拉伸应力激活和外体转移的YAP/TAZ-Notch电路指定了H型内皮细胞用于细分骨再生
Feng Wang1, Shanyu Li1, Lingchi Kong1
1Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|January 16, 2024
概括
伊利扎罗夫技术使用拉伸应力通过激活H型内皮细胞 (THECs) 来再生骨. 这个过程建立了一个YAP/TAZ-Notch电路,促进骨愈合,并提供新的治疗策略.
科学领域:
- 生物医学工程 生物医学工程
- 再生医学是一种再生医学.
- 整形外科手术 整形外科手术
背景情况:
- 伊利扎罗夫技术创新拉伸应力 (TS) 用于骨再生,但通过H型内皮细胞 (THEC) 合血管生成和骨质生成的机制尚不清楚.
- 分心骨质生成 (DO) 对于骨重建至关重要,但它的细胞和分子基础需要进一步阐明.
研究的目的:
- 调查THECs在分散骨质生成 (DO) 期间TS诱导的骨再生中的作用.
- 阐明分子机制,包括YAP/TAZ-Notch电路,控制THEC激活和TS下的骨形成.
- 探索由TS刺激的内皮细胞衍生的外体的治疗潜力,以治疗骨缺陷.
主要方法:
- 利用Ilizarov技术,将拉力应力 (TS) 应用于骨髓内皮细胞 (BMECs).
- 研究了与PDZ结合动机 (TAZ) 途径的yes相关蛋白 (YAP) /转录辅助激活剂的激活及其对Notch信号的调节.
- 分析了Notch1和Delta样联体4在THEC表型和功能中的作用.
- 由TS刺激的BMECs分泌的特征外体因其在骨再生中的治疗潜力而显著.
主要成果:
- 证明Ilizarov技术通过THECs诱导一种类似于代谢的架构,促进细分骨再生.
- 确定TS激活YAP/TAZ,这可以调节Notch1和Delta样联体4的升级,从而促进THEC表型.
- 建立了一个正反循环 (YAP/TAZ-Notch电路),其中Notch信号增强了YAP/TAZ活动.
- 展示了TS刺激的BMEC衍生的外体促进骨缺陷愈合,模仿伊利扎罗夫技术的效果.
结论:
- 伊利扎罗夫技术通过诱导THEC形成和激活YAP/TAZ-Notch电路来驱动细分骨再生.
- 由TS刺激的内皮细胞衍生的外体对增强骨缺陷愈合有希望.
- 这些发现为针对THEC用于骨重建的新生物疗法提供了基础.
相关概念视频
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
01:16TGF - β Signaling Pathway
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 are of three kinds RI, RII, and RIII. The RI...
01:13Cell-matrix's Response to Mechanical Forces
In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue.
Anchoring junctions mechanically attach a cell to the...
Anchoring junctions mechanically attach a cell to the...
01:26Tension Response at Adherens Junctions
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains...