Suppression of NFATc1 through NF-kB/PI3K signaling pathway by Oleandrin to inhibit osteoclastogenesis and bone resorption  

作　　者：Zhikun Li Kai Chen Qifeng Yu Yifan Li Shichao Tong Ruijun Xu Ruixi Hu Yi Zhang Wei Xu 

机构地区：[1]Department of Orthopedic,TongRen Hospital,School of Medicine,Shanghai Jiao Tong University,1111 Xianxia Road,Shanghai 200336,People’s Republic of China [2]Department of Orthopaedic,Naval Medical University First Affiliated Hospital,200433,168 Changhai Road,Yangpu District,Shanghai,People’s Republic of China [3]Department of Traditional Chinese Medicine,TongRen Hospital,School of Medicine,Shanghai Jiao Tong University,1111 Xianxia Road,Shanghai 200336,People’s Republic of China

出　　处：《Engineered Regeneration》2024年第3期342-349,共8页再生工程（英文）

基　　金：National Natural Science Foundation of China(82272165);Shanghai Municipal Commission of Health and Family Planning’s Science and Research Fund(202040141);Shanghai Municipality Science and Technology Commission(20ZR1451800,22ZR1457200);Shanghai Municipal Health Commission(2022YQ006);Shanghai Tongren Hospital(TRKYRC-xx202203).

摘　　要：Inflammation can initiate osteolysis,which is the breakdown of bone by fully developed osteoclasts.The com-pound Oleandrin is recognized for its effects against inflammation and tumors.Our objective was to examine the effects of Oleandrin on osteoclastogenesis and osteolysis,both in vitro and in vivo.In vitro,the impact of Oleandrin on osteoclastogenesis was assessed using CCK-8 assays,TRAP staining,and bone resorption assays.Ad-ditionally,a mouse model of osteolysis caused by LPS injection into the calvaria was used to conduct an in vivo investigation,examining bone histomorphology,histology,and immunohistochemistry.In vitro,concentrations of 5 nM and 10 nM of Oleandrin were found to be non-cytotoxic based on the results obtained.In vitro,Olean-drin hindered the osteoclastogenesis and bone resorption induced by RANKL.Oleandrin successfully inhibited the phosphorylation of NF-κB p65 and PI3K p85 in osteolytic tissue,thereby suppressing LPS-induced inflammatory osteolysis in mice calvaria during the in vivo study.Furthermore,the Oleandrin-treated group exhibited a note-worthy decrease in the expression level of NFATc1,which is a crucial controller of osteoclastogenesis.To sum up,our discoveries indicate that Oleandrin could hinder osteoclastogenesis and bone resorption,thereby having the ability to suppress inflammation-induced osteolysis.The underlying mechanism involves the NF-κB/PI3K pathway and inhibition of NFATc1 activation.Therefore,the findings suggest that Oleandrin holds potential as a therapeutic remedy for osteolytic ailments.

关 键 词：OSTEOCLASTOGENESIS OSTEOLYSIS NF-κB PI3K Oleandrin NFATc1 

分 类 号：R68[医药卫生—骨科学]