Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways  

作　　者：Da-zhuang Lu Li-jun Zeng Yang Li Ran-li Gu Meng-long Hu Ping Zhang Peng Yu Xiao Zhang Zheng-wei Xie Hao Liu Yong-sheng Zhou 

机构地区：[1]Department of Prosthodontics,Peking University School and Hospital of Stomatology,Beijing,China [2]National Center of Stomatology,Beijing,China [3]National Clinical Research Center for Oral Diseases,Beijing,China [4]Beijing Key Laboratory of Digital Stomatology,Beijing,China [5]Department of Cariology and Endodontology,Peking University School and Hospital of Stomatology,Beijing,China [6]Peking University International Cancer Institute,Peking University Health Science Center,Peking University,Beijing,China [7]Central Laboratory,Peking University School and Hospital of Stomatology,Beijing,China [8]National Engineering Research Center of Oral Biomaterials and Digital Medical Devices,Beijing,China

出　　处：《Animal Models and Experimental Medicine》2024年第3期208-221,共14页动物模型与实验医学（英文）

基　　金：Beijing Natural Science Foundation,Grant/Award Number:L222145 and L222030;Emerging Engineering Interdisciplinary Project and the Fundamental Research Funds for the Central Universities,Grant/Award Number:PKU2022XGK008;Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological Innovation,Grant/Award Number:BMU2022PY010。

摘　　要：Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.

关 键 词：BMPs/SMAD bone loss cinobufotalin hBMMSCs OSTEOGENESIS OSTEOPOROSIS Wnt/β-catenin signaling pathways 

分 类 号：R580[医药卫生—内分泌]