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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
- 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 S.J.; Park D.R.; Bhattarai D.; Lee K.; Kim J.; Bae Y.S.; Lee S.Y.
- Ewha Authors
- 배윤수; 이수영; 김재상
- SCOPUS Author ID
- 배윤수; 이수영; 김재상
- Issue Date
- Journal Title
- Molecules and Cells
- Molecules and Cells vol. 37, no. 8, pp. 628 - 635
- (R)-TEMOSPho; Antiresorptive drugs; Bone destruction; Osteoclast; Osteoclast maturation
- Korean Society for Molecular and Cellular Biology
- SCIE; SCOPUS; KCI
- Document Type
- 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.
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