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Interferon-gamma modulates articular chondrocyte and osteoblast metabolism through protein kinase R-independent and dependent mechanisms

Gilbert, S. J., Blain, E. J. ORCID: https://orcid.org/0000-0001-8944-4254 and Mason, D. J. ORCID: https://orcid.org/0000-0002-8666-6094 2022. Interferon-gamma modulates articular chondrocyte and osteoblast metabolism through protein kinase R-independent and dependent mechanisms. Biochemistry and Biophysics Reports 32 , 101323. 10.1016/j.bbrep.2022.101323

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Abstract

Osteoarthritis (OA) affects multiple tissues of the synovial joint and is characterised by articular cartilage degeneration and bone remodelling. Interferon-γ (IFN-γ) is implicated in osteoarthritis pathology exerting its biological effects via various mechanisms including activation of protein kinase R (PKR), which has been implicated in inflammation and arthritis. This study investigated whether treatment of articular cartilage chondrocytes and osteoblasts with IFN-γ could induce a degradative phenotype that was mediated through the PKR signalling pathway. IFN-γ treatment of chondrocytes increased transcription of key inflammatory mediators (TNF-α, IL-6), matrix degrading enzymes (MMP-13), the transcription factor STAT1, and PKR. Activation of PKR was involved in the regulation of TNF-α, IL-6, and STAT1. In osteoblasts, IFN-γ increased human and mouse STAT1, and human IL-6 through a mechanism involving PKR. ALP, COL1A1 (human and mouse), RUNX2 (mouse), and PHOSPHO1 (mouse) were decreased by IFN-γ. The number of PKR positive cells were increased in post-traumatic OA (PTOA). This study has revealed that IFN-γ propagates inflammatory and degenerative events in articular chondrocytes and osteoblasts via PKR activation. Since IFN-γ and PKR signalling are both activated in early PTOA, these mechanisms are likely to contribute to joint degeneration after injury and might offer attractive targets for therapeutic intervention.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
ISSN: 2405-5808
Funders: Versus Arthritis
Date of First Compliant Deposit: 28 September 2022
Date of Acceptance: 1 August 2022
Last Modified: 05 May 2023 11:30
URI: https://orca.cardiff.ac.uk/id/eprint/152409

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