title: Kaempferol as a flavonoid induces osteoblastic differentiation via estrogen receptor signaling.
abstract: BACKGROUND
  Flavonoids, a group of compounds mainly derived from vegetables and herbal medicines, chemically resemble estrogen and some have been used as estrogen substitutes. Kaempferol, a flavonol derived from the rhizome of Kaempferia galanga L., is a well-known phytoestrogen possessing osteogenic effects that is also found in a large number of plant foods.The herb K. galanga is a popular traditional aromatic medicinal plant that is widely used as food spice and in medicinal industries. In the present study, both the estrogenic and osteogenic properties of kaempferol are evaluated.
  
  
  METHODS
  Kaempferol was first evaluated for its estrogenic properties, including its effects on estrogen receptors. The osteogenic properties of kaempferol were further determined its induction effects on specific osteogenic enzymes and genes as well as the mineralization process in cultured rat osteoblasts.
  
  
  RESULTS
  Kaempferol activated the transcriptional activity of pERE-Luc (3.98 ± 0.31 folds at 50 μM) and induced estrogen receptor α (ERα) phosphorylation in cultured rat osteoblasts, and this ER activation was correlated with induction and associated with osteoblast differentiation biomarkers, including alkaline phosphatase activity and transcription of osteoblastic genes, e.g., type I collagen, osteonectin, osteocalcin, Runx2 and osterix. Kaempferol also promoted the mineralization process of osteoblasts (4.02 ± 0.41 folds at 50 μM). ER mediation of the kaempferol-induced effects was confirmed by pretreatment of the osteoblasts with an ER antagonist, ICI 182,780, which fully blocked the induction effect.
  
  
  CONCLUSIONS
  Our results showed that kaempferol stimulates osteogenic differentiation of cultured osteoblasts by acting through the estrogen receptor signaling.
authors.affiliation: Division of Life Science and Center for Chinese Medicine, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clearwater Bay, New Territories, Hong Kong SAR, China. botsim@ust.hk.
authors.forename: Ava Jiangyang
authors.initials: AJ
authors.lastname: Guo
authors.forename: Roy Chiyan
authors.initials: RC
authors.lastname: Choi
authors.forename: Ken Yuzhong
authors.initials: KY
authors.lastname: Zheng
authors.forename: Vicky Ping
authors.initials: VP
authors.lastname: Chen
authors.forename: Tina Tingxia
authors.initials: TT
authors.lastname: Dong
authors.forename: Zheng-Tao
authors.initials: ZT
authors.lastname: Wang
authors.forename: Günter
authors.initials: G
authors.lastname: Vollmer
authors.forename: David Taiwai
authors.initials: DT
authors.lastname: Lau
authors.forename: Karl Wah-Keung
authors.initials: KW
authors.lastname: Tsim