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The lncRNA PILA promotes NF-κB signaling in osteoarthritis by stimulating the activity of the protein arginine methyltransferase PRMT1

Citation

Tang, S and Cao, Y and Cai, Z and Nie, X and Ruan, J and Zhou, Z and Ruan, G and Zhu, Z and Han, W and Ding, C, The lncRNA PILA promotes NF-κB signaling in osteoarthritis by stimulating the activity of the protein arginine methyltransferase PRMT1, Science Signaling, 15, (735) pp. eabm6265. ISSN 1937-9145 (2022) [Refereed Article]


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DOI: doi:10.1126/scisignal.abm6265

Abstract

Inflammatory cytokine–induced activation of nuclear factor κB (NF-κB) signaling plays a critical role in the pathogenesis of osteoarthritis (OA). We identified PILA as a long noncoding RNA (lncRNA) that enhances NF-κB signaling and OA. The abundance of PILA was increased in damaged cartilage from patients with OA and in human articular chondrocytes stimulated with the proinflammatory cytokine tumor necrosis factor (TNF). Knockdown of PILA inhibited TNF-induced NF-κB signaling, extracellular matrix catabolism, and apoptosis in chondrocytes, whereas ectopic expression of PILA promoted NF-κB signaling and matrix degradation. PILA promoted PRMT1-mediated arginine methylation of DExH-box helicase 9 (DHX9), leading to an increase in the transcription of the gene encoding transforming growth factor β–activated kinase 1 (TAK1), an upstream activator of NF-κB signaling. Furthermore, intra-articular injection of an adenovirus vector encoding PILA triggered spontaneous cartilage loss and exacerbated posttraumatic OA in mice. This study provides insight into the regulation of NF-κB signaling in OA and identifies a potential therapeutic target for this disease.

Item Details

Item Type:Refereed Article
Keywords:cytokines, interleukin-1beta, NF-kappa B, long noncoding RNA, repressor, proteins, PRMT1 protein, human, Arginine N-Methyltransferases
Research Division:Biomedical and Clinical Sciences
Research Group:Medical biochemistry and metabolomics
Research Field:Medical biochemistry - nucleic acids
Objective Division:Health
Objective Group:Clinical health
Objective Field:Prevention of human diseases and conditions
UTAS Author:Ding, C (Professor Chang-Hai Ding)
ID Code:150219
Year Published:2022
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-06-02
Last Modified:2022-06-06
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