IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-17242-0.html
   My bibliography  Save this article

LDHA-mediated ROS generation in chondrocytes is a potential therapeutic target for osteoarthritis

Author

Listed:
  • Manoj Arra

    (Washington University School of Medicine)

  • Gaurav Swarnkar

    (Washington University School of Medicine)

  • Ke Ke

    (Washington University School of Medicine)

  • Jesse E. Otero

    (OrthoCarolina Hip and Knee Center)

  • Jun Ying

    (Washington University School of Medicine)

  • Xin Duan
  • Takashi Maruyama

    (Akita University School of Medicine
    National Institutes of Health)

  • Muhammad Farooq Rai

    (Washington University School of Medicine)

  • Regis J. O’Keefe

    (Washington University School of Medicine)

  • Gabriel Mbalaviele

    (Bone and Mineral Division, Department of Medicine, Washington University School of Medicine)

  • Jie Shen

    (Washington University School of Medicine)

  • Yousef Abu-Amer

    (Washington University School of Medicine
    Shriners Hospital for Children)

Abstract

The contribution of inflammation to the chronic joint disease osteoarthritis (OA) is unclear, and this lack of clarity is detrimental to efforts to identify therapeutic targets. Here we show that chondrocytes under inflammatory conditions undergo a metabolic shift that is regulated by NF-κB activation, leading to reprogramming of cell metabolism towards glycolysis and lactate dehydrogenase A (LDHA). Inflammation and metabolism can reciprocally modulate each other to regulate cartilage degradation. LDHA binds to NADH and promotes reactive oxygen species (ROS) to induce catabolic changes through stabilization of IκB-ζ, a critical pro-inflammatory mediator in chondrocytes. IκB-ζ is regulated bi-modally at the stages of transcription and protein degradation. Overall, this work highlights the function of NF-κB activity in the OA joint as well as a ROS promoting function for LDHA and identifies LDHA as a potential therapeutic target for OA treatment.

Suggested Citation

  • Manoj Arra & Gaurav Swarnkar & Ke Ke & Jesse E. Otero & Jun Ying & Xin Duan & Takashi Maruyama & Muhammad Farooq Rai & Regis J. O’Keefe & Gabriel Mbalaviele & Jie Shen & Yousef Abu-Amer, 2020. "LDHA-mediated ROS generation in chondrocytes is a potential therapeutic target for osteoarthritis," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17242-0
    DOI: 10.1038/s41467-020-17242-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-17242-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-17242-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Kosei Nagata & Hironori Hojo & Song Ho Chang & Hiroyuki Okada & Fumiko Yano & Ryota Chijimatsu & Yasunori Omata & Daisuke Mori & Yuma Makii & Manabu Kawata & Taizo Kaneko & Yasuhide Iwanaga & Hideki N, 2022. "Runx2 and Runx3 differentially regulate articular chondrocytes during surgically induced osteoarthritis development," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Zhe Gong & Jinjin Zhu & Junxin Chen & Fan Feng & Haitao Zhang & Zheyuan Zhang & Chenxin Song & Kaiyu Liang & Shuhui Yang & Shunwu Fan & Xiangqian Fang & Shuying Shen, 2023. "CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    3. Kun Zhang & Pengfei Wang & Wei Huang & Shi-Hao Tang & Hanzhong Xue & Hao Wu & Ying Zhang & Yu Rong & Shan-Shan Dong & Jia-Bin Chen & Yan Zou & Ding Tian & Na Yang & Yifan Liang & Chungui Liu & Dongyan, 2024. "Integrated landscape of plasma metabolism and proteome of patients with post-traumatic deep vein thrombosis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17242-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.