Growth Factors Do Not Improve Muscle Function in Young or Adult mdx Mice

Abstract

Hepatocyte growth factor; Leukemia inhibitory factor; Muscular regeneration

Factor de crecimiento de los hepatocitos; Factor inhibidor de la leucemia; Regeneración muscular

Factor de creixement dels hepatòcits; Factor inhibidor de la leucèmia; Regeneració muscular

Muscular dystrophies constitute a broad group of genetic disorders leading to muscle wasting. We have previously demonstrated that treating a muscular atrophy mouse model with growth factors resulted in increased muscle mass. In the present study, we treated the Duchenne mouse model mdx for 12 weeks with myogenic growth factors peri- and post-onset of muscular degeneration to explore the effects in the oxidative muscle soleus and the glycolytic muscle extensor digitorum longus (EDL). We found no overall beneficial effect in the peri-onset group at the conclusion of the study. In the post-onset group, the functional improvement by means of electrophysiological examinations ex vivo was mostly confined to the soleus. EDL benefitted from the treatment on a molecular level but did not improve functionally. Histopathology revealed signs of inflammation at the end of treatment. In conclusion, the growth factor cocktail failed to improve the mdx on a functional level.

This work was supported by grants from the Lundbeck Foundation (Grant No. R140-2013-13370 to J.V. and T.O.K.), Novo Nordisk Foundation (Grant No. 8091 to J.V. and T.O.K.), AP Møller Foundations (Grant No. 13-222 to T.O.K.), Instituto de Salud Carlos III y Fondos FEDER (FIS Project PI19/01313 to T.P.), and Augustinus Foundation (Grant No. 13-4153 to T.O.K.). None of the funding sources had any involvement in the study, data evaluation, or authoring of the manuscript.