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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

Title
2-(trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate suppresses osteoclast maturation and bone resorption by targeting macrophage-colony stimulating factor signaling
Authors
Park S.J.Park D.R.Bhattarai D.Lee K.Kim J.Bae Y.S.Lee S.Y.
Ewha Authors
배윤수이수영김재상
SCOPUS Author ID
배윤수scopus; 이수영scopus; 김재상scopus
Issue Date
2014
Journal Title
Molecules and Cells
ISSN
1016-8478JCR Link
Citation
vol. 37, no. 8, pp. 628 - 635
Keywords
(R)-TEMOSPhoAntiresorptive drugsBone destructionOsteoclastOsteoclast maturation
Publisher
Korean Society for Molecular and Cellular Biology
Indexed
SCI; SCIE; SCOPUS; KCI WOS scopus
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 pro-genitor 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 macro-phage-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. © The Korean Society for Molecular and Cellular Biology. All rights reserved.
DOI
10.14348/molcells.2014.0190
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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