, Volume 61, Issue 3, pp 125–134 | Cite as

Inhibitory effect of luteolin on osteoclast differentiation and function

  • Ji-Won Lee
  • Jae-Yong Ahn
  • Shin-ichi Hasegawa
  • Byung-Yoon Cha
  • Takayuki Yonezawa
  • Kazuo Nagai
  • Hwa-Jeong Seo
  • Won-Bae Jeon
  • Je-Tae WooEmail author
Original Research


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.


Luteolin RANKL Osteoclast ATF2 NFATc1 



This study was supported by an endowment from Erina Co. Inc. and partially funded by a grant for Biodefense Programs of the Ministry of Education, Science and Technology of the Republic of Korea.


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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Ji-Won Lee
    • 1
  • Jae-Yong Ahn
    • 1
  • Shin-ichi Hasegawa
    • 1
  • Byung-Yoon Cha
    • 1
  • Takayuki Yonezawa
    • 1
  • Kazuo Nagai
    • 1
  • Hwa-Jeong Seo
    • 2
  • Won-Bae Jeon
    • 2
  • Je-Tae Woo
    • 1
    • 3
    Email author
  1. 1.Department of Biological ChemistryChubu UniversityKasugaiJapan
  2. 2.Daegu Gyoengbuk Institute of Science and TechnologyDaeguKorea
  3. 3.Research and Development DepartmentErina Co., Inc.TokyoJapan

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