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

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2153-2161
Number of pages9
JournalOsteoarthritis and Cartilage
Volume24
Issue number12
DOIs
Publication statusPublished - 2016 Dec 1

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Biomedical Engineering
  • Orthopedics and Sports Medicine

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