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Open AccessArticle

Amentadione from the Alga Cystoseira usneoides as a Novel Osteoarthritis Protective Agent in an Ex Vivo Co-Culture OA Model

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Centre of Marine Sciences (CCMAR), University of Algarve, 8005-139 Faro, Portugal
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GenoGla Diagnostics, Centre of Marine Sciences (CCMAR), University of Algarve, 8005-139 Faro, Portugal
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Department of Organic Chemistry, Faculty of Marine and Environmental Sciences, University of Cadiz, 11510 Puerto Real (Cádiz), Spain
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Unidad de Medicina Regenerativa, Grupo de Investigación en Reumatología (GIR), Instituto de Investigación Biomédica de A Coruña (INIBIC), Complejo Hospitalario Universitario de A Coruña (CHUAC), Sergas, 15006 A Coruña, Spain
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Agrupación Estratégica CICA-INIBIC, Universidade da Coruña (UDC), 15006 A Coruña, Spain
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Centro de Investigación Biomédica en Red (CIBER), 28029 Madrid, Spain
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Department of Orthopedics and Traumatology, Hospital Particular do Algarve (HPA), 8005-226 Gambelas-Faro, Portugal
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Cardiovascular Research Institute CARIM, Maastricht University, 6229 EV Maastricht, The Netherlands
*
Author to whom correspondence should be addressed.
Mar. Drugs 2020, 18(12), 624; https://doi.org/10.3390/md18120624
Received: 12 November 2020 / Revised: 27 November 2020 / Accepted: 3 December 2020 / Published: 7 December 2020
(This article belongs to the Special Issue Selected Papers from XVI MaNaPro and XI ECMNP)
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. View Full-Text
Keywords: osteoarthritis; amentadione; preclinical osteoarthritis models; marine compounds; Cystoseira usneoides; inflammation; mineralization; chondrocytes; synoviocytes; cartilage explants osteoarthritis; amentadione; preclinical osteoarthritis models; marine compounds; Cystoseira usneoides; inflammation; mineralization; chondrocytes; synoviocytes; cartilage explants
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MDPI and ACS Style

Araújo, N.; Viegas, C.S.B.; Zubía, E.; Magalhães, J.; Ramos, A.; Carvalho, M.M.; Cruz, H.; Sousa, J.P.; Blanco, F.J.; Vermeer, C.; Simes, D.C. Amentadione from the Alga Cystoseira usneoides as a Novel Osteoarthritis Protective Agent in an Ex Vivo Co-Culture OA Model. Mar. Drugs 2020, 18, 624. https://doi.org/10.3390/md18120624

AMA Style

Araújo N, Viegas CSB, Zubía E, Magalhães J, Ramos A, Carvalho MM, Cruz H, Sousa JP, Blanco FJ, Vermeer C, Simes DC. Amentadione from the Alga Cystoseira usneoides as a Novel Osteoarthritis Protective Agent in an Ex Vivo Co-Culture OA Model. Marine Drugs. 2020; 18(12):624. https://doi.org/10.3390/md18120624

Chicago/Turabian Style

Araújo, Nuna; Viegas, Carla S.B.; Zubía, Eva; Magalhães, Joana; Ramos, Acácio; Carvalho, Maria M.; Cruz, Henrique; Sousa, João P.; Blanco, Francisco J.; Vermeer, Cees; Simes, Dina C. 2020. "Amentadione from the Alga Cystoseira usneoides as a Novel Osteoarthritis Protective Agent in an Ex Vivo Co-Culture OA Model" Mar. Drugs 18, no. 12: 624. https://doi.org/10.3390/md18120624

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