title: Furosin, an ellagitannin, suppresses RANKL-induced osteoclast differentiation and function through inhibition of MAP kinase activation and actin ring formation.
abstract: Phenolic compounds including tannins and flavonoids have been implicated in suppression of osteoclast differentiation/function and prevention of bone diseases. However, the effects of hydrolysable tannins on bone metabolism remain to be elucidated. In this study, we found that furosin, a hydrolysable tannin, markedly decreased the differentiation of both murine bone marrow mononuclear cells and Raw264.7 cells into osteoclasts, as revealed by the reduced number of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells and decreased TRAP activity. Furosin appears to target at the early stage of osteoclastic differentiation while having no cytotoxic effect on osteoclast precursors. Analysis of the inhibitory mechanisms of furosin revealed that it inhibited the receptor activator of nuclear factor-kappaB ligand (RANKL)-induced activation of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK)/activating protein-1 (AP-1). Furthermore, furosin reduced resorption pit formation in osteoclasts, which was accompanied by disruption of the actin rings. Taken together, these results demonstrate that naturally occurring furosin has an inhibitory activity on both osteoclast differentiation and function through mechanisms involving inhibition of the RANKL-induced p38MAPK and JNK/AP-1 activation as well as actin ring formation.
authors.affiliation: Skeletal Diseases Genomic Research Center, Kyungpook National University Hospital, Kyungpook National University, Daegu 700-412, Republic of Korea.
authors.forename: Eui Kyun
authors.initials: EK
authors.lastname: Park
authors.forename: Myung Sunny
authors.initials: MS
authors.lastname: Kim
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Kim
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Kim
authors.forename: In-Seon
authors.initials: IS
authors.lastname: Lee
authors.forename: Je-Tae
authors.initials: JT
authors.lastname: Woo
authors.forename: Jae-Chang
authors.initials: JC
authors.lastname: Jung
authors.forename: Hong-In
authors.initials: HI
authors.lastname: Shin
authors.forename: Je-Yong
authors.initials: JY
authors.lastname: Choi
authors.forename: Shin-Yoon
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D011487:Protein Conformation; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B
chemical_list: D000199:Actins; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D047348:Hydrolyzable Tannins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; C099795:furosin; D020928:Mitogen-Activated Protein Kinases