破骨细胞
兰克尔
骨吸收
炎症
骨质疏松症
骨保护素
MAPK/ERK通路
受体
癌症研究
促炎细胞因子
内分泌学
化学
NF-κB
信号转导
内科学
医学
细胞生物学
激活剂(遗传学)
生物
作者
Xiaodi Zhang,Zhengfang Sun,Ying Zhang,Liuzhu Pan,Wei Jiang,Hui Dong,Zhengxin Jin,Jianning Kang,Ronghan Liu,Bin Ning
标识
DOI:10.1016/j.bcp.2023.115516
摘要
Osteoporosis is a common inflammaging-related condition, where long-term accumulation of pro-inflammatory cytokines causes massive bone loss. Periplocin, a cardiotonic steroid isolated from Periploca forrestii, has been proved to reduce inflammation in several inflammatory diseases, such as rheumatoid arthritis. However, its effect and mechanism of inflammation in osteoporosis, in which pro-inflammatory factors accelerate bone loss, has not been well demonstrated. In this study, periplocin attenuated receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation of bone marrow-derived macrophages (BMMs) and RAW264.7 cells in vitro. It reduced osteoclast numbers and bone resorption in a concentration- and time-dependent manner. Further, periplocin treatment resulted in reduced bone loss on mice with ovariectomy-induced osteoporosis in vivo. By transcriptome sequencing, periplocin was indicated to function through inhibition of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways and attenuating interactions between NF-κB and nuclear factor of activated T-cells 1 (NFATc1). It was further detected to bind low density lipoprotein receptor-related protein 4 (LRP4) in osteoclasts to exert anti-inflammatory and anti-osteoclastic effects. Overall, the findings have highlighted a better understanding for the anti-inflammatory and anti-osteoclastic role of periplocin in osteoporosis and its mechanism, bringing new possibilities for osteoporosis treatment.
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