title: The flavonoid fisetin promotes osteoblasts differentiation through Runx2 transcriptional activity.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Bone sparing properties of fisetin also rely on its positive influence on osteoblast differentiation and activity.
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Léotoing
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Davicco
authors.forename: Patrice
authors.initials: P
authors.lastname: Lebecque
authors.forename: Yohann
authors.initials: Y
authors.lastname: Wittrant
authors.forename: Véronique
authors.initials: V
authors.lastname: Coxam
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D008070:Lipopolysaccharides / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit; D005419:Flavonoids; D044948:Flavonols; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C493717:Runx2 protein, rat; D014157:Transcription Factors; D015675:Osteocalcin; C017875:fisetin
keywords: Bone; Fisetin; Osteoblast; Polyphenol; Runx2