Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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A Receptor Tyrosine Kinase Inhibitor, Dovitinib (TKI-258), Enhances BMP-2-Induced Osteoblast Differentiation In Vitro

  • Lee, Yura (Department of Biomedical Laboratory Science, School of Medicine, Eulji University) ;
  • Bae, Kyoung Jun (Department of Biomedical Laboratory Science, School of Medicine, Eulji University) ;
  • Chon, Hae Jung (Department of Biomedical Laboratory Science, School of Medicine, Eulji University) ;
  • Kim, Seong Hwan (Laboratory of Translational Therapeutics, Korea Research Institute of Chemical Technology) ;
  • Kim, Soon Ae (Department of Pharmacology, School of Medicine, Eulji University) ;
  • Kim, Jiyeon (Department of Biomedical Laboratory Science, School of Medicine, Eulji University)
  • Received : 2015.10.27
  • Accepted : 2016.02.25
  • Published : 2016.05.31
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Abstract

Dovitinib (TKI258) is a small molecule multi-kinase inhibitor currently in clinical phase I/II/III development for the treatment of various types of cancers. This drug has a safe and effective pharmacokinetic/pharmacodynamic profile. Although dovitinib can bind several kinases at nanomolar concentrations, there are no reports relating to osteoporosis or osteoblast differentiation. Herein, we investigated the effect of dovitinib on human recombinant bone morphogenetic protein (BMP)-2-induced osteoblast differentiation in a cell culture model. Dovitinib enhanced the BMP-2-induced alkaline phosphatase (ALP) induction, which is a representative marker of osteoblast differentiation. Dovitinib also stimulated the translocation of phosphorylated Smad1/5/8 into the nucleus and phosphorylation of mitogen-activated protein kinases, including ERK1/2 and p38. In addition, the mRNA expression of BMP-4, BMP-7, ALP, and OCN increased with dovitinib treatment. Our results suggest that dovitinib has a potent stimulating effect on BMP-2-induced osteoblast differentiation and this existing drug has potential for repositioning in the treatment of bone-related disorders.

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References

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