Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 443, Issue 2, Pages 658-665Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2013.12.029
Keywords
Dioscin; Osteoclast; Osteolysis; AKT cascades
Categories
Funding
- Program for Innovative Research Team of Shanghai Municipal Education Commission (Phase I)
- Shanghai Municipal Education Commission [13YZ031]
- Key Disciplines of Shanghai Municipal Education Commission of China [J50206]
- National Natural Science Foundation for the Youth of China [81201364]
- Scientific Research Foundation for Returned Overseas Chinese Scholars from the State Human Resource Ministry
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Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-kappa B) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases. (C) 2013 Elsevier Inc. All rights reserved.
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