Journal of Cellular Biochemistry

Flavonoid quercetin decreases osteoclastic differentiation induced by RANKL via a mechanism involving NFκB and AP-1

Authors

  • Alice Wattel,

    Corresponding author
    1. Unité de Recherche sur les Mécanismes de la Résorption Osseuse, Laboratoire de Pharmacie Clinique, Université de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France
    • Unité de Recherche sur les Mécanismes de la Résorption Osseuse, Laboratoire de Pharmacie Clinique, Université de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France.
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  • Said Kamel,

    1. Unité de Recherche sur les Mécanismes de la Résorption Osseuse, Laboratoire de Pharmacie Clinique, Université de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France
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  • Christophe Prouillet,

    1. Unité de Recherche sur les Mécanismes de la Résorption Osseuse, Laboratoire de Pharmacie Clinique, Université de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France
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  • Jean-Pierre Petit,

    1. Unité de Recherche sur les Mécanismes de la Résorption Osseuse, Laboratoire de Pharmacie Clinique, Université de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France
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  • Florence Lorget,

    1. Department of Nutrition, Nestlé Research Center, Vers-chez-les-Blanc, 1000 Lausanne 26, Switzerland
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  • Elizabeth Offord,

    1. Department of Nutrition, Nestlé Research Center, Vers-chez-les-Blanc, 1000 Lausanne 26, Switzerland
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  • Michel Brazier

    1. Unité de Recherche sur les Mécanismes de la Résorption Osseuse, Laboratoire de Pharmacie Clinique, Université de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France
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Abstract

Flavonoids are micronutrients widely present in food of plant origin. They have been attributed pharmacological properties such as anticancer and prevention of age-related pathologies. It has been recently hypothesized that flavonoids increase bone mass and prevent osteoporosis. However, little is known about the in vitro effects of flavonoids on osteoclast activities. We investigated the effects of quercetin, one of the most commonly occurring flavonoids, on osteoclast differentiation which is a critical determinant step of in vivo bone resorption. Two in vitro models of osteoclast differentiation were used in this study: a murine one, involving the culture of RAW 264.7 cells in presence of receptor activator of NFκB ligand (RANKL), and a human model consisting of differentiating peripheral blood monocytic cells (PBMC) isolated from peripheral blood in presence of RANKL and macrophage-colony stimulating factor (M-CSF). Osteoclastogenesis was assessed by osteoclast-like number, tartrate resistant acid phosphatase (TRAP) activity, and bone resorbing activity. We showed that quercetin (0.1–10 μM) decreased osteoclastogenesis in a dose dependent manner in both models with significant effects observed at low concentrations, from 1 to 5 μM. The IC50 value was about 1 μM. Analysis of protein–DNA interaction by electrophoretic mobility shift assay (EMSA) performed on RAW cells showed that a pre-treatment with quercetin inhibited RANKL-induced nuclear factor kB (NFκB) and activator protein 1 (AP-1) activation. NFκB and AP-1 are transcription factors highly involved in osteoclastic differentiation and their inhibition could play an important role in the decrease of osteoclastogenesis observed in the presence of quercetin. In conclusion, the present results demonstrate for the first time that quercetin, a flavonoid characterized by antioxidant activities, is a potent inhibitor of in vitro osteoclastic differentiation, via a mechanism involving NFκB and AP-1. © 2004 Wiley-Liss, Inc.

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