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

Document Type

Journal Article

Publication Date

12-1-2017

Journal

Muscle and Nerve

Volume

56

Issue

6

DOI

10.1002/mus.25752

Keywords

AKT; dog; Duchenne; GRMD; mdx; muscle; myostatin; osteopontin

Abstract

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

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