Metabolic rewiring controlled by c-Fos governs cartilage integrity in osteoarthritis.


Journal

Annals of the rheumatic diseases
ISSN: 1468-2060
Titre abrégé: Ann Rheum Dis
Pays: England
ID NLM: 0372355

Informations de publication

Date de publication:
09 2023
Historique:
received: 09 02 2023
accepted: 11 05 2023
medline: 14 8 2023
pubmed: 22 6 2023
entrez: 21 6 2023
Statut: ppublish

Résumé

The activator protein-1 (AP-1) transcription factor component c-Fos regulates chondrocyte proliferation and differentiation, but its involvement in osteoarthritis (OA) has not been functionally assessed. c-Fos expression was evaluated by immunohistochemistry on articular cartilage sections from patients with OA and mice subjected to the destabilisation of the medial meniscus (DMM) model of OA. Cartilage-specific c-Fos knockout (c-Fos FOS-positive chondrocytes were increased in human and murine OA cartilage during disease progression. Compared with c-Fos c-Fos modulates cellular bioenergetics in chondrocytes by balancing pyruvate flux between anaerobic glycolysis and the tricarboxylic acid cycle in response to OA signals. We identify a novel metabolic adaptation of chondrocytes controlled by c-Fos-containing AP-1 dimers that could be therapeutically relevant.

Identifiants

pubmed: 37344157
pii: ard-2023-224002
doi: 10.1136/ard-2023-224002
pmc: PMC10423482
doi:

Substances chimiques

Collagen 9007-34-5
Transcription Factor AP-1 0
FOS protein, human 0
Fos protein, mouse 0
Proto-Oncogene Proteins c-fos 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1227-1239

Informations de copyright

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

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Auteurs

Kazuhiko Matsuoka (K)

Genes and Disease group, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Cellular and Molecular Tumor biology, Center for Cancer Research, Medical University of Vienna, Vienna, Austria.

Latifa Bakiri (L)

Genes and Disease group, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.

Martin Bilban (M)

Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Core Facilities, Medical University of Vienna, Vienna, Austria.

Stefan Toegel (S)

Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria.
Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Vienna, Austria.

Arvand Haschemi (A)

Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.

Hao Yuan (H)

Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.

Maria Kasper (M)

Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.

Reinhard Windhager (R)

Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria.

Erwin F Wagner (EF)

Genes and Disease group, Department of Dermatology, Medical University of Vienna, Vienna, Austria erwin.wagner@meduniwien.ac.at.
Genes and Disease group, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.

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