Zoledronic Acid Inhibits Lipopolysaccharide-Induced Osteoclastogenesis by Suppressing Macrophage NLRP3-Mediated Autophagy Pathway

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease Pub Date : 2024-12-16 DOI:10.1002/iid3.70094

Yuting Cheng, Guanjuan Liu, Xiaolin Huang, Yue Xiong, Na Song, Zheqing An, Wei Hong, Chidchanok Leethanakul, Bancha Samruajbenjakun, Jian Liao

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Abstract

Introduction

Inflammatory factors leading to bone loss significantly increase the risk of tooth loosening or implantation failure. Zoledronic acid (ZOL) is a widely used medication for effectively inhibiting excessive bone destruction, but its effect on alleviating inflammatory bone loss remains to be elucidated. In this study, we investigated whether ZOL alleviates inflammatory bone resorption through immunomodulatory effect.

Methods

The viability of the cells was evaluated by Cell Counting Kit 8 (CCK8) assay. Osteoclast (OC) differentiation and function were determined by tartrate-resistant acid phosphatase (TRAP) staining and bone resorption pits assays, respectively. Autophagosomes and actin ring structures of OC were observed using transmission electron microscopy (TEM) and F-actin ring staining, respectively. The microstructure in mice maxillary alveolar bone model was observed by micro computed tomography (Miro-CT). Reverse transcription-quantitative PCR (RT-qPCR) to detect the mRNA expression of osteoclast-related genes and Western blot (WB) analysis to evaluate the protein expression levels of autophagy-related proteins and the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3)-related proteins in pre-OCs.

Results

The findings indicated that ZOL hindered lipopolysaccharide (LPS)-mediated OC differentiation, formation, bone resorption activity and autophagosome levels. Furthermore, ZOL diminished the expression of genes associated with OC. And the expression of proteins ATG7, LC3II, Beclin1, NLRP3-related proteins and tumor necrosis factor-α (TNF-α) protein were markedly decreased while P62 was increased, especially in the 1 μM ZOL group or MCC950 + ZOL group.

Conclusions

ZOL has a certain immunomodulatory effect that exhibits anti-inflammatory properties at lower concentrations, which can weaken LPS-induced OCs differentiation and function, and NLRP3-mediated autophagy pathway may participate in this process.

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唑来膦酸通过抑制巨噬细胞NLRP3介导的自噬途径抑制脂多糖诱导的破骨细胞生成

导言：导致骨质流失的炎症因素会显著增加牙齿松动或种植失败的风险。唑来膦酸（ZOL）是一种广泛使用的有效抑制过度骨破坏的药物，但其减轻炎症性骨质流失的作用仍有待阐明。在本研究中，我们研究ZOL是否通过免疫调节作用减轻炎症性骨吸收。方法：采用细胞计数试剂盒8 （CCK8）法测定细胞活力。通过抗酒石酸酸性磷酸酶（TRAP）染色和骨吸收坑测定，分别测定破骨细胞（OC）分化和功能。透射电镜（TEM）和F-actin环染色分别观察OC的自噬体和肌动蛋白环结构。采用显微计算机断层扫描（micro - ct）观察小鼠上颌牙槽骨模型的显微结构。逆转录定量PCR （RT-qPCR）检测破骨细胞相关基因mRNA表达，Western blot （WB）分析自噬相关蛋白和nod样受体家族pyrin domain containing protein 3 （NLRP3）相关蛋白在ocs前期的表达水平。结果：ZOL可抑制脂多糖（LPS）介导的OC分化、形成、骨吸收活性和自噬体水平。此外，ZOL降低了与OC相关基因的表达。ATG7、LC3II、Beclin1、nlrp3相关蛋白和肿瘤坏死因子-α (TNF-α)蛋白的表达明显降低，P62表达明显升高，其中以1 μM ZOL组和MCC950 + ZOL组表达最为明显。结论：ZOL具有一定的免疫调节作用，在低浓度下具有抗炎作用，可减弱lps诱导的OCs分化和功能，nlrp3介导的自噬通路可能参与了这一过程。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunity, Inflammation and Disease Medicine-Immunology and Allergy

CiteScore

3.60

自引率

0.00%

发文量

146

审稿时长

8 weeks

期刊介绍： Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including: • cellular and molecular immunology • clinical immunology • allergy • immunochemistry • immunogenetics • immune signalling • immune development • imaging • mathematical modelling • autoimmunity • transplantation immunology • cancer immunology

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