1. Oncostatin M signaling drives cancer-associated skeletal muscle wasting.
- Author
-
Domaniku-Waraich A, Agca S, Toledo B, Sucuoglu M, Özen SD, Bilgic SN, Arabaci DH, Kashgari AE, and Kir S
- Subjects
- Animals, Humans, Mice, Muscle Fibers, Skeletal metabolism, Muscular Atrophy metabolism, Muscular Atrophy pathology, Neoplasms pathology, Oncostatin M genetics, Oncostatin M metabolism, Oncostatin M pharmacology, Quality of Life
- Abstract
Progressive weakness and muscle loss are associated with multiple chronic conditions, including muscular dystrophy and cancer. Cancer-associated cachexia, characterized by dramatic weight loss and fatigue, leads to reduced quality of life and poor survival. Inflammatory cytokines have been implicated in muscle atrophy; however, available anticytokine therapies failed to prevent muscle wasting in cancer patients. Here, we show that oncostatin M (OSM) is a potent inducer of muscle atrophy. OSM triggers cellular atrophy in primary myotubes using the JAK/STAT3 pathway. Identification of OSM targets by RNA sequencing reveals the induction of various muscle atrophy-related genes, including Atrogin1. OSM overexpression in mice causes muscle wasting, whereas muscle-specific deletion of the OSM receptor (OSMR) and the neutralization of circulating OSM preserves muscle mass and function in tumor-bearing mice. Our results indicate that activated OSM/OSMR signaling drives muscle atrophy, and the therapeutic targeting of this pathway may be useful in preventing muscle wasting., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF