Journal
ARTHRITIS AND RHEUMATISM
Volume 62, Issue 6, Pages 1675-1682Publisher
WILEY
DOI: 10.1002/art.27437
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Funding
- Instituto de Salud Carlos III [RD08/0075 [RIER]]
- University of Santiago de Compostela [GI-1957]
- Italian Ministry of Education, Research and University
- Xunta de Galicia (SERGAS) [PI08/0040, PGIDIT07PXIB918090PR]
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Objective. In joint diseases, cartilage homeostasis is disrupted by mechanisms that are driven by combinations of biologic factors that vary according to the disease process. In osteoarthritis (OA), biomechanical stimuli predominate, with up-regulation of both catabolic and anabolic factors. Likewise, OA progression is characterized by increased nitric oxide ( NO) production, which has been associated with cartilage degradation. Given the relevance of cartilage degenerative diseases in our society, the development of a novel pharmacologic intervention is a critically important public health goal. Recently, oleocanthal isolated from extra virgin olive oil was found to display nonsteroidal antiinflammatory drug activity similar to that of ibuprofen, a drug widely used in the therapeutic management of joint inflammatory diseases. We undertook this study to evaluate the effect of oleocanthal and its derivatives on the modulation of NO production in chondrocytes. Methods. Cultured ATDC-5 chondrocytes were tested with different doses of oleocanthal and its derivatives. Cell viability was evaluated using the MTT assay. Nitrite accumulation was determined in culture supernatant using the Griess reaction. Inducible NO synthase (NOS2) protein expression was examined using Western blotting analysis. Results. Oleocanthal and its derivatives decreased lipopolysaccharide-induced NOS2 synthesis in chondrocytes without significantly affecting cell viability at lower concentrations. Among the derivatives we examined, derivative 231 was the most interesting, since its inhibitory effect on NOS2 was devoid of cytotoxicity even at higher concentrations. Conclusion. This class of molecules shows potential as a therapeutic weapon for the treatment of inflammatory degenerative joint diseases.
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