类似于 ангиопоетин的8在骨衰老过程中控制骨质母细胞-脂肪细胞血统的承诺
Yaming Guo1,2,3, Zeqing Zhang1,2,3, Junyu He1,2,3
1Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
JCI insight
|October 21, 2025
概括
老化骨髓中酶干细胞 (MSCs) 从骨转向脂肪生产. 血管类蛋白8 (ANGPTL8) 驱动这种开关,影响骨衰老,并提供治疗点.
科学领域:
- 老年学是一门学科.
- 干细胞生物学 干细胞生物学
- 代谢调节 代谢调节 代谢调节 代谢调节
背景情况:
- 骨髓中的介质干细胞 (MSC) 随着年龄的增长而改变分化潜力,有利于脂肪生成而不是骨质母细胞生成.
- 驱动MSC中这种与年龄相关的细胞酸盐切换的分子机制在很大程度上是未知的.
研究的目的:
- 调查血管类蛋白8 (ANGPTL8) 在调节骨衰老期间MSC命运中的作用.
- 阐明 ANGPTL8 影响 BM 利基和 MSC 差异化的机制.
主要方法:
- 在小鼠中过度表达和转基因耗尽ANGPTL8.
- 评估骨质量和BM脂肪度.
- 对Wnt/β-catenin和PPARγ信号通路的分析.
- 使用 ANGPTL8 反感寡核酸的治疗.
主要成果:
- ANGPTL8的过度表达促进了MSC脂肪生成和骨质减少,而ANGPTL8的枯竭保护了骨并减少了脂肪积累.
- ANGPTL8 抑制了 BM 利基中的 Wnt/β-catenin 信号通路.
- 部分PPARγ抑制部分挽救了与ANGPTL8过度表达相关的MSC表型.
- 反感性寡核酸治疗改善了小鼠的衰老表型.
结论:
- ANGPTL8是BM领域老化相关变化的关键调节者.
- 在衰老过程中,ANGPTL8调解了MSC细胞命运转向脂肪生成的转变.
- ANGPTL8代表了与年龄相关的骨损失和代谢功能障碍的潜在治疗标.
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