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内皮细胞衍生乳酸触发骨介质干细胞的希斯乳酸化减轻骨质疏松症
Jinhui Wu1, Miao Hu2, Heng Jiang1
1Department of Orthopedics, Changzheng Hospital, Naval Medical University, Shanghai, 200003, P. R. China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|September 27, 2023
概括
由PKM2 (pyruvate kinase M2) 调节的内皮细胞糖解对于骨形成和预防骨质疏松症至关重要. 从这些细胞中减少的乳酸会损害骨髓干细胞分化,但运动可能有帮助.
科学领域:
- 血管生物学 血管生物学
- 代谢调节 代谢调节 代谢调节
- 骨生物学 骨生物学 骨生物学
背景情况:
- 血管与骨质生成和骨质疏松症有关.
- 血管新陈代谢在这些骨疾病中的特定作用尚不清楚.
研究的目的:
- 调查内皮细胞代谢,特别是酸盐激酶M2 (PKM2) 在骨质生成和骨质疏松症中的作用.
- 阐明将血管新陈代谢与骨健康联系起来的分子机制.
主要方法:
- 卵巢切除的小鼠模型具有内皮细胞特异性的Pkm2缺失.
- 进行CUT&Tag和RNA测序分析.
- 在小鼠和骨质疏松症患者的血清代谢.
主要成果:
- 内皮细胞特异性的Pkm2丧失会损害骨质生成,并加剧小鼠的骨质疏松症.
- 在内皮细胞中减少的PKM2降低了血清乳酸,影响了BMSC基因质乳化和骨质基因表达 (COL1A2,COMP,ENPP1,TCF7L2).
- 骨质疏松症患者表现出较低的血清乳酸,减少的基因素乳化和低调的骨质基因在BMSCs.
结论:
- 通过PKM2和乳酸盐生产的内皮细胞糖解对于通过基因组乳化进行BMSC分化和骨形成至关重要.
- 运动和乳酸补充剂可以在缺陷模型中部分恢复骨健康.
- 向内皮细胞代谢为骨质疏松症提供了潜在的治疗策略.
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