通过ETS2/miR-155/STAT1/DNMT1反循环路径,ETS2过度表达改善了骨关节炎中的软骨损伤
Shuxiang Chen1, Xiaotong Zhu2, Wenhuan Ou1
1Department of Orthopaedic, Jiangmen Wuyi Hospital of Traditional Chinese Medicine, Jiangmen, Guangdong, China.
概括
转录因子ETS2在骨关节炎 (OA) 中是下调的. 抑制ETS2通过减少炎症和降解来保护软骨,为OA提供了新的治疗策略.
科学领域:
- 生物化学 生物化学
- 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) 是一种常见的慢性关节疾病,以软骨退化为标志.
- 转录因子失调与OA的发病有关,但机制尚不清楚.
研究的目的:
- 研究转录因子ETS2在骨关节炎中的作用.
- 阐明在OA中ETS2调节和功能背后的分子机制.
主要方法:
- 在OA软骨和软骨细胞中对ETS2表达的分析.
- 在IL-1β诱导的红细胞中进行了体外功能测定 (过度表达和敲击).
- 在体内研究使用DMM诱导的OA小鼠模型.
- 涉及DNMT1,miR-155和STAT1相互作用的机制研究.
主要成果:
- 在OA软骨和IL-1β治疗的肌肉细胞中,ETS2显著下调.
- 过度表达ETS2增强了冠状细胞的增殖,抑制了亡,并减少了炎症和ECM降解.
- 取消ETS2产生了相反的效果.
- 在体内,高调 ETS2 改善了软骨损伤.
- 确定了一个DNMT1/ETS2/miR-155/STAT1反循环,抑制了MAPK信号传递并加剧了OA.
结论:
- 在骨关节炎中,ETS2通过调节状细胞行为和细胞外矩阵恒温起着保护作用.
- 识别的反循环为OA病变发生提供了新的见解.
- ETS2代表了骨关节炎治疗的潜在治疗标.
相关概念视频
The JAK-STAT Signaling Pathway
9.0K
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...
9.0K
TGF - β Signaling Pathway
7.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K
Mesenchymal Stem Cells
4.8K
Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
4.8K


