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The effects of two TGF‐beta superfamily ligand trapping agents on the morphology of dystrophic (mdx) Triangularis Sterni (TS) muscle
Author(s) -
Nielsen Cory,
Borowy Christopher,
Jacinto Kimberly,
Potter Ross,
Kaminski Carter,
Kumar Ravi,
Carlson C George
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1038.5
Subject(s) - myostatin , duchenne muscular dystrophy , myogenesis , receptor , chemistry , skeletal muscle , microbiology and biotechnology , mdx mouse , medicine , biology , endocrinology , anatomy , dystrophin , biochemistry
The severely dystrophic mdx TS muscle provides a useful template for examining the translational efficacy of various signaling modulators in ameliorating dystrophic pathology. Two critical skeletal muscle modulators are myostatin and TGFβ, which activate the same smad signaling pathway through their respective receptors, ActRIIB and TGFβRII. To independently examine the relative effects of myostatin and TGFβ signaling on dystrophic fiber morphology, we administered either an ActRIIB (RAP‐031, RAP‐435) or a TGFβRII ligand trapping agent (TGFβRII‐F c ) in vivo to mdx mice for 1 month or 3 month periods. There was an increase in fiber and myonuclei density following 1 month treatment with RAP‐031, RAP‐435, or TGFβRII‐F c. After 3 months treatment with RAP‐435, there was a significant increase in fiber and myonuclei density across all regions of the TS but no effect on Feret's minimal diameter. In addition, 3 month RAP‐435 treated preparations showed a decrease in central nucleation. Histograms of the number of fibers with centrally located nuclei followed a Poisson distribution. This indicates that the probability of a nucleus occupying a central location does not depend upon the presence of other centrally located nuclei and is identical for each myonucleus within a given fiber. Experiments examining the effects of a 3 month treatment with TGFβRII‐F c are underway. These results indicate that ActRIIB inhibition promotes satellite cell regeneration and fusion into new myotubes and does not increase individual fiber growth in the mdx TS.