Magnolol Inhibits RANKL-Induced Osteoclast Differentiation of RAW 264.7 Macrophages through Heme Oxygenase-l-Dependent Inhibition of NFATc1 Expression
Magnolol Inhibits RANKL-Induced Osteoclast Differentiation of RAW 264.7 Macrophages through Heme Oxygenase-l-Dependent Inhibition of NFATc1 Expression
复制标题
DOI：
10.1021/np500663y
复制
发表时间：
2015-01-01
影响因子：
5.1
通讯作者：
Chou, Tz-Chong
中科院分区：
文献类型：
--
作者：
Lu, Sheng-Hua;Chen, Tso-Hsiao;Chou, Tz-Chong
Magnolol (1) isolated from Magnolia officinalis exhibits many beneficial effects such as anti-inflammatory and antioxidant activity. The aim of this study was to evaluate the effects of magnolol (1) on RANKL-induced osteoclast differentiation and investigate the underlying molecular mechanisms. Treatment with magnolol (1) significantly inhibited osteoclast differentiation of RAW 264.7 macrophages and bone-resorbing activity of osteoclasts in the RANKL-induced system. Moreover, RANKL-activated JNK/ERK/AP-1 and NF-kappa B signaling, ROS formation, and NFATc1 activation were attenuated by magnolol (1). A novel finding of this study is that magnolol (1) can increase heme oxygenase-1 (HO-1) expression and Nrf2 activation in RANKL-stimulated cells. Blocking HO-1 activity with tin protoporphyrin IX markedly reversed magnolol (1)-mediated inhibition of osteoclast differentiation, NFATc1 nuclear translocation, and MMP-9 activity, suggesting that HO-1 contributes to the attenuation of NFATc1-mediated osteoclastogenesis by magnolol (1). Therefore, the inhibitory effect of magnolol (1) on osteoclast differentiation is due to inhibition of MAPK/c-fos/AP-1 and NF-kappa B signaling as well as ROS production and up-regulation of HO-1 expression, which ultimately suppresses NFATc1 induction. These findings indicate that magnolol (1) may have potential to treat bone diseases associated with excessive osteoclastogenesis.
