Inhibition of Myostatin Reduces Collagen Deposition in a Mouse Model of Oculopharyngeal Muscular Dystrophy (OPMD) With Established Disease

Abstract

Background: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disease presented by ptosis, dysphagia, and limb weakness. Affected muscles display increased fibrosis and atrophy, with characteristic inclusion bodies in the nucleus. Myostatin is a negative regulator of muscle mass, and inhibition of myostatin has been demonstrated to improve symptoms in models of muscular dystrophy. Methods: We systemically administered a monoclonal antibody to block myostatin in the A17 mouse model of OPMD at 42 weeks of age. The mice were administered a weekly dose of 10 mg/kg RK35 intraperitonially for 10 weeks, following which serum and histological analyses were performed on muscle samples. Results: The administration of the antibody resulted in a significant decrease in serum myostatin and collagen deposition in muscles. However, minimal effects on body mass, muscle mass and myofiber diameter, or the density of intranuclear inclusions (INIs) (a hallmark of disease progression of OPMD) were observed. Conclusion: This study demonstrates that inhibition of myostatin does not revert muscle atrophy in a mouse model with established OPMD disease, but is effective at reducing observed histological markers of fibrosis in the treated muscles.

Highly Sensitive and Multiplexed Protein Imaging With Cleavable Fluorescent Tyramide Reveals Human Neuronal Heterogeneity

“…Comparison of the two sets of results yields an R 2 value of 0.99 with a slope of 1.13 ( Figure 5B ). All the antibodies we used here are well-validated and widely applied in the previous studies (Maugeri et al, 2014 ; Pellegrini et al, 2018 ; Chen et al, 2019 ; Jia et al, 2019 ; Dubois et al, 2020 ; Harish et al, 2020 ; Li et al, 2020 ; Lin et al, 2020 ; Watson et al, 2020 ; Zhao et al, 2020 ). The staining patterns we obtained are also consistent with the ones generated by antibodies from different clones (Uhlén et al, 2015 ; Thul et al, 2017 ).…”

Multiplexed In Situ Protein Profiling with High-Performance Cleavable Fluorescent Tyramide

“…To evaluate whether PTA and TCEP can cleave the fluorophore and deactivate HRP simultaneously, we stained HMGB1, HDAC2, TAP43, PABPN1, hnRNP A1, Nucleolin, H4K16ac, hnRNP K, ILF3 and Nucleophosmin with HRP labeled antibodies and the high-performance tyramide-N 3 -Cy5 in HeLa cells ( Figure 4 ). All the antibodies used in this study are well-validated and documented in the literature [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. With the PTA and TCEP treatment, over 95% of the staining signals were erased, leading to the on/off ratio of about 20:1.…”

Myokine myostatin is a novel predictor of one-year radiographic progression in patients with rheumatoid arthritis: A prospective cohort study

“…It has been long known that myostatin acts as myokine, negatively regulates skeletal muscle in humans and animal models. An upregulation of myostatin has been shown in several disease models including cancer cachexia, chemotherapy, kidney failure, heart failure, spinal muscular atrophy, vitamin D deficiency in infantile nephropathic cystinosis, and oculopharyngeal muscular dystrophy ( 20 – 22 ). Previous clinical studies involving the relationship between serum myostatin and muscle mass and function are limited.…”