在椎间盘退化中HDAC9的分子机制和治疗潜力
Ming Lei1, Hui Lin2, Deyao Shi2
1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China. leiming2010@hust.edu.cn.
Cellular & molecular biology letters
|December 13, 2023
概括
基斯脱乙酶9 (HDAC9) 保护核细胞免受退化和亡,这表明它是椎间盘退化 (IVDD) 的潜在治疗标.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 再生医学是一种再生医学.
背景情况:
- 椎间盘退化 (IVDD) 是腰部疼痛的主要原因.
- 生物信息学分析显示,在退行性核脉 (NP) 样本中,Histone deacetylase 9 (HDAC9) 的降低.
- 在IVDD进展中HDAC9的作用需要研究.
研究的目的:
- 研究HDAC9在IVDD的发展和进展中的作用.
- 探索HDAC9作为IVDD治疗点的潜力.
主要方法:
- 使用HDAC9淘汰和过度表达的小鼠模型.
- 通过MRI和组织学分析评估IVDD的进展.
- 在试验室中研究了NP细胞亡和活力.
- 采用mRNA-seq和co-IP/MS来识别HDAC9受调节的因素,包括RUNX3.3.
主要成果:
- 在HDAC9淘汰赛中的小鼠中,自发发育了与年龄相关的IVDD.
- 在小鼠模型中,HDAC9过度表达减轻了IVDD症状.
- HDAC9沉默降低了NP细胞活力和增加了细胞亡;过度表达具有相反的效果.
- HDAC9脱乙基化并稳定RUNX3,而RUNX3的倒置逆转了HDAC9的沉默效应.
结论:
- 在IVDD期间,HDAC9在保护NP细胞免受亡和生命能力丧失方面发挥着至关重要的作用.
- HDAC9抑制RUNX3的乙化和表达,从而减轻IVDD的进展.
- HDAC9代表了治疗IVDD的潜在治疗标.
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