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Flavonoid quercetin decreases osteoclastic differentiation induced by RANKL via a mechanism involving NF kappa B and AP-1.
J Cell Biochem. 2004 May 15; 92(2):285-95.JC

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 NF kappa B 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 microM) decreased osteoclastogenesis in a dose dependent manner in both models with significant effects observed at low concentrations, from 1 to 5 microM. The IC(50) value was about 1 microM. 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 (NF kappa B) and activator protein 1 (AP-1) activation. NF kappa B 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 NF kappa B and AP-1.

Authors+Show Affiliations

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. alice.wattel@sa.u-picardie.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15108355

Citation

Wattel, Alice, et al. "Flavonoid Quercetin Decreases Osteoclastic Differentiation Induced By RANKL Via a Mechanism Involving NF Kappa B and AP-1." Journal of Cellular Biochemistry, vol. 92, no. 2, 2004, pp. 285-95.
Wattel A, Kamel S, Prouillet C, et al. Flavonoid quercetin decreases osteoclastic differentiation induced by RANKL via a mechanism involving NF kappa B and AP-1. J Cell Biochem. 2004;92(2):285-95.
Wattel, A., Kamel, S., Prouillet, C., Petit, J. P., Lorget, F., Offord, E., & Brazier, M. (2004). Flavonoid quercetin decreases osteoclastic differentiation induced by RANKL via a mechanism involving NF kappa B and AP-1. Journal of Cellular Biochemistry, 92(2), 285-95.
Wattel A, et al. Flavonoid Quercetin Decreases Osteoclastic Differentiation Induced By RANKL Via a Mechanism Involving NF Kappa B and AP-1. J Cell Biochem. 2004 May 15;92(2):285-95. PubMed PMID: 15108355.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Flavonoid quercetin decreases osteoclastic differentiation induced by RANKL via a mechanism involving NF kappa B and AP-1. AU - Wattel,Alice, AU - Kamel,Said, AU - Prouillet,Christophe, AU - Petit,Jean-Pierre, AU - Lorget,Florence, AU - Offord,Elizabeth, AU - Brazier,Michel, PY - 2004/4/27/pubmed PY - 2005/1/15/medline PY - 2004/4/27/entrez SP - 285 EP - 95 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 92 IS - 2 N2 - 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 NF kappa B 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 microM) decreased osteoclastogenesis in a dose dependent manner in both models with significant effects observed at low concentrations, from 1 to 5 microM. The IC(50) value was about 1 microM. 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 (NF kappa B) and activator protein 1 (AP-1) activation. NF kappa B 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 NF kappa B and AP-1. SN - 0730-2312 UR - https://www.unboundmedicine.com/medline/citation/15108355/Flavonoid_quercetin_decreases_osteoclastic_differentiation_induced_by_RANKL_via_a_mechanism_involving_NF_kappa_B_and_AP_1_ L2 - https://doi.org/10.1002/jcb.20071 DB - PRIME DP - Unbound Medicine ER -