Retained differentiation capacity of human skeletal muscle satellite cells from spinal cord-injured individuals.

Mladen Savikj,Emil Kostovski,Maxwell A Ruby,Ulrika Widegren,Juleen R Zierath,Anna Krook,Per O Iversen

doi:10.14814/phy2.13739

Abstract

Despite the well‐known role of satellite cells in skeletal muscle plasticity, the effect of spinal cord injury on their function in humans remains unknown. We determined whether spinal cord injury affects the intrinsic ability of satellite cells to differentiate and produce metabolically healthy myotubes. We obtained vastus lateralis biopsies from eight spinal cord‐injured and six able‐bodied individuals. Satellite cells were isolated, grown and differentiated in vitro. Gene expression was measured by quantitative PCR. Abundance of differentiation markers and regulatory proteins was determined by Western blotting. Protein synthesis and fatty acid oxidation were measured by radioactive tracer‐based assays. Activated satellite cells (myoblasts) and differentiated myotubes derived from skeletal muscle of able‐bodied and spinal cord‐injured individuals expressed similar (P > 0.05) mRNA levels of myogenic regulatory factors. Myogenic differentiation factor 1 expression was higher in myoblasts from spinal cord‐injured individuals. Desmin and myogenin protein content was increased upon differentiation in both groups, while myotubes from spinal cord‐injured individuals contained more type I and II myosin heavy chain. Phosphorylated and total protein levels of Akt‐mechanistic target of rapamycin and forkhead box protein O signalling axes and protein synthesis rate in myotubes were similar (P > 0.05) between groups. Additionally, fatty acid oxidation of myotubes from spinal cord‐injured individuals was unchanged (P > 0.05) compared to able‐bodied controls. Our results indicate that the intrinsic differentiation capacity of satellite cells and metabolic characteristics of myotubes are preserved following spinal cord injury. This may inform potential interventions targeting satellite cell activation to alleviate skeletal muscle atrophy.

Highlights

Traumatic spinal cord injury has a prevalence of between 250 and 906 cases per million in developed countries (Singh et al 2014), and leads to severe physical and psychosocial consequences
The decrease in muscle mass is attributed to an imbalance between protein synthesis and degradation, with associated changes in the protein kinase B (Akt) – mechanistic target of rapamycin signalling axis, and activity of the forkhead box protein O (FoxO) transcription factors and their targets, respectively (Jackman and Kandarian 2004; Dreyer et al 2008; Leger et al 2009)
Satellite cells play an important role in skeletal muscle regeneration and plasticity (Schiaffino et al 1976; Collins et al 2005; Bruusgaard et al 2010; Lepper et al 2011)

Summary

Introduction

Traumatic spinal cord injury has a prevalence of between 250 and 906 cases per million in developed countries (Singh et al 2014), and leads to severe physical and psychosocial consequences. It is characterized by varying degrees of motor, sensory and autonomic neurological deficits below the level of injury, affecting most bodily a 2018 The Authors. The reduced muscle mass diminishes peripheral glucose disposal (Aksnes et al 1996). Impairments in both lipid and glucose metabolism increase the risk of noncommunicable diseases such as type 2 diabetes and cardiovascular disease (Cragg et al 2013a,b)

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