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

  1. Manoj Arra

    Department of Orthopaedic Surgery, Washington University Medical Center, St Louis, United States
    Competing interests
    No competing interests declared.
  2. Gaurav Swarnkar

    Department of Orthopaedic Surgery, Washington University Medical Center, St Louis, United States
    Competing interests
    No competing interests declared.
  3. Naga Suresh Adapala

    Department of Orthopaedic Surgery, Washington University Medical Center, St Louis, United States
    Competing interests
    No competing interests declared.
  4. Syeda-Kanwal Batool Naqvi

    Department of Orthopaedic Surgery, Washington University Medical Center, St Louis, United States
    Competing interests
    No competing interests declared.
  5. Lei Cai

    Department of Orthopaedic Surgery, Washington University Medical Center, St Louis, United States
    Competing interests
    No competing interests declared.
  6. Muhammad Farooq Rai

    Department of Orthopaedic Surgery, Washington University Medical Center, St Louis, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4826-4331
  7. Srikanth Singamaneni

    Department of Mechanical Engineering and Material Sciences, Washington University Medical Center, St Louis, United States
    Competing interests
    No competing interests declared.
  8. Gabriel Mbalaviele

    Bone and Mineral Division, Washington University Medical Center, St Louis, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4660-0952
  9. Robert Brophy

    Department of Orthopaedic Surgery, Washington University Medical Center, Saint Louis, United States
    Competing interests
    No competing interests declared.
  10. Yousef Abu-Amer

    Department of Orthopaedic Surgery, Washington University Medical Center, St Louis, United States
    For correspondence
    abuamery@wustl.edu
    Competing interests
    Yousef Abu-Amer, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5890-5086

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.

Reviewing Editor

  1. Jameel Iqbal, DaVita Labs, United States

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.

Version history

  1. Received: June 1, 2022
  2. Preprint posted: June 9, 2022 (view preprint)
  3. Accepted: August 1, 2022
  4. Accepted Manuscript published: August 2, 2022 (version 1)
  5. 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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  1. Manoj Arra
  2. Gaurav Swarnkar
  3. Naga Suresh Adapala
  4. Syeda-Kanwal Batool Naqvi
  5. Lei Cai
  6. Muhammad Farooq Rai
  7. Srikanth Singamaneni
  8. Gabriel Mbalaviele
  9. Robert Brophy
  10. Yousef Abu-Amer
(2022)
Glutamine metabolism modulates chondrocyte inflammatory response
eLife 11:e80725.
https://doi.org/10.7554/eLife.80725

Share this article

https://doi.org/10.7554/eLife.80725

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