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Inhibition of microRNA-449a prevents IL-1β-induced cartilage destruction via SIRT1

 K.W. Park  ;  K.-M. Lee  ;  D.S. Yoon  ;  K.H. Park  ;  W.J. Choi  ;  J.W. Lee  ;  S.-H. Kim 
 Osteoarthritis and Cartilage, Vol.24(12) : 2153-2161, 2016 
Journal Title
 Osteoarthritis and Cartilage 
Issue Date
OBJECTIVE: 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. MATERIALS AND METHODS: 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 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. RESULTS: 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. CONCLUSION: 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.
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1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
김성환(Kim, Sung Hwan) ORCID logo https://orcid.org/0000-0001-5743-6241
박광환(Park, Kwang Hwan) ORCID logo https://orcid.org/0000-0002-2110-0559
이경미(Lee, Kyoung Mi) ORCID logo https://orcid.org/0000-0002-9038-8162
이진우(Lee, Jin Woo) ORCID logo https://orcid.org/0000-0002-0293-9017
최우진(Choi, Woo Jin)
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