糖尿病通过Foxo1介导的纤毛发育中断损害骨折愈合
Zahra Chinipardaz1,2,3, Gongsheng Yuan1, Min Liu2
1Department of Basic and Translation Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Cell death discovery
|August 17, 2023
概括
糖尿病通过增加Foxo1损害骨折愈合,从而减少IFT80和初级毛. 恢复乳毛或抑制Foxo1可能会改善糖尿病患者的骨修复.
科学领域:
- 生物医学工程 生物医学工程
- 分子生物学分子生物学
- 整形外科 整形外科 整形外科
背景情况:
- 糖尿病与骨折愈合受损有关.
- 福克索1 (叉头盒蛋白O1) 的升高调节和受损的纤毛发育与这种缺陷有关.
- 在骨折修复中,糖尿病,Foxo1和乳毛功能障碍之间的确切机制尚未完全理解.
研究的目的:
- 阐明糖尿病诱导的Foxo1上调调节损害骨折愈合的机制.
- 调查Foxo1在调节IFT80表达和糖尿病患者骨修复期间初级乳毛形成中的作用.
- 评估针对Foxo1或乳毛形成的治疗潜力,以改善糖尿病骨折愈合.
主要方法:
- 在小鼠中,斯特佐托 (STZ) 诱导的1型糖尿病 (T1DM) 模型.
- 分析Foxo1,IFT80表达,以及大腿骨折骨中的初级毛.
- 在骨质母细胞中使用OSXcretTA小鼠的Foxo1f/f基因切除.
- 在骨质细胞上使用先进的糖化终产物 (AGEs) 的体外研究.
主要成果:
- STZ诱导的T1DM显著增加了Foxo1的表达,减少了IFT80,并减少了骨折骨中的初级毛.
- 在骨质母细胞中的Foxo1切除可以挽救IFT80表达,恢复纤毛发育,改善糖尿病小鼠的骨形成和强度.
- 在体外,AGE降低了骨质细胞纤维的形成和矩阵的产生,通过Foxo1删除挽救了这些效应.
- AGEs增加了Foxo1活性,抑制了IFT80表达和眼的形成.
结论:
- 糖尿病通过Foxo1-介导的IFT80抑制和初级毛形成,损害骨折愈合,导致骨质发生缺陷.
- 向Foxo1或恢复乳毛形成是增强糖尿病患者骨折愈合的潜在治疗策略.
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