Inhibition of osteoclastogenic differentiation by Ikarisoside A in RAW 264.7 cells via JNK and NF-kappaB signaling pathways

Eur J Pharmacol. 2010 Jun 25;636(1-3):28-35. doi: 10.1016/j.ejphar.2010.03.023. Epub 2010 Mar 29.


Osteoclasts are specialized bone-resorbing cells derived from multipotent myeloid progenitor cells. They play a crucial homeostatic role in skeletal modeling and remodeling and destroy bone in many pathologic conditions. Receptor activator of NF-kappaB ligand (RANKL) is essential to osteoclastogenesis. In this study, we investigated the effects of Ikarisoside A, isolated from Epimedium koreanum (Berberidaceae), on osteoclastogenesis in RANKL-treated murine monocyte/macrophage RAW 264.7 cells. The results indicate that Ikarisoside A is a potent inhibitor of osteoclastogenesis in RANKL-stimulated RAW 264.7 cells as well as in bone marrow-derived macrophages. The inhibitory effect of Ikarisoside A resulted in decrease of osteoclast-specific genes like matrix metalloproteinase 9 (MMP9), tartrate-resistant acid phosphatase (TRAP), receptor activator of NF-kappaB (RANK), and cathepsin K. Moreover, Ikarisoside A blocked the resorbing capacity of RAW 264.7 cells on calcium phosphate-coated plates. Ikarisoside A also has inhibitory effects on the RANKL-mediated activation of NF-kappaB, JNK, and Akt. Finally, Ikarisoside A clearly decreased the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1) as well as the transcriptional activity of NFATc1, the master regulator of osteoclast differentiation. The data indicate that Ikarisoside A has potential for use in treatment of diseases involving abnormal bone lysis such as osteoporosis, rheumatoid arthritis, and periodontal bone erosion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Resorption / metabolism
  • Cell Differentiation / drug effects*
  • Cell Line
  • Enzyme Activation / drug effects
  • Flavonoids / pharmacology*
  • Gene Expression Regulation / drug effects
  • Glycosides / pharmacology*
  • MAP Kinase Kinase 4 / metabolism*
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • NF-kappa B / metabolism*
  • NFATC Transcription Factors / metabolism
  • Osteoclasts / cytology*
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • Proto-Oncogene Proteins c-fos / genetics
  • RANK Ligand / pharmacology


  • Flavonoids
  • Glycosides
  • Ikarisoside A
  • NF-kappa B
  • NFATC Transcription Factors
  • Proto-Oncogene Proteins c-fos
  • RANK Ligand
  • MAP Kinase Kinase 4