机构：[1]Department of Spine Surgery, TongRen Hospital, School of Medicine, Shanghai Jiao Tong University, 1111 Xianxia Road, Shanghai 200336, People’s Republic of China
The treatment for osteoporosis involves inhibiting bone resorption and osteoclastogenesis. Glycyrrhizin (GLY) is a triterpenoid saponin glycoside known to be as the most medically efficacious component of the licorice plant. It has strong anti-inflammatory, antioxidant, and antitumor properties. We investigated the effect of GLY on osteoclastogenesis, bone resorption, and intracellular oxidative stress and its molecular mechanisms. In vitro osteoclastogenesis assays were performed using bone marrow monocytes with and without glycyrrhizin. We also evaluated the effects of glycyrrhizin on the secretion of TNF-alpha, IL-1 beta, and IL-6 in LPS-stimulated RAW 264.7 cells using ELISA. The effects of glycyrrhizin on the expression of osteoclast-related genes, such as Nfatc1, c-fos, Trap, and cathepsin K (CK), were investigated by RT-PCR. Intracellular reactive oxygen species (ROS) were detected in receptor activator of nuclear factor kappa-I' ligand (RANKL)-stimulated osteoclasts in the presence and absence of glycyrrhizin. During the inhibition of osteoclastogenesis by glycyrrhizin, phosphorylation of AMPK, Nrf2, NF-kappa B, and MAPK was analyzed using western blotting. Our results showed that glycyrrhizin significantly inhibited RANKL-induced osteoclastogenesis, downregulated the expression of NFATc1, c-fos, TRAP, CK, DC-STAMP, and OSCAR, and inhibited p65, p38, and JNK. Glycyrrhizin was found to significantly decrease the secretion of inflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6). Additionally, glycyrrhizin reduced the formation of ROS in osteoclasts by inducing AMPK phosphorylation and nuclear transfer of NRF2, resulting in an upregulation of antioxidant enzymes, such as HO-1, NQO-1, and GCLC. In summary, we found that glycyrrhizin inhibited RANKL-induced osteoclastogenesis. It was also indicated that glycyrrhizin could reduce oxidative stress by inhibiting the MAPK and NF-kappa B pathways and activating the AMPK/NRF2 signaling. Therefore, glycyrrhizin may be used as an effective therapeutic agent against osteoporosis and bone resorption.
第一作者机构：[1]Department of Spine Surgery, TongRen Hospital, School of Medicine, Shanghai Jiao Tong University, 1111 Xianxia Road, Shanghai 200336, People’s Republic of China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Li Zhikun,Chen Chao,Zhu Xiaodong,et al.Glycyrrhizin Suppresses RANKL-Induced Osteoclastogenesis and Oxidative Stress Through Inhibiting NF-kappa B and MAPK and Activating AMPK/Nrf2[J].CALCIFIED TISSUE INTERNATIONAL.2018,103(3):324-337.doi:10.1007/s00223-018-0425-1.
APA：
Li, Zhikun,Chen, Chao,Zhu, Xiaodong,Li, Yifan,Yu, Ronghua&Xu, Wei.(2018).Glycyrrhizin Suppresses RANKL-Induced Osteoclastogenesis and Oxidative Stress Through Inhibiting NF-kappa B and MAPK and Activating AMPK/Nrf2.CALCIFIED TISSUE INTERNATIONAL,103,(3)
MLA：
Li, Zhikun,et al."Glycyrrhizin Suppresses RANKL-Induced Osteoclastogenesis and Oxidative Stress Through Inhibiting NF-kappa B and MAPK and Activating AMPK/Nrf2".CALCIFIED TISSUE INTERNATIONAL 103..3(2018):324-337
