阿伦德罗纳特在胚胎发育模型中诱导骨变化
Wladimir Gushiken de Campos1, Rita Araújo2, Celso Augusto Lemos Júnior3
1Department of Stomatology, School of Dentistry, University of Sao Paulo, São Paulo, Brazil.
Toxicology and applied pharmacology
|August 31, 2023
概括
阿伦德罗纳酸以剂量依赖的方式对胚胎骨发育产生负面影响. 这种双酸盐药物减少了骨的形成和矿化,可能会在怀孕期间带来风险.
科学领域:
- 药理学 药理学是指药理学的学科.
- 发展生物学 发展生物学
- 整形外科 整形外科 整形外科
背景情况:
- 含有的双酸盐阿伦德罗酸盐广泛用于骨质疏松症,但它对骨质母细胞和胚胎发育的影响不太清楚.
- 阿伦德罗纳特可以穿过胎盘屏障,这对接受阿伦德罗纳特治疗的生育年龄的孕妇造成了担忧.
- 了解阿伦德罗纳酸对胚胎骨发育的影响是非常重要的,因为它具有潜在的原性作用.
研究的目的:
- 研究阿伦德罗纳酸对胚胎骨发育的剂量依赖性影响.
- 评估阿伦德罗纳酸对骨质原生和骨质细胞原生基因表达和骨发育中的炎症激活的影响.
- 通过转化动物模型评估胚胎发育期间阿伦德罗纳酸的安全性.
主要方法:
- 利用胚胎模型,将胚胎暴露在不同的阿伦德罗酸度 (1.5E-10M至1.5E-7M) 中,从骨质生成的第7天开始,持续4天.
- 进行了组织形态测量分析,包括体化学染色和微图分析,以评估骨发育和矿物化.
- 对骨质细胞发生,骨质发生和炎症标志物进行基因表达分析.
主要成果:
- 阿伦德罗纳特暴露表明了依赖剂量的骨生长和矿化抑制,骨体积和表面在1.5E-7M显著减少.
- 骨质细胞/骨质细胞基因和骨质母细胞/骨质母细胞基因的表达减少 (在1.5E-7M时减少30-50%) 表明骨质形成受损.
- 观察到炎症激活增加的证据,可能有助于观察到对骨发育的负面影响.
结论:
- 阿伦德罗纳酸对胚胎骨发育具有剂量依赖的负面影响.
- 这些发现凸显了胚胎骨形成的关键时期与阿伦德罗纳特暴露相关的潜在风险.
- 需要进一步的研究,以充分阐明阿伦德罗纳酸对胚胎发育影响的机制和临床影响.
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