Fendereski, Hyo-Shin Lee, Da Y. Kang, Sung S. Hur, Jhaleh Amirian, Yunhye Kim, Nghia T. Pham, Nayoung Suh, Nathaniel S.-Y. Hwang, Seongho Ryu, Jeong K. Yoon, and Yongsung Hwang. 2021. "Heparin-Mimicking Polymer-Based In Vitro Platform Recapitulates In Vivo Muscle Atrophy Phenotypes" International Journal of Molecular Sciences 22, no. 5: 2488. https://doi.org/10.3390/ijms22052488

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