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

• Type of Material: Article
• Authors: Peter P. Nghiem, Texas A&M University; Joe Kornegay, Emory University; Kitipong Uaesoontrachoon, AGADA Biosciences, Inc; Luca Bello, University of Padova; Ying Yin, National Institutes of Health; Akancha Kesari, Emory University; Priya Mittal, St. Jude Children's Research Hospital; Scott J. Schatzberg, The Animal Neurology & Imaging Center; Gina M. Many, Central Washington University; Norman H. Lee, The George Washington University; Eric P. Hoffman, State University of New York, Binghamton
• Language: English
• Date: 2017-12-01
• Publisher: Wiley: 12 months
• Publication Version: Final Published Version
• Copyright Statement: © 2017 The Authors. Muscle & Nerve Published by Wiley Periodicals, Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/mus.25752
• Title of Journal or Parent Work: Muscle and Nerve
• ISSN: 0148-639X
• Volume: 56
• Issue: 6
• Start Page: 1119
• End Page: 1127
• Grant/Funding Information: 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.).
• Keywords: PATHWAY; EXPRESSION; muscle; Neurosciences & Neurology; REGENERATION; Life Sciences & Biomedicine; Duchenne; ACTIVATION; dog; mdx; myostatin; MICE; TRANSCRIPTION FACTOR; AKT; GRMD; TGF-BETA; Clinical Neurology; Science & Technology; Neurosciences; RETRIEVER MUSCULAR-DYSTROPHY; CRANIAL SARTORIUS MUSCLE; DOGS; osteopontin
• Research Categories: Engineering, Biomedical; Health Sciences, Oncology; Biology, Genetics

Abstract

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.