Inhibitory effect of (-)-saucerneol on osteoclast differentiation and bone pit formation.
In this study, the effect of (-)-saucerneol, one of the lignans isolated from Saururus chinensis, on osteoclast differentiation and bone resorption was evaluated in two in vitro models for osteoclast differentiation, the receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL)-treated RAW264.7 cells and mouse BMMs treated with both RANKL and macrophage-colony stimulating factor. (-)-Saucerneol significantly inhibited the RANKL-induced activity of tartrate-resistance acid phosphatase (TRAP, an early marker of osteoclast formation) and formation of osteoclasts in a dose-dependent manner. Interestingly, (-)-saucerneol was shown to inhibit the RANKL-induced activation of extracellular signal-regulated kinase in both in vitro models. In addition, (-)-saucerneol inhibited the bone resorptive activity and the expression of transcription factors and genes essential for osteoclast formation and bone resorption as well. In conclusion, (-)-saucerneol has a potential to inhibit the osteoclast differentiation via preventing the activation of ERK signaling pathway. In addition, its activity to inhibit the bone resorption activities of osteoclasts could result from its potential to inhibit RANKL-induced expression levels of transcription factors and genes essential for bone resorption.
Kim
Soon Nam
SN
Laboratory of Chemical Genomics, Korea Research Institute of Chemical Technology, Daejeon 305-600, Korea.
Kim
Myung Hee
MH
Kim
Young Sup
YS
Ryu
Shi Yong
SY
Min
Yong Ki
YK
Kim
Seong Hwan
SH
D000135:Acid Phosphatase / Q000037:antagonists & inhibitors; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D002460:Cell Line; D005663:Furans / Q000302:isolation & purification / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects*; D053245:RANK Ligand / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism
D005663:Furans; D017705:Lignans; D053245:RANK Ligand; D014157:Transcription Factors; D016173:Macrophage Colony-Stimulating Factor; D020928:Mitogen-Activated Protein Kinases; D000135:Acid Phosphatase