Abstract
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.
Original language | English |
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Article number | 624 |
Number of pages | 16 |
Journal | Marine Drugs |
Volume | 18 |
Issue number | 12 |
DOIs | |
Publication status | Published - Dec 2020 |
Keywords
- osteoarthritis
- amentadione
- preclinical osteoarthritis models
- marine compounds
- Cystoseira usneoides
- inflammation
- mineralization
- chondrocytes
- synoviocytes
- cartilage explants
- INFLAMMATION
- PATHOGENESIS
- CALCIFICATION
- ANTIOXIDANT
- PREVALENCE
- PROTEIN
- RICH