title: Stimulatory effect of naturally occurring flavonols quercetin and kaempferol on alkaline phosphatase activity in MG-63 human osteoblasts through ERK and estrogen receptor pathway.
abstract: Many plant-derived substances have estrogenic activities. Due to their ability to bind the estrogen receptor (ER), these compounds have the potential to counteract the deleterious effects of estrogen deficiency on bone. In this study, we investigated the in vitro effect of two widespread flavonols, quercetin and kaempferol, on alkaline phosphatase (ALP) activity in MG-63 cultured human osteoblasts. We found that both flavonols significantly increased ALP activity. This effect was markedly reduced by PD 98059, an inhibitor of the extracellular regulated kinase (ERK) pathway, and by ICI 182780, an antagonist of ERs. Western blot studies confirmed that ERK is rapidly activated in cells treated by both flavonols. Finally, ICI 182780 markedly inhibits the flavonol-induced ERK activation. The data presented in this study support the conclusion that, in MG-63 osteoblasts (i) the increase in ALP activity by flavonols involves a rapid stimulation of ERK activation but also involves the ER, and that (ii) the activation of ERK by flavonols occurs most likely downstream of the ERs activation. Taken together, these results suggest that flavonols derivatives as quercetin and kaempferol can stimulate osteoblastic activity. Such compounds may represent new pharmacological tools for the treatment of osteoporosis.
authors.affiliation: Laboratoire de Biochimie, JE 23 29, CHRU d'Amiens, Hôpital Nord, 80054 Amiens Cedex 01, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Prouillet
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Mazière
authors.forename: Cécile
authors.initials: C
authors.lastname: Mazière
authors.forename: Alice
authors.initials: A
authors.lastname: Wattel
authors.forename: Michel
authors.initials: M
authors.lastname: Brazier
authors.forename: Saïd
authors.initials: S
authors.lastname: Kamel
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects*; D011794:Quercetin / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005419:Flavonoids; D044949:Kaempferols; D011960:Receptors, Estrogen; D004958:Estradiol; D004815:Epidermal Growth Factor; C006552:kaempferol; D011794:Quercetin; D020928:Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one