Toosendanin inhibits osteoclast formation and alleviate postmenopausal osteoporosis by regulating the p38 signaling pathway
Toosendanin inhibits osteoclast formation and alleviate postmenopausal osteoporosis by regulating the p38 signaling pathway
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DOI：
10.1016/j.intimp.2023.109745
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发表时间：
2023-01-24
影响因子：
5.6
通讯作者：
Ouyang, Zhengxiao
中科院分区：
文献类型：
--
作者：
Tan, Tingting;Li, Tao;Ouyang, Zhengxiao
破骨细胞和成骨细胞之间的平衡破坏可能导致骨质疏松症等骨疾病。众所周知，RANKL-RANK 信号在激活破骨细胞中起着至关重要的作用。在此，我们探讨了川楝素 (TSN) 在骨质疏松症中的治疗作用，结果表明，TSN 在体外减弱 RANKL 刺激的破骨细胞生成和破骨细胞特异性基因表达。生物信息学预测TSN可以干扰p38亚基并调节MAPK级联，我们通过蛋白质印迹进一步验证并证明TSN显着抑制RANKL诱导的p38信号传导。在卵巢切除小鼠模型中，TSN 有效抑制 TRAP 阳性破骨细胞的形成，并对骨丢失具有保护作用。总而言之，这些数据表明 TSN 靶向 p38 激活来抑制破骨细胞生成，表明 TSN 未来可能用于治疗骨质疏松症。
Disruption of the balance between osteoclasts and osteoblasts could lead to bone diseases including osteoporosis. It's well known that RANKL-RANK signaling plays a vital role in activating osteoclasts. Herein, we explored the therapeutic effects of toosendanin (TSN) in osteoporosis, showing that TSN attenuated RANKL-stimulated osteoclastogenesis and osteoclast-specific gene expression in vitro. Bioinformatics predicted that TSN could interfere p38 subunits and regulate the MAPK cascade, and we further verified and demonstrated that TSN significantly inhibited RANKL-induced p38 signaling through western blot. In ovariectomized mouse model, TSN effectively inhibited the formation of TRAP-positive osteoclasts and exhibited protective effect against bone loss. Altogether, these data indicate that TSN targeted p38 activation to inhibit osteoclastogenesis, suggesting the possible therapeutic use of TSN in osteoporosis in the future.