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Gene therapy for follistatin mitigates systemic metabolic inflammation and post-traumatic arthritis in high-fat diet-induced obesity

Authors
 Ruhang Tang  ;  Natalia S Harasymowicz  ;  Chia-Lung Wu  ;  Kelsey H Collins  ;  Yun-Rak Choi  ;  Sara J Oswald  ;  Farshid Guilak 
Citation
 SCIENCE ADVANCES, Vol.6(19) : eaaz7492, 2020-05 
Journal Title
 SCIENCE ADVANCES 
Issue Date
2020-05
Abstract
Obesity-associated inflammation and loss of muscle function play critical roles in the development of osteoarthritis (OA); thus, therapies that target muscle tissue may provide novel approaches to restoring metabolic and biomechanical dysfunction associated with obesity. Follistatin (FST), a protein that binds myostatin and activin, may have the potential to enhance muscle formation while inhibiting inflammation. Here, we hypothesized that adeno-associated virus 9 (AAV9) delivery of FST enhances muscle formation and mitigates metabolic inflammation and knee OA caused by a high-fat diet in mice. AAV-mediated FST delivery exhibited decreased obesity-induced inflammatory adipokines and cytokines systemically and in the joint synovial fluid. Regardless of diet, mice receiving FST gene therapy were protected from post-traumatic OA and bone remodeling induced by joint injury. Together, these findings suggest that FST gene therapy may provide a multifactorial therapeutic approach for injury-induced OA and metabolic inflammation in obesity.
Files in This Item:
T202005624.pdf Download
DOI
10.1126/sciadv.aaz7492
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
Yonsei Authors
Choi, Yun Rak(최윤락)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/181398
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