title: Hydroxytyrosol prevents chondrocyte death under oxidative stress by inducing autophagy through sirtuin 1-dependent and -independent mechanisms.
abstract: BACKGROUND
  Hydroxytyrosol (HT), a major phenolic antioxidant found in olive oil, can afford protection from oxidative stress in several types of non-tumoral cells, including chondrocytes. Autophagy was recently identified as a protective process during osteoarthritis (OA) development and critical for survival of chondrocytes. Therefore we have investigated the possibility to modulate chondrocyte autophagy by HT treatment.
  
  
  METHODS
  DNA damage and cell death were estimated in human C-28/I2 and primary OA chondrocytes exposed to hydrogen peroxide. Autophagic flux and mitophagy were monitored by measuring levels and location of autophagy markers through western blot, immunostaining and confocal laser microscopy. Late autophagic vacuoles were stained with monodansylcadaverine. The involvement of sirtuin 1 (SIRT-1) was evaluated by immunohistochemistry, western blot and gene silencing with specific siRNA.
  
  
  RESULTS
  HT increases markers of autophagy and protects chondrocytes from DNA damage and cell death induced by oxidative stress. The protective effect requires the deacetylase SIRT-1, which accumulated in the nucleus following HT treatment. In fact silencing of this enzyme prevented HT from promoting the autophagic process and cell survival. Furthermore HT supports autophagy even in a SIRT-1-independent manner, by increasing p62 transcription, required for autophagic degradation of polyubiquitin-containing bodies.
  
  
  CONCLUSIONS
  These results support the potential of HT as a chondroprotective nutraceutical compound against OA, not merely for its antioxidant ability, but as an autophagy and SIRT-1 inducer as well.
  
  
  CONCLUSIONS
  HT may exert a cytoprotective action by promoting autophagy in cell types that may be damaged in degenerative diseases by oxidative and other stress stimuli.
authors.affiliation: Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cetrullo
authors.affiliation: Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, via Irnerio 48, 40126 Bologna, Italy; Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, via Massarenti 9, 40136 Bologna, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: D'Adamo
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, via Massarenti 9, 40136 Bologna, Italy; Laboratorio di Immunoreumatologia and Rigenerazione Tissutale/Laboratorio RAMSES, Istituto Ortopedico Rizzoli, via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Guidotti
authors.affiliation: Laboratorio di Immunoreumatologia and Rigenerazione Tissutale/Laboratorio RAMSES, Istituto Ortopedico Rizzoli, via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Borzì
authors.affiliation: Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, via Irnerio 48, 40126 Bologna, Italy. Electronic address: flavio.flamigni@unibo.it.
authors.forename: Flavio
authors.initials: F
authors.lastname: Flamigni
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects*; D019610:Cytoprotection; D004249:DNA Damage; D006801:Humans; D010003:Osteoarthritis / Q000188:drug therapy; D018384:Oxidative Stress; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D056564:Sirtuin 1 / Q000502:physiology*
chemical_list: C005975:3,4-dihydroxyphenylethanol; D056564:Sirtuin 1; D010626:Phenylethyl Alcohol
keywords: Autophagy; Chondrocyte; Hydroxytyrosol; Osteoarthritis; Oxidative stress; SIRT-1