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Safflower Seed Extract Inhibits Osteoclast Differentiation by Suppression of the p38 Mitogen‐activated Protein Kinase and IκB Kinase Activity
Author(s) -
Moon HoJin,
Kim EunKyung,
Nam Yun Sik,
Kim Jung Ho,
Ko WanKyu,
Lee JinMoo,
Lee ChangHoon,
Jang JunBock,
Lee KyungSub,
Kwon Il Keun
Publication year - 2012
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.4622
Subject(s) - rankl , osteoclast , p38 mitogen activated protein kinases , protein kinase a , activator (genetics) , multinucleate , microbiology and biotechnology , kinase , chemistry , cellular differentiation , bone resorption , biology , biochemistry , receptor , endocrinology , gene
Safflower seed has been reported to have a protective effect against bone loss diseases. However, the precise molecular mechanisms underlying the inhibitory effect of safflower seed in osteoclast differentiation remain unclear. In this study, we investigated the inhibitory action of safflower seed extract (SSE) on the receptor activator of nuclear factor κB ligand (RANKL)‐induced osteoclastogenesis in cultured mouse‐derived bone marrow macrophages (BMMs). We found that SSE significantly inhibited the formation of tartrate‐resistant acid phosphatase (TRAP)‐positive multinucleated cells in BMMs without cytotoxicity. The gene expressions of nuclear factor of activated T‐cells (NFATc1) and TRAP, which are genetic markers of osteoclast differentiation, were substantially decreased by SSE in a dose‐dependent manner. Also, SSE diminished RANKL‐mediated intracellular reactive oxygen species (ROS) generation on osteoclastogenesis in a dose‐dependent manner. The SSE thereafter suppressed RANKL‐induced p38 mitogen‐activated protein kinase and IκBα kinase signalling activities which were activated by ROS generation for osteoclastogenesis. Additionally, SSE was found to decrease RANKL‐induced actin ring formation, which is required for bone resorption activity. Taken together, our results suggest that SSE acts as a RANKL‐induced osteoclastogenesis inhibitor by suppression of ROS generation. This induces a remarkable suppression of the p38 and IκBα kinase pathways, thereby suppressing the gene expression of NFATc1 in osteoclast precursors. Copyright © 2012 John Wiley & Sons, Ltd.