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NEAT1/miR‐193a‐3p/SOX5 axis regulates cartilage matrix degradation in human osteoarthritis
Author(s) -
Liu Feng,
Liu Xiangyang,
Yang Yue,
Sun Zhibo,
Deng Shuang,
Jiang Zhongping,
Li Wen,
Wu Fei
Publication year - 2020
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11291
Subject(s) - gene knockdown , chemistry , downregulation and upregulation , adamts , cartilage , matrix metalloproteinase , microbiology and biotechnology , chondrocyte , extracellular matrix , thrombospondin , gene silencing , apoptosis , cancer research , biology , metalloproteinase , biochemistry , gene , anatomy
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.