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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/38574

Title: The impact of polyphenols on chondrocyte growth and survival: a preliminary report
Authors: Fernández-Arroyo, Salvador
Huete-Toral, Fernando
Pérez de Lara, María Jesús
Cádiz-Gurrea, María de la Luz
Legeai-Mallet, Laurence
Micol Molina, Vicente
Segura Carretero, Antonio
Joven, Jorge
Pintor, Jesús
Issue Date: 2015
Abstract: Background: Imbalances in the functional binding of fibroblast growth factors (FGFs) to their receptors (FGFRs) have consequences for cell proliferation and differentiation that in chondrocytes may lead to degraded cartilage. The toxic, proinflammatory, and oxidative response of cytokines and FGFs can be mitigated by dietary polyphenols. Objective: We explored the possible effects of polyphenols in the management of osteoarticular diseases using a model based on the transduction of a mutated human FGFR3 (G380R) in murine chondrocytes. This mutation is present in most cases of skeletal dysplasia and is responsible for the overexpression of FGFR3 that, in the presence of its ligand, FGF9, results in toxic effects leading to altered cellular growth. Design: Different combinations of dietary polyphenols derived from plant extracts were assayed in FGFR3 (G380R) mutated murine chondrocytes, exploring cell survival, chloride efflux, extracellular matrix (ECM) generation, and grade of activation of mitogen-activated protein kinases. Results: Bioactive compounds from Hibiscus sabdariffa reversed the toxic effects of FGF9 and restored normal growth, suggesting a probable translation to clinical requests in humans. Indeed, these compounds activated the intracellular chloride efflux, increased ECM generation, and stimulated cell proliferation. The inhibition of mitogen-activated protein kinase phosphorylation was interpreted as the main mechanism governing these beneficial effects. Conclusions: These findings support the rationale behind the encouragement of the development of drugs that repress the overexpression of FGFRs and suggest the dietary incorporation of supplementary nutrients in the management of degraded cartilage.
Sponsorship: The authors are grateful for the constant support provided by the Hospital Universitari de Sant Joan and the Universitat Rovira i Virgili. Salvador Fernández-Arroyo is the recipient of a Sara Borrell grant (CD12/00672) from the Instituto de Salud Carlos III, Madrid, Spain. The authors also thank the Andalusian Regional Government Council of Innovation and Science for the Excellence Project P11-CTS-7625 and Generalitat Valenciana for the project PROMETEO/2012/007. This work was also supported by projects of the Fundación Areces and the Fundación MAGAR.
Publisher: Co-Action Publishing
Keywords: Chondrodysplasia
Fibroblast growth factor
Hibiscus sabdariffa
Nutrition
Osteoarthritis
Polyphenols
Signaling pathways
URI: http://hdl.handle.net/10481/38574
ISSN: 1654-6628
1654-661X
Citation: Fernández-Arroyo, S.; et al. The impact of polyphenols on chondrocyte growth and survival: a preliminary report. Food and Nutrition Research, 59: 29311 (2015). [http://hdl.handle.net/10481/38574]
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