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Titre du document / Document title

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

Auteur(s) / Author(s)

WATTEL Alice ; KAMEL Said ; PROUILLET Christophe ; PETIT Jean-Pierre ; LORGET Florence ; OFFORD Elizabeth ; BRAZIER Michel ;

Résumé / 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. NFKB 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 NFKB and AP-1.

Revue / Journal Title

Journal of cellular biochemistry    ISSN  0730-2312   CODEN JCEBD5 

Source / Source

2004, vol. 92, no2, pp. 285-295 [11 page(s) (article)]

Langue / Language

Anglais

Editeur / Publisher

Wiley-Liss, Hoboken, NJ, ETATS-UNIS  (1982) (Revue)

Localisation / Location

INIST-CNRS, Cote INIST : 16565, 35400011192565.0070

Nº notice refdoc (ud4) : 15743200



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