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Molecules and Cells

, Volume 32, Issue 5, pp 437–444 | Cite as

Simvastatin promotes osteogenic differentiation of mouse embryonic stem cells via canonical Wnt/β-catenin signaling

  • Ling Juan Qiao
  • Kyung Lhi Kang
  • Jung Sun Heo
Article

Abstract

Simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, has been known to reduce cholesterol biosynthesis. However, recent studies demonstrate that simvastatin shows diverse cholesterol-independent functions including cellular differentiation. In this study, we investigated the stimulatory effect of simvastatin on the osteogenic differentiation of mouse embryonic stem cells (ESCs). The osteogenic effect of simvastatin was observed at relatively low doses (ranging from 1 nM to 200 nM). Incubation of ESCs in simvastatin-supplemented osteogenic medium significantly increased alkaline phosphatase (ALP) activity at day 7. The matrix mineralization was also augmented and demonstrated pivotal levels after 14 days incubation of simvastatin. Osteogenic differentiation of ESCs by simvastatin was determined by upregulation of the mRNA expression of runtrelated gene 2 (Runx2), osterix (OSX), and osteocalcin (OCN) as osteogenic transcription factors. Moreover, the increased protein expression of OCN, osteopontin (OPN), and collagen type I (Coll I) was assessed using Western blot analysis and immunocytochemistry. However, the blockage of canonical Wnt signaling by DKK-1 downregulated simvastatin-induced ALP activity and the mRNA expression of each osteogenic transcription factor. Furthermore, the β-catenin specific siRNA transfection decreased the protein levels of OCN, OPN, and Coll I. Collectively, these findings suggest that simvastatin enhances the differentiation of ESCs toward osteogenic lineage through activation of canonical Wnt/β-catenin signaling.

Keywords

canonical Wnt/β-catenin signaling embryonic stem cells osteogenic differentiation simvastatin 

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Copyright information

© The Korean Society for Molecular and Cellular Biology and Springer Netherlands 2011

Authors and Affiliations

  • Ling Juan Qiao
    • 1
  • Kyung Lhi Kang
    • 2
  • Jung Sun Heo
    • 1
  1. 1.Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of DentistryKyung Hee UniversitySeoulKorea
  2. 2.Department of Periodontology, School of DentistryKyung Hee UniversitySeoulKorea

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