Silibinin inhibits osteoclast differentiation mediated by TNF family members.
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.
Kim
Jung Ha
JH
National Research Laboratory for Regulation of Bone Metabolism and Disease, Department of Pharmacology, Brain Korea 21, Chonnam National University Medical School, Gwangju, Korea.
Kim
Kabsun
K
Jin
Hye Mi
HM
Song
Insun
I
Youn
Bang Ung
BU
Lee
Junwon
J
Kim
Nacksung
N
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D050778:NFATC Transcription Factors / Q000096:biosynthesis; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D053245:RANK Ligand / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D016328:NF-kappa B; D050778:NFATC Transcription Factors; D053245:RANK Ligand; D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D000077385:Silybin; D048031:JNK Mitogen-Activated Protein Kinases