title: The impact of polyphenols on chondrocyte growth and survival: a preliminary report.
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.
  
  
  METHODS
  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.
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, IISPV, Universitat Rovira i Virgili, Reus, Spain.|Campus of International Excellence Southern Catalonia, Tarragona, Spain; sfernandez@fiispv.cat.
authors.forename: Salvador
authors.initials: S
authors.lastname: Fernández-Arroyo
authors.affiliation: Department of Biochemistry, Faculty of Optics and Optometry, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Huete-Toral
authors.affiliation: Department of Biochemistry, Faculty of Optics and Optometry, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Pérez de Lara
authors.affiliation: Functional Food Research and Development Center, Health Science Technological Park, Granada, Spain.|Department of Analytical Chemistry, University of Granada, Granada, Spain.
authors.forename: María
authors.initials: M
authors.lastname: de la Luz Cádiz-Gurrea
authors.affiliation: Imagine Institute - INSERM U1163, Necker Hospital for Sick Children, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Legeai-Mallet
authors.affiliation: Institute of Molecular and Cell Biology, Miguel Hernández University, Elche, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Micol
authors.affiliation: Functional Food Research and Development Center, Health Science Technological Park, Granada, Spain.|Department of Analytical Chemistry, University of Granada, Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Segura-Carretero
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, IISPV, Universitat Rovira i Virgili, Reus, Spain.|Campus of International Excellence Southern Catalonia, Tarragona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
authors.affiliation: Department of Biochemistry, Faculty of Optics and Optometry, Universidad Complutense de Madrid, Madrid, Spain; jpintor@vet.ucm.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pintor
keywords: Hibiscus sabdariffa; chondrodysplasia; fibroblast growth factor; nutrition; osteoarthritis; polyphenols; signaling pathways