Selective Myostatin Inhibition Spares Sublesional Muscle Mass and Myopenia-Related Dysfunction after Severe Spinal Cord Contusion in Mice
Autor: | Gregory E. Bigford, Adriana Donovan, Mark S. Nash, W. Dalton Dietrich, Micah T. Webster |
---|---|
Rok vydání: | 2021 |
Předmět: |
medicine.medical_specialty
medicine.medical_treatment Myostatin Mice Atrophy Internal medicine medicine Animals Myocyte Muscle Skeletal Spinal cord injury Spinal Cord Injuries Soleus muscle biology business.industry Growth factor medicine.disease Mice Inbred C57BL Disease Models Animal Muscular Atrophy Endocrinology Body Composition biology.protein Lean body mass Female Neurology (clinical) business Transforming growth factor |
Zdroj: | Journal of Neurotrauma. 38:3440-3455 |
ISSN: | 1557-9042 0897-7151 |
Popis: | Clinically relevant myopenia accompanies spinal cord injury (SCI), and compromises function, metabolism, body composition, and health. Myostatin, a transforming growth factor (TGF)β family member, is a key negative regulator of skeletal muscle mass. We investigated inhibition of myostatin signaling using systemic delivery of a highly selective monoclonal antibody - muSRK-015P (40 mg/kg) - that blocks release of active growth factor from the latent form of myostatin. Adult female mice (C57BL/6) were subjected to a severe SCI (65 kdyn) at T9 and were then immediately and 1 week later administered test articles: muSRK-015P (40 mg/kg) or control (vehicle or IgG). A sham control group (laminectomy only) was included. At euthanasia, (2 weeks post-SCI) muSRK-015P preserved whole body lean mass and sublesional gastrocnemius and soleus mass. muSRK-015P-treated mice with SCI also had significantly attenuated myofiber atrophy, lipid infiltration, and loss of slow-oxidative phenotype in soleus muscle. These outcomes were accompanied by significantly improved sublesional motor function and muscle force production at 1 and 2 weeks post-SCI. At 2 weeks post-SCI, lean mass was significantly decreased in SCI-IgG mice, but was not different in SCI-muSRK-015P mice than in sham controls. Total energy expenditure (kCal/day) at 2 weeks post-SCI was lower in SCI-immunoglobulin (Ig)G mice, but not different in SCI-muSRK-015P mice than in sham controls. We conclude that in a randomized, blinded, and controlled study in mice, myostatin inhibition using muSRK-015P had broad effects on physical, metabolic, and functional outcomes when compared with IgG control treated SCI animals. These findings may identify a useful, targeted therapeutic strategy for treating post-SCI myopenia and related sequelae in humans. |
Databáze: | OpenAIRE |
Externí odkaz: |