Spontaneously Resolving Joint Inflammation Is Characterised by Metabolic Agility of Fibroblast-Like Synoviocytes.


Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2021
Historique:
received: 15 06 2021
accepted: 09 08 2021
entrez: 13 9 2021
pubmed: 14 9 2021
medline: 12 1 2022
Statut: epublish

Résumé

Fibroblast-like synoviocytes (FLS) play an important role in maintaining joint homeostasis and orchestrating local inflammatory processes. When activated during injury or inflammation, FLS undergo transiently increased bioenergetic and biosynthetic demand. We aimed to identify metabolic changes which occur early in inflammatory disease pathogenesis which might support sustained cellular activation in persistent inflammation. We took primary human FLS from synovial biopsies of patients with very early rheumatoid arthritis (veRA) or resolving synovitis, and compared them with uninflamed control samples from the synovium of people without arthritis. Metabotypes were compared using NMR spectroscopy-based metabolomics and correlated with serum C-reactive protein levels. We measured glycolysis and oxidative phosphorylation by Seahorse analysis and assessed mitochondrial morphology by immunofluorescence. We demonstrate differences in FLS metabolism measurable after

Identifiants

pubmed: 34512657
doi: 10.3389/fimmu.2021.725641
pmc: PMC8426599
doi:

Substances chimiques

TNF protein, human 0
Tumor Necrosis Factor-alpha 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

725641

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Versus Arthritis
ID : 22072
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : 19791
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : 20298
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S025308/1
Pays : United Kingdom
Organisme : Versus Arthritis
ID : 21802
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : 20015
Pays : United Kingdom

Informations de copyright

Copyright © 2021 Falconer, Pucino, Clayton, Marshall, Raizada, Adams, Philp, Clark, Filer, Raza, Young and Buckley.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Jane Falconer (J)

Rheumatology Research Group, Institute for Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom.
School of Medicine, Institute of Health Sciences and Wellbeing, University of Sunderland, Sunderland, United Kingdom.

Valentina Pucino (V)

Rheumatology Research Group, Institute for Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom.

Sally A Clayton (SA)

Rheumatology Research Group, Institute for Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom.
Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.

Jennifer L Marshall (JL)

Rheumatology Research Group, Institute for Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom.

Sabrina Raizada (S)

Rheumatology Research Group, Institute for Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom.

Holly Adams (H)

Rheumatology Research Group, Institute for Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom.

Andrew Philp (A)

Healthy Ageing Theme, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
St Vincent's Clinical School, UNSW Medicine, UNSW Sydney, Sydney, NSW, Australia.

Andrew R Clark (AR)

Rheumatology Research Group, Institute for Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom.

Andrew Filer (A)

Rheumatology Research Group, Institute for Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom.

Karim Raza (K)

Rheumatology Research Group, Institute for Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom.
Department of Rheumatology, Sandwell and West Birmingham NHS Trust, Birmingham, United Kingdom.

Stephen P Young (SP)

Rheumatology Research Group, Institute for Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom.

Christopher D Buckley (CD)

Rheumatology Research Group, Institute for Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom.
Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.

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