期刊
MOLECULES AND CELLS
卷 37, 期 8, 页码 628-635出版社
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
DOI: 10.14348/molcells.2014.0190
关键词
antiresorptive drugs; bone destruction; osteoclast; osteoclast maturation; (R)-TEMOSPho
资金
- National Research Foundation of Korea (NRF) grant - Korea Government (MSIP) [2013R1A2A1A05005153, 2012R1A5A10 48236, 2012M3A9C5048708]
- National Research Foundation of Korea [2012M3A9C5048708, 2013R1A2A1A05005153] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
2-(Trimethylammonium) ethyl (R)/3-methoxy-3-oxo-2-steara-midopropyl 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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