title: Inhibition of osteoclastogenic differentiation by Ikarisoside A in RAW 264.7 cells via JNK and NF-kappaB signaling pathways.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hwa Jung
authors.initials: HJ
authors.lastname: Choi
authors.forename: Young Ran
authors.initials: YR
authors.lastname: Park
authors.forename: Manoj
authors.initials: M
authors.lastname: Nepal
authors.forename: Bo-Yun
authors.initials: BY
authors.lastname: Choi
authors.forename: Nam-Pyo
authors.initials: NP
authors.lastname: Cho
authors.forename: Seoung Hwan
authors.initials: SH
authors.lastname: Choi
authors.forename: Soo Rye
authors.initials: SR
authors.lastname: Heo
authors.forename: Hyung Sup
authors.initials: HS
authors.lastname: Kim
authors.forename: Moon-Sik
authors.initials: MS
authors.lastname: Yang
authors.forename: Yunjo
authors.initials: Y
authors.lastname: Soh
mesh_terms: 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
chemical_list: 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