Molecules and Cells

, Volume 28, Issue 3, pp 201–207 | Cite as

Silibinin inhibits osteoclast differentiation mediated by TNF family members

  • Jung Ha Kim
  • Kabsun Kim
  • Hye Mi Jin
  • Insun Song
  • Bang Ung Youn
  • Junwon Lee
  • Nacksung Kim
Article

Abstract

Silibinin is a polyphenolic flavonoid compound isolated from milk thistle (Silybum marianum), with known hepatoprotective, anticarcinogenic, and antioxidant effects. Herein, we show that silibinin inhibits receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis from RAW264.7 cells as well as from bone marrow-derived monocyte/macrophage cells in a dose-dependent manner. Silibinin has no effect on the expression of RANKL or the soluble RANKL decoy receptor osteoprotegerin (OPG) in osteoblasts. However, we demonstrate that silibinin can block the activation of NF-κB, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein (MAP) kinase, and extracellular signal-regulated kinase (ERK) in osteoclast precursors in response to RANKL. Furthermore, silibinin attenuates the induction of nuclear factor of activated T cells (NFAT) c1 and osteoclast-associated receptor (OSCAR) expression during RANKL-induced osteoclastogenesis. We demonstrate that silibinin can inhibit TNF-α-induced osteoclastogenesis as well as the expression of NFATc1 and OSCAR. Taken together, our results indicate that silibinin has the potential to inhibit osteoclast formation by attenuating the downstream signaling cascades associated with RANKL and TNF-α.

Keywords

gene regulation osteoclast differentiation RANKL Silibinin TNF 

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Copyright information

© The Korean Society for Molecular and Cellular Biology and Springer Netherlands 2009

Authors and Affiliations

  • Jung Ha Kim
    • 1
  • Kabsun Kim
    • 1
  • Hye Mi Jin
    • 1
  • Insun Song
    • 1
  • Bang Ung Youn
    • 1
  • Junwon Lee
    • 2
  • Nacksung Kim
    • 1
  1. 1.National Research Laboratory for Regulation of Bone Metabolism and Disease, Department of Pharmacology, Brain Korea 21Chonnam National University Medical SchoolGwangjuKorea
  2. 2.Department of Life Science and Genetic EngineeringPai Chai UniversityDaejeonKorea

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