激活转录因子4和中白素6之间的相互作用决定了骨质细胞的分化和活动
Shasha Tu1, Sijun Liu1, Mengmeng Duan2
1Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China.
概括
激活转录因子4 (Atf4) 直接结合介素6 (IL6) 促进体,驱动骨质细胞形成. 这种Atf4-IL6通路影响骨质平衡,并为骨质疏松症治疗提供了洞察力.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 骨生物学 骨生物学 骨生物学
背景情况:
- 骨质细胞的功能对于骨稳定,修复和重塑至关重要.
- 骨质细胞生成是由转录因子和细胞因子调节的,但Atf4和IL6之间的相互作用仍然不清楚.
研究的目的:
- 研究Atf4和IL6在骨质细胞分化和活动中的相互作用.
- 阐明Atf4介导的骨质细胞生成背后的分子机制.
主要方法:
- 使用lentiviral过度表达和siRNA转染来操纵Atf4水平.
- 染色体免疫沉 (ChIP) 试验被用于评估Atf4与IL6促进体的结合.
- 分析了骨质细胞标记物的表达和信号通路的激活.
主要成果:
- 在ATF4过度表达上调关键骨质细胞标志物 (Nfatc1,c-Fos,Dcst1,Mmp2/9,cathepsin K).
- Atf4直接与IL6促进体结合,表明IL6的转录调节由Atf4.
- Atf4-IL6轴激活了Jak1/Stat3信号,促进了大型多核骨质细胞的形成.
结论:
- 一个新的Atf4-IL6信号轴显著促进骨质细胞分化,独立于正规的MCSF和RANKL通路.
- 这一发现突显了骨质细胞形成的复杂调节机制.
- 了解这种途径可以了解骨质疏松性疾病和潜在的治疗策略.
相关概念视频
Master Transcription Regulators
7.6K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.6K
TGF - β Signaling Pathway
10.4K
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...
10.4K
Osteoclasts in Bone Remodeling
3.8K
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...
3.8K
NF-κB-dependent Signaling Pathway
9.7K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
9.7K
T Cell Types and Functions
2.1K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
2.1K
The JAK-STAT Signaling Pathway
11.8K
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...
11.8K


