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辛伐他汀和氟伐他汀在器官型骨模型中的成骨潜力

Osteogenic Potential of Simvastatin and Fluvastatin in an Organotypic Bone Model.

作者信息

Poskevicius Lukas, Martin Victor, Costa Guilherme, Juodžbalys Gintaras, Sousa Gomes Pedro

机构信息

Faculty of Odontology, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania.

BoneLab, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal.

出版信息

Pharmaceuticals (Basel). 2025 Jun 21;18(7):939. doi: 10.3390/ph18070939.

DOI:10.3390/ph18070939
PMID:40732229
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12299731/
Abstract

: Statins, widely prescribed for their lipid-lowering properties, also exert pleiotropic effects on various tissues, including bone. However, their osteogenic potential remains poorly defined due to variability in statin type, dosage, and experimental models. This study investigates the osteogenic effects of fluvastatin (FV) and simvastatin (SV) on the ex vivo embryonic chick femur model. : Femora were cultured with logarithmic concentrations (0.1-10 µM) of FV or SV, followed by characterization via microcomputed tomography, histological analysis, and quantitative gene expression. : Both statins enhanced osteogenic outcomes at low concentrations (0.1-1 µM), as evidenced by increased bone volume fraction, trabecular organization, collagen matrix maturation, and mineral deposition. Molecular analysis revealed upregulation of key osteogenic markers-RUNX2, SPP1, and COL1A2-with no significant change in chondrogenic markers (SOX9, ACAN), indicating selective activation of osteogenic pathways. In contrast, higher-dose treatment (10 µM) attenuated these effects. : These findings underscore the dose-dependent osteoinductive potential of statins and support their application in bone repair strategies within carefully defined therapeutic windows.

摘要

他汀类药物因其降脂特性而被广泛处方,它还对包括骨骼在内的各种组织产生多效性作用。然而,由于他汀类药物类型、剂量和实验模型的差异,它们的成骨潜力仍未明确界定。本研究调查了氟伐他汀(FV)和辛伐他汀(SV)对离体鸡胚股骨模型的成骨作用。

股骨用对数浓度(0.1 - 10 μM)的FV或SV培养,随后通过微型计算机断层扫描、组织学分析和定量基因表达进行表征。

两种他汀类药物在低浓度(0.1 - 1 μM)时均增强了成骨效果,表现为骨体积分数增加、小梁组织改善、胶原基质成熟和矿物质沉积。分子分析显示关键成骨标志物RUNX2、SPP1和COL1A2上调,而软骨生成标志物(SOX9、ACAN)无显著变化,表明成骨途径的选择性激活。相比之下,高剂量治疗(10 μM)减弱了这些作用。

这些发现强调了他汀类药物剂量依赖性的骨诱导潜力,并支持它们在精心定义的治疗窗口内应用于骨修复策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ef/12299731/3919dd36d193/pharmaceuticals-18-00939-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ef/12299731/9ef6d3b65973/pharmaceuticals-18-00939-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ef/12299731/4931ab75b581/pharmaceuticals-18-00939-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ef/12299731/98bcc762a846/pharmaceuticals-18-00939-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ef/12299731/3919dd36d193/pharmaceuticals-18-00939-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ef/12299731/9ef6d3b65973/pharmaceuticals-18-00939-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ef/12299731/4931ab75b581/pharmaceuticals-18-00939-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ef/12299731/98bcc762a846/pharmaceuticals-18-00939-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ef/12299731/3919dd36d193/pharmaceuticals-18-00939-g004.jpg

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