通过WNT4/NF-κB通路,BRD4促进了人类骨髓中酶干细胞的骨质基因分化
Tao Ning1,2, Huihui Guo2, Mingming Ma2
1Department of Bone and Joint Surgery, The First Affiliated Hospital of Jinan University, Guangzhou City, 510630, Guangdong Province, People's Republic of China.
Journal of orthopaedic surgery and research
|November 19, 2023
概括
含基因的蛋白4 (BRD4) 通过增强WNT4表达和抑制NF-κB通路来促进骨的形成. 这一发现为骨质疏松症治疗策略提供了新的见解.
科学领域:
- 干细胞生物学 干细胞生物学
- 分子生物学分子生物学
- 代谢途径 代谢途径
背景情况:
- 人类骨髓介质干细胞 (hBMSCs) 对于骨形成至关重要,并与骨质疏松症有关.
- 含有原体的蛋白4 (BRD4) 被认为是骨质原体分化的关键调节者.
研究的目的:
- 研究BRD4在hBMSCs骨质性分化中的作用和机制.
- 在这个过程中探索BRD4,WNT4和NF-κB通路之间的关系.
主要方法:
- 通过流细胞计,ALP测定和阿利沙林红色染色来评估骨质分化.
- 分析了通过西部斑块和qPCR的蛋白质和基因表达 (BRD4,WNT4,NF-κB,糖解标记物).
- 利用代谢学,双化酶记者测定和染色体免疫沉来阐明分子相互作用和代谢变化.
主要成果:
- 在骨质分化过程中,BRD4表达显著增加.
- BRD4敲击破坏了hBMSC的骨质分化,并与改变的葡萄糖代谢有关.
- BRD4直接与WNT4促进体结合,而WNT4/NF-κB信号传导则调解BRD4对分化和糖解的影响.
结论:
- BRD4促进了hBMSC的骨质分化.
- 这种促进通过增强WNT4表达发生,导致NF-κB通路的抑制.
- BRD4对WNT4和NF-κB信号传递的影响对于调节骨形成和葡萄糖代谢至关重要.
相关概念视频
Non-Canonical Wnt Signaling Pathways
7.3K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.3K
Canonical Wnt Signaling Pathway
8.8K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.8K


