Loureirin B suppresses RANKL-induced osteoclastogenesis and ovariectomized osteoporosis via attenuating NFATc1 and ROS activities

Loureirin B 通过减弱 NFATc1 和 ROS 活性来抑制 RANKL 诱导的破骨细胞生成和卵巢切除后骨质疏松症

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作者:Yuhao Liu, Chao Wang, Gang Wang, Youqiang Sun, Zhangrong Deng, Leilei Chen, Kai Chen, Jennifer Tickner, Jacob Kenny, Dezhi Song, Qingwen Zhang, Haibin Wang, Zhenqiu Chen, Chi Zhou, Wei He, Jiake Xu

Conclusions

Our findings confirm that LrB can attenuate osteoclast formation and OVX-induced osteoporosis. This novel and exciting discovery could pave the way for the development of LrB as a potential therapeutic treatment for osteoporosis.

Methods

We examined the effects of LrB on RANKL-induced osteoclast differentiation and bone resorption, and its impacts on RANKL-induced NFATc1 activation, calcium oscillations and reactive oxygen species (ROS) production in osteoclasts in vitro. We assessed the in vivo efficacy of LrB using an ovariectomy (OVX)-induced osteoporosis model, which was analyzed using micro-computed tomography (micro-CT) and bone histomorphometry.

Results

We found that LrB represses osteoclastogenesis, bone resorption, F-actin belts formation, osteoclast specific gene expressions, ROS activity and calcium oscillations through preventing NFATc1 translocation and expression as well as affecting MAPK-NFAT signaling pathways in vitro. Our in vivo study indicated that LrB prevents OVX-induced osteoporosis and preserves bone volume by repressing osteoclast activity and function. Conclusions: Our findings confirm that LrB can attenuate osteoclast formation and OVX-induced osteoporosis. This novel and exciting discovery could pave the way for the development of LrB as a potential therapeutic treatment for osteoporosis.

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