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Role of microRNA-449a on IL-1β-induced inflammatory responses in human chondrocytes
DC Field | Value | Language |
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dc.contributor.author | 박기원 | - |
dc.date.accessioned | 2017-07-11T16:10:21Z | - |
dc.date.available | 2017-07-11T16:10:21Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/149130 | - |
dc.description | Dept. of Medical Science/석사 | - |
dc.description.abstract | SIRT1 has anti-inflammatory as well as protective effects in chondrocytes. The object of this study was to investigate whether microRNA-449a regulates expression of SIRT1, which inhibits expression of catabolic genes in IL-1β-induced cartilage destruction. MicroRNA-449a expression was determined in OA chondrocytes and IL-1β-induced chondrocytes by real-time PCR. MicroRNA-449a binding sites on the 3'-UTR of SIRT1 mRNA and binding site conservation were examined using microRNA target prediction tools. SIRT1-overexpressing or knockdown chondrocytes were transfected with microRNA-449a mimic or anti-microRNA-449a mimic and stimulated by IL-1β. Expression of catabolic and anabolic genes was examined by real-time PCR and western blotting. Finally, positive effects of anti-microRNA-449a on expression of these genes were confirmed by western analysis of OA chondrocytes. Expression of microRNA-449a was increased in OA chondrocytes and IL-1β-induced chondrocytes. MMP-13 expression was enhanced, whereas type II collagen and SIRT1 expression were decreased in IL-1β-induced chondrocytes. SIRT1 overexpression resulted in decreased expression of catabolic genes, such as MMPs and ADAMTSs in response to IL-1β, but these effects were moderated by microRNA-449a. Suppression of microRNA-449a by anti-microRNA-449a inhibited expression of catabolic genes despite IL-1β stimulation, but these effects were abolished in SIRT1 knockdown chondrocytes. Furthermore, expression of catabolic genes was decreased and expression of type II collagen as well as SIRT1 was restored by anti-microRNA-449a in OA chondrocytes as well as in IL-1β-induced chondrocytes. Taken together, silencing of microRNA-449a had a protective effect, inhibiting catabolic gene expression and restoring anabolic gene expression, by targeting SIRT1 in IL-1β-induced cartilage destruction | - |
dc.description.statementOfResponsibility | open | - |
dc.publisher | Graduate School, Yonsei University | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Role of microRNA-449a on IL-1β-induced inflammatory responses in human chondrocytes | - |
dc.title.alternative | 사람 연골세포의 IL-1β 에 의한 염증 반응에서 microRNA-449a 의 역할 | - |
dc.type | Thesis | - |
dc.contributor.alternativeName | Park, Ki Won | - |
dc.type.local | Thesis | - |
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