Myostatin induces tumor necrosis factor-α expression in rheumatoid arthritis synovial fibroblasts through the PI3K-Akt signaling pathway.

Abstract

In rheumatoid arthritis (RA), a chronic inflammatory disease, loss of muscle mass is an important contributor to the loss of muscle strength in RA patients. Myostatin, a myokine involved in the process of muscle hypertrophy and myogenesis, enhances osteoclast differentiation and inflammation. Here, we investigated the mechanisms of myostatin in RA synovial inflammation. We found a positive correlation between myostatin and tumor necrosis factor-α (TNF-α), a well-known proinflammatory cytokine, in RA synovial tissue. Our in vitro results also showed that myostatin dose-dependently induced TNF-α expression through the phosphatidylinositol 3-kinase (PI3K)-Akt-AP-1 signaling pathway. Myostatin treatment of human MH7A cells stimulated AP-1-induced luciferase activity and activation of the c-Jun binding site on the TNF-α promoter. Our results indicated that myostatin increases TNF-α expression via the PI3K-Akt-AP-1 signaling pathway in human RA synovial fibroblasts. Myostatin appears to be a promising target in RA therapy.

• Authors: Chen-Ming Su, Sung-Lin Hu, Yi Sun, Jin Zhao, Chengqian Dai, Lihong Wang, Guohong Xu, Chih-Hsin Tang
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 6 Pg. 9793-9801 (06 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 30378113 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Myostatin
• Transcription Factor AP-1
• Tumor Necrosis Factor-alpha
• Proto-Oncogene Proteins c-akt

Topics

• Arthritis, Rheumatoid (metabolism)
• Cell Line
• Fibroblasts (metabolism)
• Gene Expression Regulation (drug effects)
• Humans
• Myostatin (pharmacology)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Signal Transduction
• Synovial Membrane (drug effects, metabolism)
• Transcription Factor AP-1 (genetics, metabolism)
• Tumor Necrosis Factor-alpha (genetics, metabolism)