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Author Notes:

Correspondence to: P.P. Nghiem; e-mail: pnghiem@cvm.tamu.edu

The authors thank Dr. Alyson Fiorillo and Dr. Chris Heier for their discussions; Dr. Sree Rayavarapu, Dr. Kanneyboyina Nagaraju, and Dr. Zuyi Wang for their technical assistance; Dr. Larry Fisher for contributing human recombinant osteopontin proteins; and Dan and Janet Bogan and Jennifer Dow for animal care and data collection.

This work was presented in part at the 2012 FASEB Osteopontin Biology Meeting in Saxtons River, Vermont.


Research Funding:

This study was supported by grants from the National Research Service (F32 Grant 1F32AR060703‐01 to P.P.N.), the National Institutes of Health (R01NS029525 to E.P.H.), and the Muscular Dystrophy Association (to E.P.H.).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Clinical Neurology
  • Neurosciences
  • Neurosciences & Neurology
  • AKT
  • dog
  • Duchenne
  • GRMD
  • mdx
  • muscle
  • myostatin
  • osteopontin
  • MICE
  • DOGS

Osteopontin is linked with AKT, FoxO1, and myostatin in skeletal muscle cells

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Journal Title:

Muscle and Nerve


Volume 56, Number 6


, Pages 1119-1127

Type of Work:

Article | Final Publisher PDF


Introduction: Osteopontin (OPN) polymorphisms are associated with muscle size and modify disease progression in Duchenne muscular dystrophy (DMD). We hypothesized that OPN may share a molecular network with myostatin (MSTN). Methods: Studies were conducted in the golden retriever (GRMD) and mdx mouse models of DMD. Follow-up in-vitro studies were employed in myogenic cells and the mdx mouse treated with recombinant mouse (rm) or human (Hu) OPN protein. Results: OPN was increased and MSTN was decreased and levels correlated inversely in GRMD hypertrophied muscle. RM-OPN treatment led to induced AKT1 and FoxO1 phosphorylation, microRNA-486 modulation, and decreased MSTN. An AKT1 inhibitor blocked these effects, whereas an RGD-mutant OPN protein and an RGDS blocking peptide showed similar effects to the AKT inhibitor. RMOPN induced myotube hypertrophy and minimal Feret diameter in mdx muscle. Discussion: OPN may interact with AKT1/MSTN/FoxO1 to modify normal and dystrophic muscle. Muscle Nerve 56: 1119–1127, 2017.

Copyright information:

© 2017 The Authors. Muscle & Nerve Published by Wiley Periodicals, Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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