Furosin, an ellagitannin, suppresses RANKL-induced osteoclast differentiation and function through inhibition of MAP kinase activation and actin ring formation.
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.
Park
Eui Kyun
EK
Skeletal Diseases Genomic Research Center, Kyungpook National University Hospital, Kyungpook National University, Daegu 700-412, Republic of Korea.
Kim
Myung Sunny
MS
Lee
Seung Ho
SH
Kim
Kyung Hee
KH
Park
Ju-Young
JY
Kim
Tae-Ho
TH
Lee
In-Seon
IS
Woo
Je-Tae
JT
Jung
Jae-Chang
JC
Shin
Hong-In
HI
Choi
Je-Yong
JY
Kim
Shin-Yoon
SY
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
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