LAUSR

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. Description The lncRNA PILA exacerbates osteoarthritis by enhancing NF-κB–mediated inflammatory signaling. Joint degeneration by lncRNA Nuclear factor κB (NF-κB) signaling contributes to the development and progression of osteoarthritis (OA) by promoting cartilage degradation and joint inflammation. Tang et al. found that the long noncoding RNA PILA stimulated NF-κB signaling in OA. In human articular chondrocytes, PILA interacted with and stimulated the activity of the protein arginine methyltransferase PRMT1. Modification of the RNA helicase DHX9 by PRMT1 increased the expression of TAK1, which encodes a kinase that promotes the activation of NF-κB. PILA was increased in abundance in human osteoarthritic cartilage and enhanced inflammation-induced extracellular matrix degradation in articular chondrocytes. Expression of PILA in the knee joints of mice stimulated spontaneous cartilage degradation and enhanced experimentally induced OA. Together, these findings identify PILA as a factor that promotes articular cartilage degradation and exacerbates inflammation-induced joint damage in OA by augmenting NF-κB signaling.