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.
Highlights
Chondrocytes, the only cell type in adult cartilage, are usually kept in a quiescent, maturation-arrested state, and maintain tissue integrity by a low turnover of extra-cellular matrix (ECM) components
Effects of hydroxytyrosol on human chondrocytes treated with hydrogen peroxide Articular chondrocytes from OA patients were cultured in monolayer and treated with H2O2 to induce oxidative stress
Initial reports attributed the beneficial properties of olive oil to its composition of fatty acids with the high content of oleic acid, accumulating evidence indicates that its minor components, polyphenols, critically contribute to these health benefits
Summary
Chondrocytes, the only cell type in adult cartilage, are usually kept in a quiescent, maturation-arrested state, and maintain tissue integrity by a low turnover of extra-cellular matrix (ECM) components. At the time indicated after H2O2, cells were harvested and analysed by qRT-PCR for the amount of COX-2 mRNA (A), iNOS mRNA (B), MMP-13 mRNA (C), RUNX-2 mRNA (D), VEGF mRNA (E) and SIRT-1 mRNA (F).
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