2-(trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate suppresses osteoclast maturation and bone resorption by targeting macrophage-colony stimulating factor signaling

So Jeong Park, Doo Ri Park, Deepak Bhattarai, Kyeong Lee, Jaesang Kim, Yun Soo Bae, Soo Young Lee

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Pages (from-to)628-635
Number of pages8
JournalMolecules and Cells
Volume37
Issue number8
DOIs
StatePublished - 19 Aug 2014

Keywords

  • (R)-TEMOSPho
  • Antiresorptive drugs
  • Bone destruction
  • Osteoclast
  • Osteoclast maturation

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