Silibinin inhibits osteoclast differentiation mediated by TNF family members

• Published in: Molecules and cells Vol. 28; no. 3; pp. 201 - 207
• Main Authors: Kim, Jung Ha, Kim, Kabsun, Jin, Hye Mi, Song, Insun, Youn, Bang Ung, Lee, Junwon, Kim, Nacksung
• Format: Journal Article
• Language: English
• Published: Springer Korean Society for Molecular and Cellular Biology 01.09.2009; 한국분자세포생물학회
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cell Biology; Cell Differentiation - drug effects; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors; Life Sciences; Macrophages - drug effects; Mice; NF-kappa B - antagonists & inhibitors; NFATC Transcription Factors - biosynthesis; Osteoclasts - cytology; Osteoclasts - drug effects; Osteoclasts - physiology; RANK Ligand - metabolism; RANK Ligand - pharmacology; Signal Transduction - drug effects; Silybin; Silymarin - pharmacology; Tumor Necrosis Factor-alpha - antagonists & inhibitors; 생물학; RANKL; osteoclast differentiation; gene regulation; TNF; Silibinin
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1007/s10059-009-0123-y

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.