实用临床医药杂志2026，Vol.30Issue(5)：40-47,8.DOI:10.7619/jcmp.20253616
网络毒理学与分子对接技术分析松弛素信号通路在利塞膦酸钠致颌骨骨坏死中的作用
Analysis of the role of the relaxin signaling pathway in risedronate sodium-induced osteonecrosis of the jaw through network toxicology and molecular docking techniques
摘要
Abstract
Objective To explore the potential mechanism by which risedronate sodium induces os-teonecrosis of the jaw(ONJ)using network toxicology and molecular docking methods.Methods Poten-tial targets of risedronate sodium and ONJ were screened based on the Genecards,MalaCards,Com-parative Toxicogenomics Database,and TargetNet databases.The GeneMania online platform was uti-lized to construct a protein-protein interaction network to obtain potential core targets.Core regulatory targets were screened through dimensionality reduction clustering and meta-path analysis.Gene ontol-ogy(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were con-ducted to identify key pathways enriched by the core targets.The structural files of risedronate sodium and the 3D structures of core regulatory target proteins were obtained from PubChem and the Brookhaven Protein Database,respectively,and molecular docking was performed using the CB-Dock2 platform.Results A total of 15 common targets between ONJ and risedronate sodium were identified.Through PPI network analysis,34 potential core targets were obtained,and 18 core targets were identified after dimensionality reduction clustering.GO and KEGG results revealed that the core targets were mainly enriched in the relaxin signaling pathway,estrogen signaling pathway,and arginine biosynthesis.Meta-path analysis further confirmed four core regulatory targets(NOS1,NOS2,NOS3,and SRC),which were enriched in the relaxin signaling pathway.Molecular docking results demonstrated that risedronate sodium had good binding ability to the core regulatory targets.Conclusion By integrating dimensionality reduction clustering and molecular docking methods through meta-path analysis,this study revealed the potential mechanism by which risedronate sodium can activate the relaxin signaling pathway via NOS1,NOS2,NOS3,and SRC to induce ONJ.This finding provides a novel,multidimensional analytical paradigm for studying the bone toxicity mecha-nisms of bisphosphonates and offers a theoretical basis for subsequent cellular and animal experiments.关键词
利塞膦酸钠/双膦酸盐/颌骨坏死/网络毒理学/分子对接/松弛素信号通路/一氧化氮合酶/蛋白质-蛋白质互作网络Key words
risedronate sodium/bisphosphonate/osteonecrosis of the jaw/network toxicology/molecular docking/relaxin signaling pathway/nitric oxide synthase/protein-protein interaction network分类
医药卫生引用本文复制引用
梁艺馨,林红晓,张伟,石晓琦..网络毒理学与分子对接技术分析松弛素信号通路在利塞膦酸钠致颌骨骨坏死中的作用[J].实用临床医药杂志,2026,30(5):40-47,8.基金项目
2024年连云港市卫生健康面上科技项目(202406) （202406）
