Tributyltin and triphenyltin inhibit osteoclast differentiation through a retinoic acid receptor-dependent signaling pathway.
Tributyltin and triphenyltin inhibit osteoclast differentiation through a retinoic acid receptor-dependent signaling pathway.
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DOI：
10.1016/j.bbrc.2006.12.237
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发表时间：
2007-03
影响因子：
3.1
通讯作者：
T. Yonezawa;S. Hasegawa;Jae-Yong Ahn;Byung‐Yoon Cha;T. Teruya;H. Hagiwara;K. Nagai;J. Woo
中科院分区：
文献类型：
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作者：
T. Yonezawa;S. Hasegawa;Jae-Yong Ahn;Byung‐Yoon Cha;T. Teruya;H. Hagiwara;K. Nagai;J. Woo
有机锡化合物，如三丁基锡（TBT）和三苯基锡（TPT）已广泛应用于农业和工业领域。尽管已知这些化合物具有许多毒性作用，包括内分泌干扰作用，但它们对骨吸收的影响尚不清楚。在本研究中，我们使用小鼠单核细胞 RAW264.7 细胞研究了有机锡化合物，如单丁基锡 (MBT)、二丁基锡 (DBT)、TBT 和 TPT 对破骨细胞分化的影响。 MBT 和 DBT 没有影响，而 TBT 和 TPT 在浓度为 3-30nM 时剂量依赖性地抑制破骨细胞分化。使用视黄酸受体 (RAR) 特异性拮抗剂 Ro41-5253 治疗可恢复 TBT 和 TPT 对破骨细胞生成的抑制作用。 TBT和TPT减少核因子κB受体激活剂配体（RANKL）诱导的活化T细胞核因子（NFAT）c1的表达，并且Ro41-5253恢复了NFATc1表达的减少。我们的结果表明，TBT 和 TPT 通过 RAR 依赖性信号通路抑制 RANKL 诱导的 NFATc1 表达来抑制破骨细胞生成。
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 3–30nM. 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.