由c-Fos控制的代谢重新连接控制了骨关节炎中的软骨完整性
Kazuhiko Matsuoka1,2, Latifa Bakiri3, Martin Bilban4,5
1Genes and Disease group, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Annals of the rheumatic diseases
|June 21, 2023
概括
转录因子c-Fos对于骨关节炎 (OA) 中的软骨细胞功能至关重要. 准c-Fos调节的细胞代谢为OA提供了一个潜在的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 已知转录因子激活蛋白-1 (AP-1) 组成部分c-Fos调节了冠状细胞的增殖和分化.
- 它在骨关节炎 (OA) 发病过程中的特定作用在功能上仍未得到评估.
研究的目的:
- 功能性地评估c-Fos在骨关节炎 (OA) 的参与.
- 为了研究c-Fos在调节OA进展期间的冠状细胞生物能量和新陈代谢中的作用.
主要方法:
- 免疫组织化学用于评估人类和小鼠OA软骨中的c-Fos表达.
- 生产了软骨特异性c-Fos淘汰 (c-FosΔCh) 鼠标,并对OA的中间半月体 (DMM) 模型进行了破坏稳定.
- 进行了基因组学,RNA测序 (RNA-seq),qRT-PCR和现场代谢酶试验.
主要成果:
- 在OA软骨中观察到FOS阳性细胞的增加.
- 在c-FosΔCh小鼠中,DMM诱导的软骨破坏恶化,软骨细胞增殖减少,软骨基质减少.
- RNA-seq揭示了转向无氧糖解的转变,减少了pyruvate dehydrogenase (Pdh) 和提高了乳酸脱酶 (Ldh) 的活性.
结论:
- 在对OA的反应中,c-Fos通过平衡糖解和TCA循环之间的pyruvate流量来调节状细胞的生物能量,在调节状细胞的生物能量方面发挥着关键作用.
- 这种由c-Fos控制的代谢适应是骨关节炎的新治疗标.
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