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Inhibitory effect of luteolin on osteoclast differentiation and function

Title
Inhibitory effect of luteolin on osteoclast differentiation and function
Authors
Lee, Ji-WonAhn, Jae-YongHasegawa, Shin-ichiCha, Byung-YoonYonezawa, TakayukiNagai, KazuoSeo, Hwa-JeongJeon, Won BaeWoo, Je-Tae
DGIST Authors
Jeon, Won Bae
Issue Date
2009-12
Citation
Cytotechnology, 61(3), 125-134
Type
Article
Article Type
Article
Keywords
Tumor-Necrosis-FactorNf-Kappa-BActivated Protein-KinaseGene-ExpressionBone-ResorptionC-JunSignal-TransductionReceptor ActivatorNuclear-FactorFlavonoids
ISSN
0920-9069
Abstract
Osteoclasts are multinucleated cells that play a crucial role in bone resorption, and are formed by the fusion of mononuclear osteoclasts derived from osteoclast precursors of the macrophage lineage. Compounds that specifically target functional osteoclasts would be ideal candidates for anti-resorptive agents for clinical applications. In the present study, we investigated the effects of luteolin, a flavonoid, on the regulation of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, functions and signaling pathway. Addition of luteolin to a coculture system of mouse bone marrow cells and ST2 cells in the presence of 10-8 M 1α,25(OH)2D3 caused significant inhibition of osteoclastogenesis. Luteolin had no effects on the 1α,25(OH) 2D3-induced expressions of RANKL, osteoprotegerin and macrophage colony-stimulating factor mRNAs. Next, we examined the direct effects of luteolin on osteoclast precursors using bone marrow macrophages and RAW264.7 cells. Luteolin completely inhibited RANKL-induced osteoclast formation. Moreover, luteolin inhibited the bone resorption by mature osteoclasts accompanied by the disruption of their actin rings, and these effects were reversely induced by the disruption of the actin rings in mature osteoclasts. Finally, we found that luteolin inhibited RANKL-induced osteoclastogenesis through the suppression of ATF2, downstream of p38 MAPK and nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) expression, respectively. Taken together, the present results indicate that naturally occurring luteolin has inhibitory activities toward both osteoclast differentiation and functions through inhibition of RANKL-induced signaling pathway as well as actin ring disruption, respectively. © 2010 Springer Science+Business Media B.V.
URI
http://hdl.handle.net/20.500.11750/6508
DOI
10.1007/s10616-010-9253-5
Publisher
Springer
Related Researcher
Files:
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Collection:
Companion Diagnostics and Medical Technology Research Group1. Journal Articles


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