Abstract

Background Osteoarthritis (OA) is a degenerative disease of the joints characterised by the imbalance of anabolic and catabolic processes in articular cartilage. It is one of the most significant causes of disability in the world affecting over 60% of people over the age of 60, causing joint stiffness, pain and a decrease in the quality of life. Currently no successful disease-modifying agent has been found to prevent or treat the condition. To address this unmet need, alternative approaches, including the use of nutraceuticals as a novel therapeutic intervention are under examination. Objectives To analyse if nutraceutical are able to reverse the catabolic activity that contribute to cartilage destruction in OA. Here two polyphenols from extra virgin olive oil (EVOO), oleocanthal (OLC) and ligstroside aglycone (LA), plus a chemically modified acetylated ligstroside aglycone (A-LA), and two marine polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were examined as potential anti-inflammatory agents for OA. Methods Human chondrocytes and cartilage explants were extracted from OA femoral heads, cultured and incubated with increasing concentrations of select compounds in combination with the pro-inflammatory cytokines IL-1β and oncostatin M (OSM). Gene expression levels were analysed by qPCR; nitric oxide (NO), GAG release and cytokines were measured in supernatants by colorimetric assays and Luminex technology respectively. Safranin-O and Alcian blue/Sirius red staining were done to quantify extracellular matrix components from cartilage. Results Acetylated ligstroside showed the most promising results for implementation in treating OA as it reduced the expression of pro-inflammatory genes such as inducible nitric oxide (iNOS), matrix metalloprotease-13 (MMP13) and interleukin-1β (IL1B) at both RNA and protein levels; decreased nitric oxide (NO) levels from cartilage explants and also reduced proteoglycan (PG) losses in human osteoarthritic cartilage explants and chondrocytes (Figure 1). Conclusion These results substantiate the role of nutraceuticals in OA with implications for therapeutic intervention and our understanding of OA pathophysiology.

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