Background: Duchenne muscular dystrophy (DMD) is an inherited lethal muscle wasting disease characterized by cycles of degeneration and regeneration, with no effective therapy. Growth differentiation factor 11 (GDF11), a member of the TGF-β superfamily and myostatin homologous, has been reported to have the capacity to reverse age-related skeletal muscle loss. These initial findings led us to investigate the ability of GDF11 to promote regeneration in the context of muscular dystrophy and determine whether it could be a candidate to slow down or reverse the disease progression in DMD. Results: Here, we delivered recombinant GDF11 (rGDF11) to dystrophin-deficient mice using the intra-peritoneal route for 30 days and evaluated histology and function in both steady-state and cardiotoxin-injured muscles. Our data confirmed that treatment with rGDF11 resulted in elevated levels of this factor in the circulation. However, this had no effect on muscle contractility nor on muscle histology. Moreover, no difference was found in the number of regenerating myofibers displaying centrally located nuclei. On the other hand, we did observe increased collagen content, which denotes fibrosis, in the muscles of rGDF11-treated dystrophic mice. Conclusions: Taken together, our findings indicate no beneficial effect of treating dystrophic mice with rGDF11 and raise caution to a potential harmful effect, as shown by the pro-fibrotic outcome.
Bibliographical noteFunding Information:
We thank the JB’s Key’s Fund for their generous support for this project. The project was also supported by NIH grant AR055299 (RCRP), the Muscular Dystrophy Center Core Laboratories P30-AR0507220, as well as funding from the MDA (#238127 to RCRP). Y.Z. and R.M-G. were funded by fellowships from the Oversea Study Program of Guangzhou Elite Project-China and CONACyT-Mexico (#394378), respectively.
© 2016 Rinaldi et al.
- Duchenne muscular dystrophy
- Muscle regeneration