PMID- 31868949 OWN - NLM STAT- MEDLINE DCOM- 20201119 LR - 20201119 IS - 1095-8355 (Electronic) IS - 1065-6995 (Linking) VI - 44 IP - 4 DP - 2020 Apr TI - NEAT1/miR-193a-3p/SOX5 axis regulates cartilage matrix degradation in human osteoarthritis. PG - 947-957 LID - 10.1002/cbin.11291 [doi] AB - 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-1beta, 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 alpha1 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. CI - (c) 2019 International Federation for Cell Biology. FAU - Liu, Feng AU - Liu F AD - Department of Orthopedics, The Renmin Hospital of Wuhan University, No. 238 Jiefang Road, and No. 99 Zhangzhidong Road, Wuchang District, 430061, Wuhan, Hubei, China. FAU - Liu, Xiangyang AU - Liu X AD - Department of Orthopedics, The Renmin Hospital of Wuhan University, No. 238 Jiefang Road, and No. 99 Zhangzhidong Road, Wuchang District, 430061, Wuhan, Hubei, China. FAU - Yang, Yue AU - Yang Y AD - Department of Orthopedics, The Renmin Hospital of Wuhan University, No. 238 Jiefang Road, and No. 99 Zhangzhidong Road, Wuchang District, 430061, Wuhan, Hubei, China. FAU - Sun, Zhibo AU - Sun Z AD - Department of Orthopedics, The Renmin Hospital of Wuhan University, No. 238 Jiefang Road, and No. 99 Zhangzhidong Road, Wuchang District, 430061, Wuhan, Hubei, China. FAU - Deng, Shuang AU - Deng S AD - Department of Orthopedics, The Renmin Hospital of Wuhan University, No. 238 Jiefang Road, and No. 99 Zhangzhidong Road, Wuchang District, 430061, Wuhan, Hubei, China. FAU - Jiang, Zhongping AU - Jiang Z AD - Department of Emergency, The Renmin Hospital of Wuhan University, No. 238 Jiefang Road, and No. 99 Zhangzhidong Road, Wuchang District, 430061, Wuhan, Hubei, China. FAU - Li, Wen AU - Li W AD - Department of Emergency, The Renmin Hospital of Wuhan University, No. 238 Jiefang Road, and No. 99 Zhangzhidong Road, Wuchang District, 430061, Wuhan, Hubei, China. FAU - Wu, Fei AU - Wu F AD - Department of Orthopedics, The Renmin Hospital of Wuhan University, No. 238 Jiefang Road, and No. 99 Zhangzhidong Road, Wuchang District, 430061, Wuhan, Hubei, China. LA - eng PT - Journal Article DEP - 20200107 PL - England TA - Cell Biol Int JT - Cell biology international JID - 9307129 RN - 0 (MIRN193 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (NEAT1 long non-coding RNA, human) RN - 0 (RNA, Long Noncoding) RN - 0 (SOX5 protein, human) RN - 0 (SOXD Transcription Factors) SB - IM MH - Apoptosis MH - Cartilage, Articular/*metabolism/pathology MH - Cells, Cultured MH - Chondrocytes/*metabolism/pathology MH - Extracellular Matrix/metabolism MH - Humans MH - Inflammation/metabolism MH - MicroRNAs/*metabolism MH - Osteoarthritis, Knee/metabolism/*pathology MH - RNA, Long Noncoding/*metabolism MH - SOXD Transcription Factors/*metabolism MH - Signal Transduction OTO - NOTNLM OT - NEAT1 OT - SOX5 OT - chondrocytes OT - miR-193a-3p OT - osteoarthritis EDAT- 2019/12/24 06:00 MHDA- 2020/11/20 06:00 CRDT- 2019/12/24 06:00 PHST- 2019/06/15 00:00 [received] PHST- 2019/12/21 00:00 [accepted] PHST- 2019/12/24 06:00 [pubmed] PHST- 2020/11/20 06:00 [medline] PHST- 2019/12/24 06:00 [entrez] AID - 10.1002/cbin.11291 [doi] PST - ppublish SO - Cell Biol Int. 2020 Apr;44(4):947-957. doi: 10.1002/cbin.11291. Epub 2020 Jan 7.