Amentadione from the alga Cystoseira usneoides as a novel osteoarthritis trotective agent in an ex vivo co-culture OA Model

• Autor(a) principal: Araujo, Nuna C. P.
• Data de Publicação: 2020
• Outros Autores: Viegas, Carla, Zubía, Eva, Magalhães, Joana, Ramos, Acácio, Carvalho, Maria M., Cruz, Henrique, Sousa, João Paulo, Blanco, Francisco J., Vermeer, Cees, Simes, Dina
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.1/14964
• topic: Chondrocytes; Cartilage explants; Osteoarthritis; Amentadione; Preclinical osteoarthritis models; Marine compounds; Cystoseira usneoides; Inflammation; Mineralization; Synoviocytes

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-1β (IL-1β) 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-κB gene expression and decreased phosphorylated IkBα/total IkBα 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-κB signaling pathways, with high therapeutic potential.