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

PDF - Published Version Available under License Creative Commons Attribution. Download (8MB)

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

Citation Data

Cited 6 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item