Cinobufotalin Prevents Bone Loss Induced by Ovariectomy in Mice Through the BMPs/SMAD and Wnt/β-catenin Signaling Pathways

Overview

Journal Animal Model Exp Med

Date 2023 Nov 28

PMID 38013618

Authors

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

Affiliations

Soon will be listed here.

Abstract

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 (0.25 mg/kg in vivo, 0.05 μM 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.

Citing Articles

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

Lu D, Zeng L, Li Y, Gu R, Hu M, Zhang P Animal Model Exp Med. 2023; 7(3):208-221.

PMID: 38013618 PMC: 11228090. DOI: 10.1002/ame2.12359.

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