YAP和TAZ结合了骨质母细胞前体动员到血管生成和机理调节在小鼠骨发育中的机制
Joseph M Collins1, Annemarie Lang1, Cristian Parisi2
1Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA; Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Developmental cell
|December 23, 2023
概括
是的相关蛋白 (YAP) 和TAZ通过将骨质母细胞前体细胞运动与血管生长相结合来调节胚胎骨发育. 这些机械反应调节器对于骨质生成期间的血管侵袭和软骨重塑至关重要.
科学领域:
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 胎儿骨发育涉及生长板中的软骨转化,需要与血管协调骨质母细胞前体的动员.
- 胚胎发育期间骨质母细胞前体细胞动员和机械感应的机制在很大程度上是未知的.
- 成年人骨维护涉及血管相邻的骨质母细胞前体,对机械刺激做出反应.
研究的目的:
- 研究机械反应性转录调节器YAP和TAZ在胚胎骨发育中的作用.
- 为了阐明这些调节器如何控制骨质细胞前体的调动,血管生成和软骨重塑.
- 了解胚胎小鼠骨质生成的机制调节.
主要方法:
- 单细胞RNA测序以识别细胞群.
- 研究YAP和TAZ在小鼠胚胎骨质生成中的功能.
- 3D人类细胞共同培养模型来评估血管生成.
- 对转录程序,原-整合素相互作用和CXCL12信号的分析.
主要成果:
- YAP和TAZ在空间上将骨质母细胞前体动员与血管生成结合起来,并调节血管形态发生.
- 这些调节器控制软骨重塑,并调节胚胎骨质生成的机制调节.
- YAP和TAZ调节与血管相关的骨质母细胞前体,通过原-整蛋白相互作用和CXCL12.2影响血管入侵.
- 在3D共培养中,CXCL12治疗挽救了YAP/TAZ贫的树皮细胞中受损的血管生成.
结论:
- YAP和TAZ是胚胎骨发育的关键调节者,将机械线索与血管化和骨质生成联系起来.
- 与血管相关的骨质母细胞前体在调解血管生成和软骨重塑中发挥着关键作用.
- 这些发现确定了YAP/TAZ和血管相关骨质母细胞前体在骨发育中的新功能.
相关概念视频
Osteoclasts in Bone Remodeling
2.9K
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...
2.9K
Bone Remodeling
38.3K
Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
38.3K
Regulation of Angiogenesis and Blood Supply
2.6K
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...
2.6K
Role of Matrix Metalloproteases in Degradation of ECM
2.4K
Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
2.4K
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


