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

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 and Yousef Abu-Amer ()
Additional contact information
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
Takashi Maruyama: Akita University School of Medicine
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

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-17242-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17242-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-17242-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().