title: Hydroxytyrosol prevents increase of osteoarthritis markers in human chondrocytes treated with hydrogen peroxide or growth-related oncogene α.
abstract: Hydroxytyrosol (HT), a phenolic compound mainly derived from olives, has been proposed as a nutraceutical useful in prevention or treatment of degenerative diseases. In the present study we have evaluated the ability of HT to counteract the appearance of osteoarthritis (OA) features in human chondrocytes. Pre-treatment of monolayer cultures of chondrocytes with HT was effective in preventing accumulation of reactive oxidant species (ROS), DNA damage and cell death induced by H2O2 exposure, as well as the increase in the mRNA level of pro-inflammatory, matrix-degrading and hypertrophy marker genes, such as iNOS, COX-2, MMP-13, RUNX-2 and VEGF. HT alone slightly enhanced ROS production, but did not enhance cell damage and death or the expression of OA-related genes. Moreover HT was tested in an in vitro model of OA, i.e. three-dimensional micromass cultures of chondrocytes stimulated with growth-related oncogene α (GROα), a chemokine involved in OA pathogenesis and known to promote hypertrophy and terminal differentiation of chondrocytes. In micromass constructs, HT pre-treatment inhibited the increases in caspase activity and the level of the messengers for iNOS, COX-2, MMP-13, RUNX-2 and VEGF elicited by GROα. In addition, HT significantly increased the level of SIRT-1 mRNA in the presence of GROα. In conclusion, the present study shows that HT reduces oxidative stress and damage, exerts pro-survival and anti-apoptotic actions and favourably influences the expression of critical OA-related genes in human chondrocytes treated with stressors promoting OA-like features.
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Facchini
authors.affiliation: Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cetrullo
authors.affiliation: Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: D'Adamo
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy; Laboratorio di Immunoreumatologia and Rigenerazione Tissutale/Laboratorio RAMSES, Istituti Ortopedici Rizzoli, Bologna, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Guidotti
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy; Laboratorio di Immunoreumatologia and Rigenerazione Tissutale/Laboratorio RAMSES, Istituti Ortopedici Rizzoli, Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Minguzzi
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy; Laboratorio di Immunoreumatologia and Rigenerazione Tissutale/Laboratorio RAMSES, Istituti Ortopedici Rizzoli, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Facchini
authors.affiliation: Laboratorio di Immunoreumatologia and Rigenerazione Tissutale/Laboratorio RAMSES, Istituti Ortopedici Rizzoli, Bologna, Italy.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Borzì
authors.affiliation: Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Flamigni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism*; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006984:Hypertrophy / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000975:Antioxidants; D054360:Chemokine CXCL1; D018836:Inflammation Mediators; D016877:Oxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C005975:3,4-dihydroxyphenylethanol; D006861:Hydrogen Peroxide; D010626:Phenylethyl Alcohol