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The flavonoid fisetin promotes osteoblasts differentiation through Runx2 transcriptional activity

Authors

  • Laurent Léotoing,

    1. INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France
    2. Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France
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  • Marie-Jeanne Davicco,

    1. INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France
    2. Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France
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  • Patrice Lebecque,

    1. INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France
    2. Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France
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  • Yohann Wittrant,

    Corresponding author
    1. INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France
    2. Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France
    • Correspondence: Dr. Yohann Wittrant, UMR1019 INRA, Université d'Auvergne, Unité de Nutrition Humaine, 63122 Saint Genès Champanelle, France

      E-mail: yohann.wittrant@clermont.inra.fr

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  • Véronique Coxam

    1. INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France
    2. Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France
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Abstract

Scope

Flavonoids represent a group of polyphenolic compounds commonly found in daily nutrition with proven health benefits. Among this group, the flavonol fisetin has been previously shown to protect bone by repressing osteoclast differentiation. In the present study, we investigated the role of fisetin in regulating osteoblasts physiology.

Methods and results

In vivo mice treated with LPSs exhibited osteoporosis features associated with a dramatic repression of osteoblast marker expression. In this model, inhibition of osteocalcin and type I collagen alpha 1 transcription was partially countered by a daily consumption of fisetin. Interestingly, in vitro, fisetin promoted both osteoblast alkaline phosphatase activity and mineralization process. To decipher how fisetin may exert its positive effect on osteoblastogenesis, we analyzed its ability to control the runt-related transcription factor 2 (Runx2), a key organizer in developing and maturing osteoblasts. While fisetin did not impact Runx2 mRNA and protein levels, it upregulated its transcriptional activity. Actually, fisetin stimulated the luciferase activity of a reporter plasmid driven by the osteocalcin gene promoter that contains Runx2 binding sites and promoted the mRNA expression of osteocalcin and type I collagen alpha 1 targets.

Conclusion

Bone sparing properties of fisetin also rely on its positive influence on osteoblast differentiation and activity.

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