title: Silencing microRNA-34a inhibits chondrocyte apoptosis in a rat osteoarthritis model in vitro.
abstract: OBJECTIVE
  miRNAs, which are non-coding RNAs, play a role in the pathogenesis of disease including OA. miRNA (miR)-34a is induced by p53, subsequently leading to cell apoptosis, which is one of the major factors in the pathogenesis of OA. The purpose of this study is to investigate the effect of silencing miR-34a on IL-1β-induced chondrocyte apoptosis in a rat OA model in vitro.
  
  
  METHODS
  Locked nucleotide analogue (LNA)-modified miR-34a-specific anti-sense was transfected into rat chondrocyte monolayer culture. After that, IL-1β was added to the chondrocytes to create an OA model in vitro. The effect of silencing miR-34a on the prevention of chondrocyte apoptosis was analysed by assessment of the expression levels of Col2a1 and iNOS, also through assessment of cell viability and TUNEL staining.
  
  
  RESULTS
  The expression of miR-34a was significantly up-regulated by IL-1β. Silencing of miR-34a significantly prevented IL-1β-induced down-regulation of Col2a1, as well as IL-1β-induced up-regulation of iNOS. Finally, MiR-34a inhibitor could also reduce TUNEL-positive cells.
  
  
  CONCLUSIONS
  Silencing of miR-34a by LNA-modified anti-sense could effectively reduce rat chondrocyte apoptosis induced by IL-1β. This present study revealed that silencing of miR-34a might develop a novel intervention for OA treatment through the prevention of cartilage degradation.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Abouheif
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nakasa
authors.forename: Hayatoshi
authors.initials: H
authors.lastname: Shibuya
authors.forename: Takuya
authors.initials: T
authors.lastname: Niimoto
authors.forename: Wirat
authors.initials: W
authors.lastname: Kongcharoensombat
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ochi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics*; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs