title: A Soluble Activin Receptor IIB Fails to Prevent Muscle Atrophy in a Mouse Model of Spinal Cord Injury.
abstract: Myostatin (MST) is a potent regulator of muscle growth and size. Spinal cord injury (SCI) results in marked atrophy of muscle below the level of injury. Currently, there is no effective pharmaceutical treatment available to prevent sublesional muscle atrophy post-SCI. To determine whether inhibition of MST with a soluble activin IIB receptor (RAP-031) prevents sublesional SCI-induced muscle atrophy, mice were randomly assigned to the following groups: Sham-SCI; SCI+Vehicle group (SCI-VEH); and SCI+RAP-031 (SCI-RAP-031). SCI was induced by complete transection at thoracic level 10. Animals were euthanized at 56 days post-surgery. RAP-031 reduced, but did not prevent, body weight loss post-SCI. RAP-031 increased total lean tissue mass compared to SCI-VEH (14.8%). RAP-031 increased forelimb muscle mass post-SCI by 38% and 19% for biceps and triceps, respectively (p < 0.001). There were no differences in hindlimb muscle weights between the RAP-031 and SCI-VEH groups. In the gastrocnemius, messenger RNA (mRNA) expression was elevated for interleukin (IL)-6 (8-fold), IL-1β (3-fold), and tumor necrosis factor alpha (8-fold) in the SCI-VEH, compared to the Sham group. Muscle RING finger protein 1 mRNA was 2-fold greater in the RAP-031 group, compared to Sham-SCI. RAP-031 did not influence cytokine expression. Bone mineral density of the distal femur and proximal tibia were decreased post-SCI (-26% and -28%, respectively) and were not altered by RAP-031. In conclusion, MST inhibition increased supralesional muscle mass, but did not prevent sublesional muscle or bone loss, or the inflammation in paralyzed muscle.
authors.affiliation: 1 National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center , Bronx, New York.|5 Department of Medicine, Icahn School of Medicine at Mount Sinai , New York, New York.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Graham
authors.affiliation: 1 National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center , Bronx, New York.
authors.forename: Lauren
authors.initials: L
authors.lastname: Collier
authors.affiliation: 1 National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center , Bronx, New York.
authors.forename: Yuanzhen
authors.initials: Y
authors.lastname: Peng
authors.affiliation: 3 Department of Physiology, Pontificia Universidad Católica , Santiago, Chile .|4 Centro Interdisciplinario de Neurociencias de Valparaiso , Valparaiso, Chile .
authors.forename: Juan C
authors.initials: JC
authors.lastname: Saéz
authors.affiliation: 1 National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center , Bronx, New York.|2 Medical Service, James J. Peters VA Medical Center , Bronx, New York.|5 Department of Medicine, Icahn School of Medicine at Mount Sinai , New York, New York.|6 Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai , New York, New York.
authors.forename: William A
authors.initials: WA
authors.lastname: Bauman
authors.affiliation: 1 National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center , Bronx, New York.|5 Department of Medicine, Icahn School of Medicine at Mount Sinai , New York, New York.
authors.forename: Weiping
authors.initials: W
authors.lastname: Qin
authors.affiliation: 1 National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center , Bronx, New York.|2 Medical Service, James J. Peters VA Medical Center , Bronx, New York.|5 Department of Medicine, Icahn School of Medicine at Mount Sinai , New York, New York.|6 Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai , New York, New York.|7 Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai , New York, New York.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cardozo
mesh_terms: D030301:Activin Receptors, Type II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000209:etiology / Q000517:prevention & control*; D055435:Myostatin / Q000187:drug effects*; D011897:Random Allocation; D013119:Spinal Cord Injuries / Q000150:complications*
chemical_list: C525912:Mstn protein, mouse; D055435:Myostatin; D030301:Activin Receptors, Type II
keywords: inflammation; metabolism; neural injury; spinal cord injury