Silibinin Inhibits Osteoclast Differentiation Mediated by TNF Family Members

다국어 초록 (Multilingual Abstract)

Silibinin is a polyphenolic flavonoid compound isolated
from milk thistle (páäóÄìã=ã~êá~åìã), 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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