title: MicroRNA-155 suppresses autophagy in chondrocytes by modulating expression of autophagy proteins.
abstract: Autophagy dysfunction has been reported in osteoarthritis (OA) cartilage. The objective of this study was to investigate the role of microRNA-155 (miR-155), which is overexpressed in OA, in the regulation of autophagy in human chondrocytes.
  
  
  
  Rapamycin (50 nM) and 2-deoxyglucose (2-DG) (5 mM) were used to stimulate autophagy in primary human articular chondrocytes and in the T/C28a2 human chondrocyte cell line. Cells were transfected with LNA GapmeR or mimic specific for miR-155 and autophagy flux was assessed by LC3 western blotting and by Cyto-ID(®) dye quantification in autophagic vacuoles. Expression of predicted miR-155 targets in the autophagy pathway were analyzed by real-time PCR and western blotting.
  
  
  
  Autophagy flux induced by rapamycin and 2-DG was significantly increased by miR-155 LNA, and significantly decreased after miR-155 mimic transfection in T/C28a2 cells and in human primary chondrocytes. These effects of miR-155 on autophagy were related to suppression of gene and protein expression of key autophagy regulators including Ulk1, FoxO3, Atg14, Atg5, Atg3, Gabarapl1, and Map1lc3.
  
  
  
  MiR-155 is an inhibitor of autophagy in chondrocytes and contributes to the autophagy defects in OA.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA; Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.
authors.forename: S
authors.initials: S
authors.lastname: D'Adamo
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: O
authors.initials: O
authors.lastname: Alvarez-Garcia
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Muramatsu
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Flamigni
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA. Electronic address: mlotz@scripps.edu.
authors.forename: M K
authors.initials: MK
authors.lastname: Lotz
mesh_terms: D001343:Autophagy; D002358:Cartilage, Articular; D002478:Cells, Cultured; D019902:Chondrocytes; D006801:Humans; D035683:MicroRNAs; D010003:Osteoarthritis
chemical_list: D035683:MicroRNAs
keywords: Autophagy; Cartilage; Chondrocytes; microRNAs