The Phosphonate Derivative of C<sub>60</sub> Fullerene Induces Differentiation towards the Myogenic Lineage in Human Adipose-Derived Mesenchymal Stem Cells

Inductors of myogenic stem cell differentiation attract attention, as they can be used to treat myodystrophies and post-traumatic injuries. Functionalization of fullerenes makes it possible to obtain water-soluble derivatives with targeted biochemical activity. This study examined the effects of the...

Full description

Bibliographic Details
Main Authors: Svetlana V. Kostyuk, Elena V. Proskurnina, Elizaveta S. Ershova, Larisa V. Kameneva, Elena M. Malinovskaya, Ekaterina A. Savinova, Vasilina A. Sergeeva, Pavel E. Umriukhin, Olga A. Dolgikh, Ekaterina A. Khakina, Olga A. Kraevaya, Pavel A. Troshin, Sergey I. Kutsev, Natalia N. Veiko
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/17/9284
Description
Summary:Inductors of myogenic stem cell differentiation attract attention, as they can be used to treat myodystrophies and post-traumatic injuries. Functionalization of fullerenes makes it possible to obtain water-soluble derivatives with targeted biochemical activity. This study examined the effects of the phosphonate C<sub>60</sub> fullerene derivatives on the expression of myogenic transcription factors and myogenic differentiation of human mesenchymal stem cells (MSCs). Uptake of the phosphonate C<sub>60</sub> fullerene derivatives in human MSCs, intracellular ROS visualization, superoxide scavenging potential, and the expression of myogenic, adipogenic, and osteogenic differentiation genes were studied. The prolonged MSC incubation (within 7–14 days) with the C<sub>60</sub> pentaphoshonate potassium salt promoted their differentiation towards the myogenic lineage. The transcription factors and gene expressions determining myogenic differentiation (<i>MYOD1</i>, <i>MYOG</i>, <i>MYF5</i>, and <i>MRF4</i>) increased, while the expression of osteogenic differentiation factors (<i>BMP2</i>, <i>BMP4</i>, <i>RUNX2</i>, <i>SPP1</i>, and <i>OCN</i>) and adipogenic differentiation factors (<i>CEBPB</i>, <i>LPL</i>, and <i>AP2</i> (<i>FABP4</i>)) was reduced or did not change. The stimulation of autophagy may be one of the factors contributing to the increased expression of myogenic differentiation genes in MSCs. Autophagy may be caused by intracellular alkalosis and/or short-term intracellular oxidative stress.
ISSN:1661-6596
1422-0067