Inhibition of osteoclastogenic differentiation by Ikarisoside A in RAW 264.7 cells via JNK and NF-kappaB signaling pathways.
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.
Choi
Hwa Jung
HJ
Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 project, Chonbuk National University, Jeon-Ju 561-756, Republic of Korea.
Park
Young Ran
YR
Nepal
Manoj
M
Choi
Bo-Yun
BY
Cho
Nam-Pyo
NP
Choi
Seoung Hwan
SH
Heo
Soo Rye
SR
Kim
Hyung Sup
HS
Yang
Moon-Sik
MS
Soh
Yunjo
Y
D000818:Animals; D001862:Bone Resorption / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006027:Glycosides / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D053245:RANK Ligand / Q000494:pharmacology
D005419:Flavonoids; D006027:Glycosides; C538782:Ikarisoside A; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D048670:MAP Kinase Kinase 4