NEAT1/miR-193a-3p/SOX5 axis regulates cartilage matrix degradation in human osteoarthritis

Long non-coding RNAs (lncRNAs) were reported to be involved in the progression of osteoarthritis (OA). The aim of this work was to explore the functional role of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in OA. Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was employed to analyze the expression of microRNA (miR-193a)-3p, NEAT1, and sex-determining region Y-box protein 5 (SOX5), as well as the levels of pro-inflammatory cytokines interleukin-6 (IL-6), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), and IL-8 in OA cartilage tissue and chondrocytes. In addition, flow cytometry was used to measure the apoptosis of chondrocytes. The protein levels of extracellular matrix ACAN, collagen type II alpha 1 chain (Col2a1), matrix metalloproteinase-3 (MMP-3), MMP-13, a disintegrin, and metalloproteinase with thrombospondin motifs (ADAMTS)-5 and SOX5 were determined using western blot analysis. Dual-luciferase reporter assay was performed to determine the target relationship among NEAT1, miR-193a-3p, and SOX5. We found that miR-193a-3p expression was downregulated, while NEAT1 and SOX5 were upregulated in OA cartilage tissue and chondrocytes. Both upregulation of miR-193a-3p and knockdown of NEAT1 suppressed inflammation, apoptosis, and reduced the protein levels of MMP-3, MMP-13, and ADAMTS-5, while elevating ACAN and Col2a1 expression in chondrocytes. NEAT1 targeted miR-193a-3p, and SOX5 was targeted by miR-193a-3p. Silencing of miR-193a-3p reversed the NEAT1 knockdown-mediated effect on the inflammation, apoptosis, and production of the extracellular matrix. The introduction of SOX5 abolished the impact of the upregulation of miR-193a-3p on inflammation, apoptosis, and production of extracellular matrix in chondrocytes. In conclusion, NEAT1/miR-193a-3p/SOX5 axis regulates cartilage matrix degradation in human OA.