title: Safflower seed extract inhibits osteoclast differentiation by suppression of the p38 mitogen-activated protein kinase and IκB kinase activity.
abstract: 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.
authors.affiliation: Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Ho-Jin
authors.initials: HJ
authors.lastname: Moon
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Yun Sik
authors.initials: YS
authors.lastname: Nam
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Wan-Kyu
authors.initials: WK
authors.lastname: Ko
authors.forename: Jin-Moo
authors.initials: JM
authors.lastname: Lee
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Lee
authors.forename: Jun-Bock
authors.initials: JB
authors.lastname: Jang
authors.forename: Kyung-Sub
authors.initials: KS
authors.lastname: Lee
authors.forename: Il Keun
authors.initials: IK
authors.lastname: Kwon
mesh_terms: D000818:Animals; D031187:Carthamus tinctorius / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D005227:Fatty Acids / Q000737:chemistry; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012639:Seeds / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D010936:Plant Extracts; D053245:RANK Ligand; D017382:Reactive Oxygen Species; C505689:Tnfsf11 protein, mouse; D051550:I-kappa B Kinase; D048051:p38 Mitogen-Activated Protein Kinases