矩阵刚度通过Piezo1-YAP信号轴调节巨细胞的两极分化
Feng Mei1,2,3, Yaru Guo4, Yu Wang5
1Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cell proliferation
|April 1, 2024
概括
生物材料的刚性会影响巨细胞的行为,影响植入物成功. 用抑制剂向Piezo1-YAP通路促进抗炎反应,增强骨质整合和植入物接受.
科学领域:
- 生物材料科学 生物材料科学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 巨细胞对于生物医学植入物集成至关重要,它们的两极化状态 (促炎M1与抗炎M2) 决定了宿主反应.
- 虽然化学信号在巨细胞极化中的作用是已知的,但物理线索的影响,如基质刚性,对巨细胞功能在植入物骨接口的作用是不太了解的.
研究的目的:
- 研究物理线索,特别是基质刚度,如何调节巨细胞极化.
- 为了阐明涉及度介导的巨细胞两极化所涉及的底层机械传导途径.
- 探索调节巨细胞极化以改善植入物骨整合的潜力.
主要方法:
- 在不同硬度的聚烯胺凝上培养骨髓衍生巨细胞 (BMDM).
- 使用表型标记器评估巨细胞极化状态 (M1/M2).
- 在对矩阵刚性的反应中量化Piezo1表达和YAP激活.
- 利用YAP抑制剂在体外和植入部位微环境中调节巨细胞极化.
主要成果:
- 在硬基质上培养的BMDM采用了亲炎性M1表型,而柔软/中等硬度促进了抗炎M2表型.
- 矩阵硬化提高了Piezo1表达的调节,并通过YAP激活了机械转导通路,有利于M1极化.
- 抑制YAP成功地在植入物微环境中诱导了M2极化,从而提高了骨质整合.
结论:
- Piezo1-YAP信号轴对于机械感知和度介导的巨细胞两极分化至关重要.
- 基质刚度显著影响巨细胞表型,影响植入物骨整合.
- 准Piezo1-YAP通路为设计免疫调节生物材料提供了一种策略,以提高植入物性能.
相关概念视频
01:20The JAK-STAT Signaling Pathway
8.9K
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...
8.9K
01:21Cell Polarization by Rho Proteins
2.7K
Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
2.7K
01:32Cytoskeletal Coordination in Cell Migration
4.8K
A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
4.8K
01:23Role 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