The Effect of Quercetin on the Osteogenesic Differentiation and Angiogenic Factor Expression of Bone Marrow-Derived Mesenchymal Stem Cells

PLoS One. 2015 Jun 8;10(6):e0129605. doi: 10.1371/journal.pone.0129605. eCollection 2015.

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) are widely used in regenerative medicine in light of their ability to differentiate along the chondrogenic and osteogenic lineages. As a type of traditional Chinese medicine, quercetin has been preliminarily reported to promote osteogenic differentiation in osteoblasts. In the present study, the effects of quercetin on the proliferation, viability, cellular morphology, osteogenic differentiation and angiogenic factor secretion of rat BMSCs (rBMSCs) were examined by MTT assay, fluorescence activated cell sorter (FACS) analysis, real-time quantitative PCR (RT-PCR) analysis, alkaline phosphatase (ALP) activity and calcium deposition assays, and Enzyme-linked immunosorbent assay (ELISA). Moreover, whether mitogen-activated protein kinase (MAPK) signaling pathways were involved in these processes was also explored. The results showed that quercetin significantly enhanced the cell proliferation, osteogenic differentiation and angiogenic factor secretion of rBMSCs in a dose-dependent manner, with a concentration of 2 μM achieving the greatest stimulatory effect. Moreover, the activation of the extracellular signal-regulated protein kinases (ERK) and p38 pathways was observed in quercetin-treated rBMSCs. Furthermore, these induction effects could be repressed by either the ERK inhibitor PD98059 or the p38 inhibitor SB202190, respectively. These data indicated that quercetin could promote the proliferation, osteogenic differentiation and angiogenic factor secretion of rBMSCs in vitro, partially through the ERK and p38 signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Angiogenesis Inducing Agents / metabolism*
  • Animals
  • Antioxidants / pharmacology*
  • Calcium / metabolism
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Cell Survival / drug effects
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism*
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / genetics
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Protein Kinase Inhibitors / pharmacology
  • Quercetin / pharmacology*
  • Rats
  • Signal Transduction / drug effects
  • Vascular Endothelial Growth Factor A / metabolism
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Angiogenesis Inducing Agents
  • Antioxidants
  • Protein Kinase Inhibitors
  • Vascular Endothelial Growth Factor A
  • Quercetin
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Alkaline Phosphatase
  • Calcium

Grants and funding

This work was funded by National Natural Science Foundation of China (81171458, 81470713 and 81400554), Specialized Research Fund for the Doctoral Program of Higher Education (20110073110076), Science and Technology Committee of Shanghai Municipality (14140904100, 14YF1402400 and 12nm0501600), Medicine and Engineering Cross Project of Shanghai Jiao Tong University (YG2012SM29).