Amentadione is a new modulating agent for osteoarthritis in an ex-vivo co-culture preclinical assay
| Autor: | Dina C. Simes, Ruben Martins Da Costa, Francisco J. Blanco, Eva Zubía, Joana Magalhães, Inês Perrolas, Carla Viegas, Acácio Ramos, Cees Vermeer, Nuna Araújo, Maria Miguel |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Osteoarthritis (OA)
Inflammation Chemistry General Medicine Osteoarthritis Free Communications Biology and Biochemistry 030204 cardiovascular system & hematology medicine.disease Mineralization (biology) 3. Good health Cell biology Calcification Extracellular matrix 03 medical and health sciences 0302 clinical medicine Amentadione (YP) medicine 030212 general & internal medicine medicine.symptom Co-culture Ex vivo |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP Ann Med |
| Popis: | Introduction: Osteoarthritis (OA) is a whole-joint disease where inflammation interplays with extracellular matrix mineralization in a cycle that leads to its degradation. The lack of effective preventing treatments and disease modifying agents, demands new therapeutic targets and development of effective drugs. Amentadione (YP), a meroditerpenoid extracted from the alga Cystoseira usneoides was previously shown to have anti-inflammatory and antioxidant activities [1]. The main purpose of this study was to develop a close-to-the-in-vivo OA model, to evaluate the potential and mode of action of novel therapeutic agents. Also, we aim to evaluate the potential of YP as a novel therapeutic agent for OA, using the developed 3D OA model. Materials and methods: Monocultures of articular cells [2], cartilage ex vivo explants and co-cultures of cartilage explants with synoviocytes, were treated with YP and subjected to inflammatory/mineralizing conditions. OA gene markers and inflammatory mediators were analysed by qPCR and ELISA. Histological evaluation of cartilage explants was performed by von Kossa/hematoxylin and Alcian blue staining. Results: YP was shown to reduce the inflammatory response in the articular primary cell system when subjected to mineralizing and inflammatory conditions. After establishment and characterization of an ex vivo OA co-culture model, YP was confirmed to be able to reduce the expression of OA gene markers of inflammation, cell differentiation, and matrix degradation (COX-2, IL-6, Col10, Runx2, MMP3) following stimulation with hydroxyapatite and IL1-b. Discussion and conclusions: YP pre-treatment of OA culture model systems resulted in a significant downregulation of inflammatory, differentiation, and extracellular matrix-related genes and reduced the levels of inflammatory cytokines. These results clearly indicate a protective effect of YP on cartilage degradation with high potential for OA therapeutic application. |
| Databáze: | OpenAIRE |
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