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‐1β, tumor necrosis factor‐α (TNF‐α), 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 α1 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.

中文翻译：

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NEAT1 / miR‐193a‐3p / SOX5轴可调节人骨关节炎中的软骨基质降解

据报道，长的非编码RNA（lncRNA）参与了骨关节炎（OA）的发展。这项工作的目的是探讨lncRNA核富集丰富转录本1（NEAT1）在OA中的功能。逆转录定量聚合酶链反应（RT-qPCR）用于分析microRNA（miR-193a）-3p，NEAT1和性别决定区域Y-box蛋白5（SOX5）的表达，以及OA软骨组织和软骨细胞中的促炎细胞因子白介素-6（IL-6），IL-1β，肿瘤坏死因子-α（TNF-α）和IL-8。另外，流式细胞术用于测量软骨细胞的凋亡。细胞外基质ACAN，II型胶原α1链（Col2a1），基质金属蛋白酶-3（MMP-3），MMP-13，解整合素，使用Western blot分析确定具有血小板反应蛋白基序（ADAMTS）-5和SOX5的金属蛋白酶。进行双荧光素酶报告基因测定，以确定NEAT1，miR-193a-3p和SOX5之间的靶标关系。我们发现，OA软骨组织和软骨细胞中的miR‐193a‐3p表达下调，而NEAT1和SOX5上调。miR-193a-3p的上调和NEAT1的抑制均抑制炎症，细胞凋亡，并降低MMP-3，MMP-13和ADAMTS-5的蛋白质​​水平，同时提高软骨细胞中ACAN和Col2a1的表达。NEAT1靶向miR‐193a‐3p，而SOX5靶向miR‐193a‐3p。沉默miR‐193a‐3p可逆转NEAT1敲低介导的对炎症，细胞凋亡和细胞外基质产生的作用。SOX5的引入消除了miR-193a-3p上调对软骨细胞炎症，凋亡和细胞外基质产生的影响。总之，NEAT1 / miR-193a-3p / SOX5轴可调节人OA中的软骨基质降解。