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Abstract
Introduction: Osteoarthritis (OA) is a whole-joint disease where inflammation interplays with extracellular matrix mineralization in a cycle that leads to its degradation. The lack of effective preventing treatments and disease modifying agents, demands new therapeutic targets and development of effective drugs. Amentadione (YP), a meroditerpenoid extracted from the alga Cystoseira usneoides was previously shown to have anti-inflammatory and antioxidant activities [Citation1]. The main purpose of this study was to develop a close-to-the-in-vivo OA model, to evaluate the potential and mode of action of novel therapeutic agents. Also, we aim to evaluate the potential of YP as a novel therapeutic agent for OA, using the developed 3D OA model.
Materials and methods: Monocultures of articular cells [Citation2], cartilage ex vivo explants and co-cultures of cartilage explants with synoviocytes, were treated with YP and subjected to inflammatory/mineralizing conditions. OA gene markers and inflammatory mediators were analysed by qPCR and ELISA. Histological evaluation of cartilage explants was performed by von Kossa/hematoxylin and Alcian blue staining.
Results: YP was shown to reduce the inflammatory response in the articular primary cell system when subjected to mineralizing and inflammatory conditions. After establishment and characterization of an ex vivo OA co-culture model, YP was confirmed to be able to reduce the expression of OA gene markers of inflammation, cell differentiation, and matrix degradation (COX-2, IL-6, Col10, Runx2, MMP3) following stimulation with hydroxyapatite and IL1-b.
Discussion and conclusions: YP pre-treatment of OA culture model systems resulted in a significant downregulation of inflammatory, differentiation, and extracellular matrix-related genes and reduced the levels of inflammatory cytokines. These results clearly indicate a protective effect of YP on cartilage degradation with high potential for OA therapeutic application.
Acknowledgements
The authors would like to acknowledge Portuguese Science and Technology Foundation (FCT) for the grant SFRH/BD/111824/2015 and the plurianual funding UID/Multi/04326/2013.