纤维细胞生长因子23介导的骨质疏松症调节:通过孟德尔随机化和体外研究评估
Xiang Zhang1,2,3, Jin Xu1,2,3,4,5,6
1Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Journal of cellular and molecular medicine
|July 26, 2024
概括
纤维细胞生长因子23 (FGF23) 水平升高与骨质疏松症的更高风险有因果关系. 此外,FGF23还抑制了骨细胞分化,使病情恶化.
科学领域:
- 内分泌学 在内分泌学.
- 骨生物学 骨生物学 骨生物学
- 遗传学 遗传学 是一个
背景情况:
- 骨质疏松 (OP) 病原发生涉及复杂的因素,包括纤维细胞生长因子23 (FGF23),α-Klotho和FGF受体-1 (FGFR1),但它们的确切作用仍在争论中.
- 现有的研究缺乏关于FGF23,α-Klotho,FGFR1和OP之间的因果关系的最终共识.
研究的目的:
- 使用孟德尔随机化 (MR) 分析阐明FGF23,α-Klotho,FGFR1和骨质疏松症之间的因果关系.
- 研究FGF23在体外对人类骨髓介质干细胞 (hBMSCs) 增殖和骨质分化的作用.
主要方法:
- 孟德尔随机化 (MR) 分析利用全基因组关联研究 (GWAS) 数据集.
- 逆方差加权 (IVW) 方法用于确定主要终点的赔率比率 (OR).
- 在体外实验中,FGF23模仿或siRNA-FGF23稳定转化为hBMSC,以评估增殖和骨质原生标志物 (RUNX2,OCN,OSX,ALP活性,矿化结节).
主要成果:
- 核磁共振分析显示,血清FGF23水平与脚跟 (OR=0.919) 和大腿部 (OR=0.751) 的骨矿物质密度 (BMD) 降低之间存在显著的相关性.
- 与对照组相比,OP患者的部部FGF23表达显著增加 (p < 0.0001).
- 在体外,hBMSCs中的FGF23过度表达降低了增殖,关键骨质基因表达,矿化结节形成和ALP活性,而FGF23沉默显示了相反的效果.
结论:
- 增加的FGF23水平与骨质疏松症的风险增加有关.
- 过度表达FGF23显著抑制了hBMSCs的骨质分化,可能会加剧OP的病理过程.
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