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 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-kappaB 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.
Yonezawa
Takayuki
T
Research Institute for Biological Functions, Chubu University, 1200 Matsumoto, Kasugai-shi, Aichi 488-8501, Japan.
Hasegawa
Shin-Ichi
S
Ahn
Jae-Yong
JY
Cha
Byung-Yoon
BY
Teruya
Toshiaki
T
Hagiwara
Hiromi
H
Nagai
Kazuo
K
Woo
Je-Tae
JT
D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D008264:Macrophages; D051379:Mice; D009947:Organotin Compounds / Q000494:pharmacology*; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000502:physiology*; D047488:Retinoid X Receptors / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014220:Trialkyltin Compounds / Q000494:pharmacology*
D009947:Organotin Compounds; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014220:Trialkyltin Compounds; C011559:tributyltin; C030665:triphenyltin