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http://dx.doi.org/10.14348/molcells.2014.0190

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)
Publication Information
Molecules and Cells / v.37, no.8, 2014 , pp. 628-635 More about this Journal
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.
Keywords
antiresorptive drugs; bone destruction; osteoclast; osteoclast maturation; (R)-TEMOSPho;
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