title: Flavonoids of Herba Epimedii stimulate osteogenic differentiation and suppress adipogenic differentiation of primary mesenchymal stem cells via estrogen receptor pathway.
abstract: BACKGROUND
  Accumulating evidence indicates that Herba Epimedii [Epimedii folium (Berberidaceae)] has anti-osteoporotic effect by stimulating osteoblastic bone formation and reducing osteoclastic bone resorption. However, the effect of Herba Epimedii in regulating the cross-talk between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) remains unclear.
  
  
  OBJECTIVE
  The present study investigates the effect of total flavonoids of Herba Epimedii (HETF) on the osteogenesis and adipogenesis of primary MSCs.
  
  
  METHODS
  HETF were prepared and identified by HPLC-fingerprinting, primary mouse MSCs in the presence of 0.006-6 μg/mL HETF for 2-10 d were subject to morphological, biochemical, and quantitative real-time PCR analysis.
  
  
  RESULTS
  Sixteen chemical components were identified in HETF by HPLC-fingerprinting and account for over 95% of the total area of HPLC peaks. During osteogenesis of MSCs, 0.006-6 μg/mL HETF promoted the proliferation of MSCs from 17% to 22%, increased alkaline phosphatase activity up to 3.7-fold (0.6 μg/mL), and extracellular calcium deposits from 1.2- to 1.4-folds by up-regulating the expression of runt-related transcription factor-2 (Runx-2) and bone morphogenetic protein-2 (BMP-2). Meanwhile, HETF suppressed the adipogenesis of MSCs by reducing the formation of adipocyte-like cells and accumulation of fat droplets by down-regulating the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ). The above biological activities of HETF were mainly through estrogen receptor-mediated pathway, which were blocked by estrogen receptor antagonist, ICI 182,780.
  
  
  CONCLUSIONS
  HETF could regulate Runx-2-mediated osteogenesis and PPAR-γ-mediated adipogenesis in MSCs and thus exhibit beneficial effects to bone health, which suggests a new strategy for treating patients with osteoporosis and obesity.
authors.affiliation: a School of Pharmacy, Guangdong Medical University , Dongguan , PR China .|b Guangdong Key Laboratory for Research and Development of Natural Drugs , Guangdong Medical College , Zhanjiang , PR China .|c Department of Biomedical Sciences , City University of Hong Kong , Kowloon Tong , Hong Kong , and.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: a School of Pharmacy, Guangdong Medical University , Dongguan , PR China .
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: a School of Pharmacy, Guangdong Medical University , Dongguan , PR China .
authors.forename: Zhenbin
authors.initials: Z
authors.lastname: Jia
authors.affiliation: d Department of Natural Products Chemistry , Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Yao
authors.affiliation: c Department of Biomedical Sciences , City University of Hong Kong , Kowloon Tong , Hong Kong , and.
authors.forename: Mengsu
authors.initials: M
authors.lastname: Yang
mesh_terms: D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D034181:Epimedium / Q000737:chemistry*; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D008815:Mice, Inbred Strains; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D010936:Plant Extracts / Q000737:chemistry; D061251:Primary Cell Culture; D060888:Real-Time Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D047495:PPAR gamma; D010936:Plant Extracts; D011960:Receptors, Estrogen
keywords: Adipogenesis; PPAR-γ; Runx-2; osteogenesis