Pinoresinol diglucoside mitigates dexamethasone-induced osteoporosis and chondrodysplasia in zebrafish

IF 3.3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Toxicology and applied pharmacology Pub Date : 2024-03-01 DOI:10.1016/j.taap.2024.116884
Yuhua Zuo , Chao Chen , Fasheng Liu , Hongmei Hu , Si Dong , Qinyuan Shen , Junquan Zeng , Ling Huang , Xinjun Liao , Zigang Cao , Zilin Zhong , Huiqiang Lu , Jianjun Chen
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Abstract

Background

The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly.

Objective

This study aimed to evaluate the protective properties of pinoresinol diglucoside (PDG), an active constituent of Eucommia ulmoides, against dexamethasone-induced osteoporosis and chondrodysplasia.

Methods

A zebrafish model of osteoporosis was established by exposing larval zebrafish to dexamethasone. The impact of PDG on bone mineralization was assessed through alizarin red and calcein staining. Alkaline phosphatase activity was quantified to evaluate osteoblast function. The influence of PDG on chondrogenesis was estimated using alcian blue staining. Fluorescence imaging and motor behavior analysis were employed to assess the protective effect of PDG on the structure and function of dexamethasone-induced skeletal teratogenesis. qPCR determined the expression of osteogenesis and Wnt signaling-related genes. Molecular docking was used to assess the potential interactions between PDG and Wnt receptors.

Results

PDG significantly increased bone mineralization and corrected spinal curvature and cartilage malformations in the zebrafish model. Furthermore, PDG enhanced swimming abilities compared to the model group. PDG mitigated dexamethasone-induced skeletal abnormalities in zebrafish by upregulating Wnt signaling, showing potential interaction with Wnt receptors FZD2 and FZD5.

Conclusion

PDG mitigates dexamethasone-induced osteoporosis and chondrodysplasia by promoting bone formation and activating Wnt signaling.

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松脂醇二葡萄糖苷可减轻地塞米松诱导的斑马鱼骨质疏松症和软骨发育不良。
背景:全球老龄人口的增加导致了老年人骨质疏松症发病率的上升:本研究旨在评估杜仲的活性成分松脂醇二葡萄糖苷(PDG)对地塞米松诱导的骨质疏松症和软骨发育不良的保护作用:方法:通过让幼年斑马鱼接触地塞米松,建立了斑马鱼骨质疏松症模型。通过茜素红和钙黄绿素染色评估 PDG 对骨矿化的影响。通过量化碱性磷酸酶活性来评估成骨细胞的功能。使用阿尔金山蓝染色法评估了 PDG 对软骨生成的影响。利用荧光成像和运动行为分析评估了 PDG 对地塞米松诱导的骨骼畸形发生的结构和功能的保护作用。采用分子对接法评估了 PDG 与 Wnt 受体之间的潜在相互作用:结果:在斑马鱼模型中,PDG能明显增加骨矿化,纠正脊柱弯曲和软骨畸形。此外,与模型组相比,PDG 提高了游泳能力。PDG 通过上调 Wnt 信号,缓解了地塞米松诱导的斑马鱼骨骼异常,显示出与 Wnt 受体 FZD2 和 FZD5 的潜在相互作用:结论:PDG通过促进骨形成和激活Wnt信号,缓解地塞米松诱导的骨质疏松症和软骨发育不良。
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来源期刊
CiteScore
6.80
自引率
2.60%
发文量
309
审稿时长
32 days
期刊介绍: Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.
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