Icariin promotes osteogenic differentiation of rat bone marrow stromal cells by activating the ERα-Wnt/β-catenin signaling pathway

Biomed Pharmacother. 2016 Dec:84:931-939. doi: 10.1016/j.biopha.2016.09.107. Epub 2016 Oct 17.

Abstract

Icariin, the main effective component of Herba Epimedii, has been identified to regulate the osteogenic differentiation of rat bone marrow stromal cells (rBMSCs) and have potential application in preventing bone loss and promoting bone regeneration. However, the underlying signaling pathway of its osteogenic effect remains unclear. Here, we investigated whether icariin could promote osteogenesis of rBMSCs through modulating the estrogen receptor alpha (ERα) and Wnt/β-catenin signaling pathways, which implicated in rBMSCs osteogenesis. rBMSCs were cultured in osteogenic induction medium and treated with icariin or together with ICI 182780 or DKK1, the effects on the expression of osteogenic genes and Wnt/β-catenin signaling were detected. Results indicated that icariin (0.1μM) markedly enhanced the proliferation of rBMSCs and alkaline phosphatase (ALP) activity. Additionally, icariin (0.1μM) significantly up-regulated the expression of osteogenic genes (Runx2, osteopotin, DLX5, osteocalcin, collagen type I, and ERα) and Wnt signal members (β-catenin, Lef1, TCF7, c-jun, c-myc, and cyclin D). Furthermore, icariin stimulated the activation of β-catenin as evidenced by increased total β-catenin protein and nuclear translocation. These osteogenesis-potentiating effects of icariin were blocked by ICI 182780 or DKK1. Taken together, these results suggest that the osteogenic effects of icariin on rBMSCs involves the ERα-Wnt/β-catenin signaling pathway.

Keywords: Bone marrow stromal cells; Icariin; Osteogenic differentiation; Wnt/β-catenin signaling.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Cells, Cultured
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / metabolism*
  • Flavonoids / pharmacology*
  • Fulvestrant
  • Gene Expression Regulation / drug effects
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Phenotype
  • Phosphorylation / drug effects
  • Protein Transport / drug effects
  • Rats, Sprague-Dawley
  • Wnt Signaling Pathway / drug effects*
  • Wnt Signaling Pathway / genetics
  • beta Catenin / metabolism

Substances

  • DKK1 protein, human
  • Estrogen Receptor alpha
  • Flavonoids
  • Intercellular Signaling Peptides and Proteins
  • beta Catenin
  • Fulvestrant
  • Estradiol
  • icariin