破骨细胞
组织蛋白酶K
骨吸收
骨质疏松症
体内
兰克尔
NF-κB
癌症研究
化学
骨重建
信号转导
细胞生物学
体外
药理学
激活剂(遗传学)
医学
内科学
生物
生物化学
受体
生物技术
作者
Chunchun Xue,Huan Luo,Libo Wang,Qing Deng,Wenyun Kui,Weiwei Da,Lin Chen,Shuang Liu,Y. Xue,Jiafan Yang,Lingxing Li,Wenlan Du,Qi Shi,Xiaofeng Li
标识
DOI:10.3389/fendo.2023.1234563
摘要
Osteoporosis (OP), a prevalent public health concern primarily caused by osteoclast-induced bone resorption, requires potential therapeutic interventions. Natural compounds show potential as therapeutics for postmenopausal OP. Emerging evidence from in vitro osteoclastogenesis assay suggests that aconine (AC) serves as an osteoclast differentiation regulator without causing cytotoxicity. However, the in vivo functions of AC in various OP models need clarification. To address this, we administered intraperitoneal injections of AC to ovariectomy (OVX)-induced OP mice for 8 weeks and found that AC effectively reversed the OP phenotype of OVX mice, leading to a reduction in vertebral bone loss and restoration of high bone turnover markers. Specifically, AC significantly suppressed osteoclastogenesis in vivo and in vitro by decreasing the expression of osteoclast-specific genes such as NFATc1, c-Fos, Cathepsin K, and Mmp9. Importantly, AC can regulate osteoclast ferroptosis by suppressing Gpx4 and upregulating Acsl4, which is achieved through inhibition of the phosphorylation of I-κB and p65 in the NF-κB signaling pathway. These findings suggest that AC is a potential therapeutic option for managing OP by suppressing NF-κB signaling-mediated osteoclast ferroptosis and formation.
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