Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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2-(Trimethylammonium) Ethyl (R)-3-Methoxy-3-oxo-2-Stearamidopropyl Phosphate Suppresses Osteoclast Maturation and Bone Resorption by Targeting Macrophage-Colony Stimulating Factor Signaling

  • Park, So Jeong (Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University) ;
  • Park, Doo Ri (Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University) ;
  • Bhattarai, Deepak (BK21 Plus R-FIND Team, College of Pharmacy, Dongguk University) ;
  • Lee, Kyeong (BK21 Plus R-FIND Team, College of Pharmacy, Dongguk University) ;
  • Kim, Jaesang (Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University) ;
  • Bae, Yun Soo (Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University) ;
  • Lee, Soo Young (Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University)
  • Received : 2014.07.03
  • Accepted : 2014.07.28
  • Published : 2014.08.31
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Abstract

2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.

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