Glutamine metabolism modulates chondrocyte inflammatory response
- Washington University Medical Center, United States
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file. Source data have been provided for all figures
Article and author information
Author details
Muhammad Farooq Rai
Gabriel Mbalaviele
Funding
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR072623)
- Yousef Abu-Amer
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR074992)
- Yousef Abu-Amer
Shriners Hospitals for Children (85160-STL-20)
- Yousef Abu-Amer
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR076758)
- Gabriel Mbalaviele
National Institutes of Health (AI161022)
- Gabriel Mbalaviele
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#21-0413) of Washington University. All surgery was performed under sodium pentobarbital anesthesia, and every effort was made to minimize suffering.
Reviewing Editor
- Jameel Iqbal, DaVita Labs, United States
Version history
- Received: June 1, 2022
- Preprint posted: June 9, 2022 (view preprint)
- Accepted: August 1, 2022
- Accepted Manuscript published: August 2, 2022 (version 1)
- Version of Record published: August 11, 2022 (version 2)
Copyright
© 2022, Arra et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Glutamine metabolism modulates chondrocyte inflammatory response
eLife 11:e80725.
https://doi.org/10.7554/eLife.80725
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