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

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

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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.

BMPs/SMADbone losscinobufotalinhBMMSCsosteogenesisosteoporosisWnt/β-catenin signaling pathways

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

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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

Department of Cariology and Endodontology,Peking University School and Hospital of Stomatology,Beijing,China

Peking University International Cancer Institute,Peking University Health Science Center,Peking University,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

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Beijing Natural Science FoundationPeking University Medicine Fund of Fostering Young Scholars'Scientific&Technological InnovationEmerging Engineering Interdisciplinary Project and the Fundamental Research Funds for the Central Universities

L222145&L222030BMU2022PY010PKU2022XGK008

2024

10.1002/ame2.12359

动物模型与实验医学(英文)
中国实验动物学会,中国医学科学院医学实验动物研究所

动物模型与实验医学(英文)

ISSN：2096-5451
年,卷(期)：2024.7(3)
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