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

Autor:	Gilbert SJ; Biomechanics & Bioengineering Centre Versus Arthritis, School of Biosciences, Cardiff University, CF10 3AX, UK., Blain EJ; Biomechanics & Bioengineering Centre Versus Arthritis, School of Biosciences, Cardiff University, CF10 3AX, UK., Mason DJ; Biomechanics & Bioengineering Centre Versus Arthritis, School of Biosciences, Cardiff University, CF10 3AX, UK.
Jazyk:	angličtina
Zdroj:	Biochemistry and biophysics reports [Biochem Biophys Rep] 2022 Sep 07; Vol. 32, pp. 101323. Date of Electronic Publication: 2022 Sep 07 (Print Publication: 2022).
DOI:	10.1016/j.bbrep.2022.101323
Abstrakt:	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. (© 2022 The Authors. Published by Elsevier B.V.)
Databáze:	MEDLINE
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