矩阵刚度通过由线粒体损伤引起的H3K27me3脱甲基化加剧了骨关节炎的进展
Tianyou Kan1,2, Hanjun Li3, Lingli Hou4
1Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
iScience
|August 19, 2024
概括
软骨上的异常机械负荷通过线粒体改变了状细胞表观遗传,导致骨关节炎 (OA). 增加的矩阵刚度和线粒体损伤促进H3K27me3脱甲基化,驱动OA的发病.
科学领域:
- 生物医学工程 生物医学工程
- 分子生物学分子生物学
- 类风湿病学 类风湿病学
背景情况:
- 骨关节炎 (OA) 的发病包括异常的表观遗传学和对软骨细胞的机械负荷.
- 连接机械负荷与状细胞表观遗传变化的精确机制在很大程度上是未知的.
- 细胞外基质 (ECM) 和线粒体参与调解细胞对机械刺激的反应.
研究的目的:
- 研究异常机械负荷如何通过OA的线粒体通路影响状细胞表观遗传.
- 阐明矩阵力学和线粒体功能的作用在调节OA发育期间的状细胞表观遗传学.
主要方法:
- 在OA中对软骨矩阵刚度和状细胞线粒体完整性的分析.
- 在不同的机械条件下评估H3K27me3脱甲基化在红细胞中.
- 研究线粒体透性过渡孔 (mPTP) 开放和Phf8转位.
主要成果:
- 甲状腺癌软骨表现出增加的矩阵刚性和严重的状细胞线粒体损伤.
- 在对矩阵刚度增加的反应中观察到氏体H3K27me3脱甲基化.
- mPTP 开放促进了 Phf8 核转位,催化了 H3K27me3 脱甲基化.
结论:
- 软骨矩阵机制通过线粒体调节状细胞表观遗传学,有助于OA.
- 线粒体功能障碍和Phf8介导的H3K27me3脱甲基化是OA机械生物学中的关键机制.
- 这项研究为OA病变发生提供了新的机械生物学视角.
相关概念视频
Mitochondrial Membranes
9.4K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
9.4K
Mitochondria
11.7K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
11.7K


