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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2021-08-01
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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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