The impact of polyphenols on chondrocyte growth and survival: a preliminary report
Sammanfattning
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.