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...

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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
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author 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
author_facet 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
author_sort Svetlana V. Kostyuk
collection DOAJ
description 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.
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spelling doaj.art-90c853b267064913b2151f8e98a31ee72023-11-22T10:40:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012217928410.3390/ijms22179284The Phosphonate Derivative of C<sub>60</sub> Fullerene Induces Differentiation towards the Myogenic Lineage in Human Adipose-Derived Mesenchymal Stem CellsSvetlana V. Kostyuk0Elena V. Proskurnina1Elizaveta S. Ershova2Larisa V. Kameneva3Elena M. Malinovskaya4Ekaterina A. Savinova5Vasilina A. Sergeeva6Pavel E. Umriukhin7Olga A. Dolgikh8Ekaterina A. Khakina9Olga A. Kraevaya10Pavel A. Troshin11Sergey I. Kutsev12Natalia N. Veiko13Research Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, RussiaA.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavylova St. 28, B-334, 119991 Moscow, RussiaInstitute of Problems of Chemical Physics of Russian Academy of Sciences, Semenov Prospect 1, 142432 Chernogolovka (Moscow Region), RussiaInstitute of Problems of Chemical Physics of Russian Academy of Sciences, Semenov Prospect 1, 142432 Chernogolovka (Moscow Region), RussiaResearch Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, RussiaInductors 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.https://www.mdpi.com/1422-0067/22/17/9284mesenchymal stem cellsfullerene phosphonate derivativesmyogenic differentiationautophagyreactive oxygen species
spellingShingle 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
The Phosphonate Derivative of C<sub>60</sub> Fullerene Induces Differentiation towards the Myogenic Lineage in Human Adipose-Derived Mesenchymal Stem Cells
International Journal of Molecular Sciences
mesenchymal stem cells
fullerene phosphonate derivatives
myogenic differentiation
autophagy
reactive oxygen species
title The Phosphonate Derivative of C<sub>60</sub> Fullerene Induces Differentiation towards the Myogenic Lineage in Human Adipose-Derived Mesenchymal Stem Cells
title_full The Phosphonate Derivative of C<sub>60</sub> Fullerene Induces Differentiation towards the Myogenic Lineage in Human Adipose-Derived Mesenchymal Stem Cells
title_fullStr The Phosphonate Derivative of C<sub>60</sub> Fullerene Induces Differentiation towards the Myogenic Lineage in Human Adipose-Derived Mesenchymal Stem Cells
title_full_unstemmed The Phosphonate Derivative of C<sub>60</sub> Fullerene Induces Differentiation towards the Myogenic Lineage in Human Adipose-Derived Mesenchymal Stem Cells
title_short The Phosphonate Derivative of C<sub>60</sub> Fullerene Induces Differentiation towards the Myogenic Lineage in Human Adipose-Derived Mesenchymal Stem Cells
title_sort phosphonate derivative of c sub 60 sub fullerene induces differentiation towards the myogenic lineage in human adipose derived mesenchymal stem cells
topic mesenchymal stem cells
fullerene phosphonate derivatives
myogenic differentiation
autophagy
reactive oxygen species
url https://www.mdpi.com/1422-0067/22/17/9284
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