Abstract
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 C60 fullerene derivatives on the expression of myogenic transcription factors and myogenic differentiation of human mesenchymal stem cells (MSCs). Uptake of the phosphonate C60 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 C60 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.
Highlights
Recovery of muscle tissue damaged by diseases or injuries is a complex process
The effect of three phosphorus-containing water-soluble derivatives of C60 fullerene on mesenchymal stem cells (MSCs) obtained from different donors was studied
We have previously shown that aqueous solutions of C60 derivatives exhibit dark-red fluorescence in the range of 600–950 nm excited by a wide wavelength range [40,41,42], which makes it possible to analyze their distribution in cells
Summary
Recovery of muscle tissue damaged by diseases or injuries is a complex process. Muscle weakness, muscular dystrophy, and impaired physical mobility are characteristic of genetically heterogeneous myodystrophies such as Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy [2]. Pathogenic variations in the dystrophin gene underlie. This disease is the most common childhood muscular dystrophy, affecting 1:5000 live male births [3]. Facioscapulohumeral muscular dystrophy is the second most prevalent dystrophy after Duchenne muscular dystrophy, and affects approximately 870,000 people worldwide [4]. Facioscapulohumeral muscular dystrophy results from the inappropriate expression of a gene called Double Homeobox 4 (DUX4) [5]. Congenital myotonic dystrophy is an autosomal dominant genetic disorder with an incidence of approx
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