在炎症期间,巨细胞和MSC中的糖溶性重编程
Xueping Li1, Huaishuang Shen1,2, Mao Zhang3
1Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, United States.
Frontiers in immunology
|September 7, 2023
概括
由受污染的聚乙烯颗粒引起的炎症会损害骨细胞的能量产生,将巨细胞和介质细胞向糖解转移,远离线粒体功能. 这种代谢转变可能会阻碍骨愈合和免疫反应.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 失调的炎症与骨疾病,如骨关节炎和非工会有关.
- 污染的聚乙烯颗粒 (cPE) 诱导长时间的炎症并损害骨形成.
- 细胞生物能学和线粒体在骨炎中的功能仍然不太清楚.
研究的目的:
- 在cPE诱导的炎症条件下,研究巨细胞 (Mφ) 和介酶体 stromal 细胞 (MSCs) 中的代谢和生物能量重编程.
- 为了确定糖溶性重编程和线粒体功能障碍是否会导致免疫调节和骨再生受损.
主要方法:
- 使用海马XF96分析仪评估线粒体呼吸 (氧气消耗率) 和糖解 (细胞外酸化率) 在暴露于cPE的Mφ和MSC中.
- 采用实时qPCR分析关键代谢酶和炎症标记物的基因表达.
- 从氧化酸化 (OXPHOS) 和糖解中量化实时ATP生产率.
主要成果:
- 暴露于cPE的Mφ显著降低了氧化酸化和增加了糖解,更依赖糖性ATP (glycoATP).
- MSCs显示增强了糖解,但氧气消耗率没有显著变化,具有高的glycoATP.
- 暴露于cPE的Mφ和MSC都显示出高调 glycolytic 调节器,Mφ显示出增强的促炎细胞因子表达.
结论:
- 暴露于cPE会诱导骨髓衍生的Mφ和MSC中的功能失调的生物能活性,可能会损害骨内的免疫调节功能.
- 混乱的线粒体功能和代谢重编程是解决骨疾病炎症的潜在治疗点.
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