Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling

• DOI: 10.3389/fendo.2023.1234563
• Publication Date: 2023-11-14T17:42:49Z
• Authors: Chunchun Xue; Huan Luo; Libo Wang; Qing Deng; Wenyun Kui; Weiwei Da; Lin Chen; Shuang Liu; Yongpeng Xue; Jiafan Yang; Lingxing Li; Wenlan Du; Qi Shi; Xiaofeng Li
• Keywords: Cathepsin K; Bone remodeling

Osteoporosis (OP), a prevalent public health concern primarily caused by osteoclast-induced bone resorption, requires potential therapeutic interventions. Natural compounds show as therapeutics for postmenopausal OP. Emerging evidence from in vitro osteoclastogenesis assay suggests that aconine (AC) serves an osteoclast differentiation regulator without causing cytotoxicity. However, the vivo functions of AC various OP models need clarification. To address this, we administered intraperitoneal injections to ovariectomy (OVX)-induced mice 8 weeks and found effectively reversed phenotype OVX mice, leading reduction vertebral loss restoration high turnover markers. Specifically, significantly suppressed decreasing expression osteoclast-specific genes such NFATc1 , c-Fos Cathepsin K Mmp9 . Importantly, can regulate ferroptosis suppressing Gpx4 upregulating Acsl4, which is achieved through inhibition phosphorylation I-κB p65 NF-κB signaling pathway. These findings suggest option managing signaling-mediated formation.