去卵巢大鼠
化学
破骨细胞
内分泌学
骨吸收
内科学
骨质疏松症
兰克尔
成骨细胞
骨保护素
运行x2
激活剂(遗传学)
过氧化物酶体增殖物激活受体
骨矿物
受体
信号转导
细胞生物学
生物化学
医学
生物
激素
体外
作者
Yining Li,Chao Liu,Xiao Han,Xiaobing Ren,Bao Li,Lijie Lei,Yongkang Wu,Quanjie Li,Yuyan Zhang,Jing Zhang,Weizhi Wang,Yuhao Zhang,Shunwang Li,Chenyin Wang,Xinwei Wei,Jian Wang,Zong‐Gen Peng,Xu Yang,Shuyi Si
标识
DOI:10.1016/j.bioorg.2024.107364
摘要
Osteoporosis is particularly prevalent among postmenopausal women and the elderly. In the present study, we investigated the effect of the novel small molecule E0924G (N-(4-methoxy-pyridine-2-yl)-5-methylfuran-2-formamide) on osteoporosis. E0924G significantly increased the protein expression levels of osteoprotegerin (OPG) and runt-related transcription factor 2 (RUNX2), and thus significantly promoted osteogenesis in MC3T3-E1 cells. E0924G also significantly decreased osteoclast differentiation and inhibited bone resorption and F-actin ring formation in receptor activator of NF-κB ligand (RANKL)-induced osteoclasts from RAW264.7 macrophages. Importantly, oral administration of E0924G in both ovariectomized (OVX) rats and SAMP6 senile mice significantly increased bone mineral density and decreased bone loss compared to OVX controls or SAMR1 mice. Further mechanistic studies showed that E0924G could bind to and then activate peroxisome proliferator-activated receptor delta (PPARδ), and the pro-osteoblast effect and the inhibition of osteoclast differentiation induced by E0924G were significantly abolished when PPARδ was knocked down or inhibited. In conclusion, these data strongly suggest that E0924G has the potential to prevent OVX-induced and age-related osteoporosis by dual regulation of bone formation and bone resorption through activation of the PPARδ signaling pathway.
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