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Silibinin inhibits osteoclast differentiation mediated by TNF family members

  • Published:
Molecules and Cells

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.

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Authors and Affiliations

  1. National Research Laboratory for Regulation of Bone Metabolism and Disease, Department of Pharmacology, Brain Korea 21, Chonnam National University Medical School, Gwangju, 501-746, Korea

    Jung Ha Kim, Kabsun Kim, Hye Mi Jin, Insun Song, Bang Ung Youn & Nacksung Kim

  2. Department of Life Science and Genetic Engineering, Pai Chai University, Daejeon, 302-735, Korea

    Junwon Lee

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  1. Jung Ha Kim
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  2. Kabsun Kim
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  3. Hye Mi Jin
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  4. Insun Song
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  5. Bang Ung Youn
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  6. Junwon Lee
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  7. Nacksung Kim
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Correspondence to Nacksung Kim.

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Kim, J.H., Kim, K., Jin, H.M. et al. Silibinin inhibits osteoclast differentiation mediated by TNF family members. Mol Cells 28, 201–207 (2009). https://doi.org/10.1007/s10059-009-0123-y

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  • DOI: https://doi.org/10.1007/s10059-009-0123-y

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