title: Inhibitory effects of Stewartia koreana on osteoclast differentiation and bone resorption.
abstract: Osteoclasts are responsible for bone lysis in several bone diseases such as osteoporosis and rheumatoid arthritis. Natural products from plants have been invaluable source in discovery of compounds for new therapies. In this study, we screened plant products for potential application to therapy for bone loss using a primary osteoclastogenesis culture system and found that extract of Stewartia koreana (SKE) had a strong inhibitory effect on osteoclast formation. To gain molecular insights, we examined the effect of SKE on signaling pathways and transcription factors stimulated by the osteoclast differentiation factor RANKL. SKE suppressed the induction of c-Fos and NFATc1 by RANKL. However, SKE did not inhibit NF-kappaB activation by RANKL. Among the MAPKs stimulated by RANKL, SKE significantly reduced the activation of ERK and p38. Therefore, the anti-osteoclastogenic effect of SKE is likely to be elicited by interference with RANKL signaling to ERK and p38, which mediate the induction of c-Fos and subsequently that of NFATc1. Consistent with the in vitro effect on osteoclast differentiation, SKE showed a great inhibitory effect on in vivo bone loss in LPS-challenged mice. Taken together, we demonstrated that SKE has inhibitory effects on osteoclast differentiation in vitro and confirmed its in vivo efficacy in prevention of inflammatory bone loss.
authors.affiliation: Department of Cell and Developmental Biology, BK21 Program, Dental Research Institute, Seoul National University School of Dentistry, 28 Yeongon-Dong, Chongno-Gu, Seoul, 110-749, South Korea.
authors.forename: Cheol Kyu
authors.initials: CK
authors.lastname: Park
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Han Bok
authors.initials: HB
authors.lastname: Kwak
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Lee
authors.forename: Myun-Ho
authors.initials: MH
authors.lastname: Bang
authors.forename: Chul Min
authors.initials: CM
authors.lastname: Kim
authors.forename: Youngkyun
authors.initials: Y
authors.lastname: Lee
authors.forename: Dae Kyun
authors.initials: DK
authors.lastname: Chung
authors.forename: Nam-In
authors.initials: NI
authors.lastname: Baek
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Zang Hee
authors.initials: ZH
authors.lastname: Lee
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D001862:Bone Resorption / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D053245:RANK Ligand / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D028242:Theaceae / Q000737:chemistry*
chemical_list: D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D020928:Mitogen-Activated Protein Kinases