Amentadione from the Alga Cystoseira usneoides as a Novel Osteoarthritis Protective Agent in an Ex Vivo Co-Culture OA Model
Identificadores
Identificadores
URI: http://hdl.handle.net/20.500.11940/16223
PMID: 33297528
DOI: 10.3390/md18120624
ISSN: 1660-3397
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Fecha de publicación
2020Título de revista
Marine Drugs
Tipo de contenido
Journal Article
DeCS
Cyanobacteria | expresión génica | inflamación | antirreumáticos | condrocitos | técnicas de cocultivo | diterpenos | cartílago | cultivo celular primario | durapatita | humanos | interleucina-1beta | antiinflamatorios | osteoartritisMeSH
Gene Expression | Anti-Inflammatory Agents | Chondrocytes | Diterpenes | Coculture Techniques | Osteoarthritis | Cyanobacteria | Humans | Antirheumatic Agents | Durapatite | Primary Cell Culture | Interleukin-1beta | Inflammation | CartilageResumen
Osteoarthritis (OA) remains a prevalent chronic disease without effective prevention and treatment. Amentadione (YP), a meroditerpenoid purified from the alga Cystoseira usneoides, has demonstrated anti-inflammatory activity. Here, we investigated the YP anti-osteoarthritic potential, by using a novel OA preclinical drug development pipeline designed to evaluate the anti-inflammatory and anti-mineralizing activities of potential OA-protective compounds. The workflow was based on in vitro primary cell cultures followed by human cartilage explants assays and a new OA co-culture model, combining cartilage explants with synoviocytes under interleukin-1beta (IL-1beta) or hydroxyapatite (HAP) stimulation. A combination of gene expression analysis and measurement of inflammatory mediators showed that the proposed model mimicked early disease stages, while YP counteracted inflammatory responses by downregulation of COX-2 and IL-6, improved cartilage homeostasis by downregulation of MMP3 and the chondrocytes hypertrophic differentiation factors Col10 and Runx2. Importantly, YP downregulated NF-kappaB gene expression and decreased phosphorylated IkBalpha/total IkBalpha ratio in chondrocytes. These results indicate the co-culture as a relevant pre-clinical OA model, and strongly suggest YP as a cartilage protective factor by inhibiting inflammatory, mineralizing, catabolic and differentiation processes during OA development, through inhibition of NF-kappaB signaling pathways, with high therapeutic potential.