Autor: |
Kostyuk SV; Research Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, Russia., Proskurnina EV; Research Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, Russia., Ershova ES; Research Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, Russia., Kameneva LV; Research Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, Russia., Malinovskaya EM; Research Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, Russia., Savinova EA; Research Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, Russia., Sergeeva VA; Research Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, Russia., Umriukhin PE; Research Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, Russia.; Department of Normal Physiology, I.M. Sechenov First Moscow State Medical University (Sechenov University) , Mohovaya Str. 11-4, 125009 Moscow, Russia., Dolgikh OA; Research Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, Russia., Khakina EA; A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavylova St. 28, B-334, 119991 Moscow, Russia., Kraevaya OA; Institute of Problems of Chemical Physics of Russian Academy of Sciences, Semenov Prospect 1, 142432 Chernogolovka (Moscow Region), Russia., Troshin PA; Institute of Problems of Chemical Physics of Russian Academy of Sciences, Semenov Prospect 1, 142432 Chernogolovka (Moscow Region), Russia., Kutsev SI; Research Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, Russia., Veiko NN; Research Centre for Medical Genetics, ul. Moskvorechye 1, 115522 Moscow, Russia. |
Abstrakt: |
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 60 fullerene derivatives on the expression of myogenic transcription factors and myogenic differentiation of human mesenchymal stem cells (MSCs). Uptake of the phosphonate C 60 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 60 pentaphoshonate potassium salt promoted their differentiation towards the myogenic lineage. The transcription factors and gene expressions determining myogenic differentiation ( MYOD1 , MYOG , MYF5 , and MRF4 ) increased, while the expression of osteogenic differentiation factors ( BMP2 , BMP4 , RUNX2 , SPP1 , and OCN ) and adipogenic differentiation factors ( CEBPB , LPL , and AP2 ( FABP4 )) 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. |