DOI: 10.1002/ame2.12359
Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways
Da-zhuang Lu1
Li-jun Zeng1
Yang Li1
Ran-li Gu1
Meng-long Hu1
Ping Zhang1
Peng Yu2
Xiao Zhang1
Zheng-wei Xie3
Hao Liu4
Yong-sheng Zhou5
1.Department of Prosthodontics,Peking University School and Hospital of Stomatology,Beijing,China;National Center of Stomatology,Beijing,China;National Clinical Research Center for Oral Diseases,Beijing,China;Beijing Key Laboratory of Digital Stomatology,Beijing,China2.National Center of Stomatology,Beijing,China;National Clinical Research Center for Oral Diseases,Beijing,China;Beijing Key Laboratory of Digital Stomatology,Beijing,China;Department of Cariology and Endodontology,Peking University School and Hospital of Stomatology,Beijing,China3.Peking University International Cancer Institute,Peking University Health Science Center,Peking University,Beijing,China4.Department of Prosthodontics,Peking University School and Hospital of Stomatology,Beijing,China;National Center of Stomatology,Beijing,China;National Clinical Research Center for Oral Diseases,Beijing,China;Beijing Key Laboratory of Digital Stomatology,Beijing,China;Central Laboratory,Peking University School and Hospital of Stomatology,Beijing,China5.Department of Prosthodontics,Peking University School and Hospital of Stomatology,Beijing,China;National Center of Stomatology,Beijing,China;National Clinical Research Center for Oral Diseases,Beijing,China;Beijing Key Laboratory of Digital Stomatology,Beijing,China;Central Laboratory,Peking University School and Hospital of Stomatology,Beijing,China;National Engineering Research Center of Oral Biomaterials and Digital Medical Devices,Beijing,China
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 vari-ous 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 morphologi-cal 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 (0.25 mg/kg in vivo,0.05 μ M in vitro) of CB could ef-fectively 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 estro-gen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.
机标关键词：cateninthroughpathwayssmadbmpslossmicebone
论文发表日期：2024-06-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：14( 208-221 )
英文信息