Tributyltin and triphenyltin inhibit osteoclast differentiation through a retinoic acid receptor-dependent signaling pathway

Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), have been widely used in agriculture and industry. Although these compounds are known to have many toxic effects, including endocrine-disrupting effects, their effects on bone resorption are unknown. In this study, we investigate...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2007-03, Vol.355 (1), p.10-15
Main Authors: Yonezawa, Takayuki, Hasegawa, Shin-ichi, Ahn, Jae-Yong, Cha, Byung-Yoon, Teruya, Toshiaki, Hagiwara, Hiromi, Nagai, Kazuo, Woo, Je-Tae
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
AGRICULTURE
Animals
Bone resorption
Bone Resorption - physiopathology
Cell Differentiation - drug effects
Cell Line
Cell Survival - drug effects
INHIBITION
LIGANDS
Macrophages
MICE
ORGANOMETALLIC COMPOUNDS
Organotin compound
Organotin Compounds - pharmacology
Osteoclast
Osteoclasts - cytology
Osteoclasts - drug effects
RECEPTORS
Receptors, Retinoic Acid - antagonists & inhibitors
Receptors, Retinoic Acid - physiology
RETINOIC ACID
Retinoid X Receptors - drug effects
Retinoid X Receptors - physiology
Signal Transduction - drug effects
Signal Transduction - physiology
SKELETON
TIN COMPOUNDS
TOXICITY
Trialkyltin Compounds - pharmacology
Tributyltin
Triphenyltin
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), have been widely used in agriculture and industry. Although these compounds are known to have many toxic effects, including endocrine-disrupting effects, their effects on bone resorption are unknown. In this study, we investigated the effects of organotin compounds, such as monobutyltin (MBT), dibutyltin (DBT), TBT, and TPT, on osteoclast differentiation using mouse monocytic RAW264.7 cells. MBT and DBT had no effects, whereas TBT and TPT dose-dependently inhibited osteoclast differentiation at concentrations of 3–30 nM. Treatment with a retinoic acid receptor (RAR)-specific antagonist, Ro41-5253, restored the inhibition of osteoclastogenesis by TBT and TPT. TBT and TPT reduced receptor activator of nuclear factor-κB ligand (RANKL) induced nuclear factor of activated T cells (NFAT) c1 expression, and the reduction in NFATc1 expression was recovered by Ro41-5253. Our results suggest that TBT and TPT suppress osteoclastogenesis by inhibiting RANKL-induced NFATc1 expression via an RAR-dependent signaling pathway.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2006.12.237