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PLoS One. 2014 Oct 3;9(10):e109724. doi: 10.1371/journal.pone.0109724. eCollection 2014.

Hydroxytyrosol prevents increase of osteoarthritis markers in human chondrocytes treated with hydrogen peroxide or growth-related oncogene α.

Author information

1
Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.
2
Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.
3
Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy; Laboratorio di Immunoreumatologia and Rigenerazione Tissutale/Laboratorio RAMSES, Istituti Ortopedici Rizzoli, Bologna, Italy.
4
Laboratorio di Immunoreumatologia and Rigenerazione Tissutale/Laboratorio RAMSES, Istituti Ortopedici Rizzoli, Bologna, Italy.

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.

PMID:
25279550
PMCID:
PMC4184903
DOI:
10.1371/journal.pone.0109724
[Indexed for MEDLINE]
Free PMC Article

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