RT journal article
T1 Amentadione from the Alga Cystoseira usneoides as a Novel Osteoarthritis Protective Agent in an Ex Vivo Co-Culture OA Model
A1 Araújo, Nuna
A1 Viegas, Carla S. B.
A1 Zubía Mendoza, Eva
A1 Magalhães, Joana
A1 Ramos, Acácio
A1 Carvalho, Maria M.
A1 Cruz, Henrique
A1 Sousa, João Paulo
A1 Blanco, Francisco J.
A1 Vermeer, Cees
A1 Simes, Dina C.
A2 Química Orgánica
K1 osteoarthritis
K1 amentadione
K1 preclinical osteoarthritis models
K1 marine compounds
K1 Cystoseira usneoides
K1 inflammation
K1 mineralization
K1 chondrocytes
K1 synoviocytes
K1 cartilage explants
AB 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-1 beta (IL-1 beta) 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-kappa B gene expression and decreased phosphorylated IkB alpha/total IkB alpha 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-kappa B signaling pathways, with high therapeutic potential.
PB MDPI
SN 1660-3397
YR 2020
FD 2020-12
LK http://hdl.handle.net/10498/24368
UL http://hdl.handle.net/10498/24368
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 11-nov-2026