骨关节炎中的表观遗传学:新兴的机械和翻译景观
Yaniet T Ghezai1, Nada M Farhat1, Saleh M S Ibrahim2,3
1Department of Biological Sciences, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates.
Connective tissue research
|July 12, 2025
概括
基因表观机制,如DNA甲基化和基因素修饰,显著影响骨关节炎 (OA) 的进展. 针对这些表观遗传因素在临床前的OA模型中显示出治疗前景,尽管临床翻译面临挑战.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 类风湿病学 类风湿病学
背景情况:
- 表观遗传机制在调节关键的骨关节炎 (OA) 病变的基因表达方面发挥着至关重要的作用.
- 了解这些表观遗传变化是开发OA新型治疗策略的关键.
研究的目的:
- 审查过去25年对OA的主要表观遗传学研究,重点关注机制和治疗潜力.
- 要突出DNA甲基化,基因组修饰和非编码RNAs (ncRNAs) 在OA中的作用.
主要方法:
- 在OA小鼠模型中调查表观遗传机制的临床前研究的全面审查.
- 对DNA甲基转移酶,基因组修饰酶 (例如EZH2,DOT1L,PCAF,BRD4,HDAC1/2) 和ncRNAs (miRNAs,circRNAs,lncRNAs) 在OA中的研究进行分析.
主要成果:
- 基因甲基化,基因素修饰 (乙化,甲基化) 和ncRNAs是OA相关基因表达的关键调节者.
- 向像DNA甲基转移酶,EZH2,DOT1L,PCAF,BRD4和HDACs这样的表观遗传酶在临床前OA模型中显示出治疗潜力.
- 特定的miRNAs,circRNAs和lncRNAs被确定为软骨稳态和OA病变的重要调节者.
结论:
- 表观遗传机制为骨关节炎提供了有希望的治疗点,临床前研究表明潜在的益处.
- 临床翻译受到表观遗传调节的复杂性,患者异质性和特定环境的改变的阻碍.
- 未来的研究应该专注于确定临床表观遗传标记物和开发选择性表观遗传调节器,用于治疗OA.
相关概念视频
01:46Epigenetic Regulation
31.4K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
31.4K
01:11Genome-wide Association Studies-GWAS
14.3K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
14.3K
01:20The JAK-STAT Signaling Pathway
9.3K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
9.3K
01:31Osteoclasts in Bone Remodeling
3.2K
Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
3.2K
02:25Spreading of Chromatin Modifications
8.5K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.5K