dc.creator | Papathanasiou I., Trachana V., Mourmoura E., Tsezou A. | en |
dc.date.accessioned | 2023-01-31T09:44:36Z | |
dc.date.available | 2023-01-31T09:44:36Z | |
dc.date.issued | 2019 | |
dc.identifier | 10.1016/j.lfs.2019.05.018 | |
dc.identifier.issn | 00243205 | |
dc.identifier.uri | http://hdl.handle.net/11615/77835 | |
dc.description.abstract | Aims: Previous studies have demonstrated that transcriptional silencing of miRNAs due to DNA hypermethylation is associated with different pathologies. It has also been reported that abnormal expression of miR-140-5p and miR-146a is linked to osteoarthritis (OA)progression. In this study, we investigated the role of DNA methylation on miR-140-5p and miR-146a expression in OA. Main methods: miR-140-5p and miR-146a expression was investigated by qRT-PCR. The methylation status of miR-140 and miR-146a regulatory regions was analyzed using qMSP and bisulfite sequencing analysis. SMAD-3 and NF-kB binding to miR-140 and miR-146a regulatory regions was assessed by ChIP assay and knockdown experiments. OA-related genes' expression was evaluated in 5-AzadC, miRNAs inhibitor and 5-AzadC/miRNAs inhibitor-treated cells. Key findings: Hypermethylation of specific CpG sites in miR-140 and miR-146a regulatory regions was associated with downregulation of miR-140-5p and miR-146a in OA chondrocytes and synoviocytes, respectively. 5-AzadC-induced miR-140-5p and miR-146a upregulation was observed in OA chondrocytes and synoviocytes. Moreover, we found decreased binding affinity of SMAD-3 and NF-kB transcription factors on the hypermethylated miR-140-5p and miR-146a regulatory regions, respectively. Downregulation of MMP-13 and ADAMTS-5 in 5-AzadC-treated OA chondrocytes was prevented by miR-140-5p inhibitor transfection. Similarly, 5-AzadC-treated OA synoviocytes showed decreased expression of IRAK-1, IL1Β and IL-6, which was reversed following 5-AzadC-/miR-146a inhibitor treatment. Significance: Our results strongly suggest the impact of DNA methylation on miR-140-5p and miR-146a suppression in OA chondrocytes and synoviocytes, contributing to OA pathogenesis. © 2019 Elsevier Inc. | en |
dc.language.iso | en | en |
dc.source | Life Sciences | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85065540723&doi=10.1016%2fj.lfs.2019.05.018&partnerID=40&md5=1842c757459d00defc44108c21e9498c | |
dc.subject | aggrecanase 2 | en |
dc.subject | azacitidine | en |
dc.subject | bisulfite | en |
dc.subject | collagenase 3 | en |
dc.subject | immunoglobulin enhancer binding protein | en |
dc.subject | interleukin 1 receptor associated kinase 1 | en |
dc.subject | interleukin 1beta | en |
dc.subject | interleukin 6 | en |
dc.subject | microRNA | en |
dc.subject | microRNA 140 | en |
dc.subject | microRNA 140 5p | en |
dc.subject | microRNA 146a | en |
dc.subject | Smad3 protein | en |
dc.subject | unclassified drug | en |
dc.subject | microRNA | en |
dc.subject | Mirn140 microRNA, human | en |
dc.subject | MIRN146 microRNA, human | en |
dc.subject | aged | en |
dc.subject | Article | en |
dc.subject | binding affinity | en |
dc.subject | chondrocyte | en |
dc.subject | chromatin immunoprecipitation | en |
dc.subject | clinical article | en |
dc.subject | controlled study | en |
dc.subject | CpG island | en |
dc.subject | DNA methylation | en |
dc.subject | DNA sequence | en |
dc.subject | down regulation | en |
dc.subject | female | en |
dc.subject | gene control | en |
dc.subject | gene expression | en |
dc.subject | gene knockdown | en |
dc.subject | human | en |
dc.subject | human cell | en |
dc.subject | human tissue | en |
dc.subject | male | en |
dc.subject | methylation specific polymerase chain reaction | en |
dc.subject | osteoarthritis | en |
dc.subject | pathogenesis | en |
dc.subject | polymerase chain reaction | en |
dc.subject | promoter region | en |
dc.subject | protein binding | en |
dc.subject | protein expression | en |
dc.subject | quantitative analysis | en |
dc.subject | real time polymerase chain reaction | en |
dc.subject | synoviocyte | en |
dc.subject | transcription regulation | en |
dc.subject | upregulation | en |
dc.subject | cell culture | en |
dc.subject | gene expression regulation | en |
dc.subject | genetics | en |
dc.subject | metabolism | en |
dc.subject | middle aged | en |
dc.subject | osteoarthritis | en |
dc.subject | pathology | en |
dc.subject | very elderly | en |
dc.subject | Aged | en |
dc.subject | Aged, 80 and over | en |
dc.subject | Cells, Cultured | en |
dc.subject | Chondrocytes | en |
dc.subject | CpG Islands | en |
dc.subject | DNA Methylation | en |
dc.subject | Gene Expression Regulation | en |
dc.subject | Humans | en |
dc.subject | MicroRNAs | en |
dc.subject | Middle Aged | en |
dc.subject | Osteoarthritis | en |
dc.subject | Synoviocytes | en |
dc.subject | Elsevier Inc. | en |
dc.title | DNA methylation regulates miR-140-5p and miR-146a expression in osteoarthritis | en |
dc.type | journalArticle | en |