Glutamine metabolism modulates chondrocyte inflammatory response

Author:

Arra Manoj1,Swarnkar Gaurav1,Adapala Naga Suresh1,Naqvi Syeda Kanwal1,Cai Lei1,Farooq Rai Muhammad1ORCID,Singamaneni Srikanth2,Mbalaviele Gabriel3ORCID,Brophy Robert1,Abu-Amer Yousef14ORCID

Affiliation:

1. Department of Orthopedic Surgery, Washington University School of Medicine

2. Department of Mechanical Engineering and Material Sciences, Washington University School of Medicine

3. Bone and Mineral Division, Department of Medicine, Washington University School of Medicine

4. Shriners Hospital for Children

Abstract

Osteoarthritis is the most common joint disease in the world with significant societal consequences but lacks effective disease-modifying interventions. The pathophysiology consists of a prominent inflammatory component that can be targeted to prevent cartilage degradation and structural defects. Intracellular metabolism has emerged as a culprit of the inflammatory response in chondrocytes, with both processes co-regulating each other. The role of glutamine metabolism in chondrocytes, especially in the context of inflammation, lacks a thorough understanding and is the focus of this work. We display that mouse chondrocytes utilize glutamine for energy production and anabolic processes. Furthermore, we show that glutamine deprivation itself causes metabolic reprogramming and decreases the inflammatory response of chondrocytes through inhibition of NF-κB activity. Finally, we display that glutamine deprivation promotes autophagy and that ammonia is an inhibitor of autophagy. Overall, we identify a relationship between glutamine metabolism and inflammatory signaling and display the need for increased study of chondrocyte metabolic systems.

Funder

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Shriners Hospitals for Children

National Institutes of Health

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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