Hydrostatic Pressure Modulates Intervertebral Disc Cell Survival and Extracellular Matrix Homeostasis via Regulating Hippo-YAP/TAZ Pathway.
Hydrostatic Pressure Modulates Intervertebral Disc Cell Survival and Extracellular Matrix Homeostasis via Regulating Hippo-YAP/TAZ Pathway.
复制标题
静水压通过调节 Hippo-YAP/TAZ 通路调节椎间盘细胞存活和细胞外基质稳态
DOI：
10.1155/2021/5626487
复制
发表时间：
2021
影响因子：
4.3
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Wang Y;Bai B;Hu Y;Wang H;Liu N;Li Y;Li P;Zhou G;Zhou Q
已有的研究证明，静水压力对椎间盘（IVD）的生物学行为有多种影响。然而，以往的研究结论并不一致，这是由于这些研究中所使用的静水压加载装置和观察方法的差异。本研究旨在利用自行研制的新型静水压力生物反应器，探讨动态静水压力对脊索髓核（NP）和纤维软骨内环（AF）生物学行为的调节作用及其可能机制。通过组织学分析，评价不同静水压下兔IVD组织生物学行为的差异。结果显示，低负荷动态静水压力通过上调N-钙粘蛋白（N-CDH）和整合素β1，有利于脊索NP和纤维软骨内AF的细胞存活和细胞外基质（ECM）稳态。相比之下，高幅度的动态静水压力通过增强Hippo-YAP/TAZ通路介导的细胞凋亡，加剧了NP和内部AF中ECM稳态的破坏。此外，内AF表现出更大的耐受生理中等负荷程度的静水压力比脊索NP。其潜在机制与脊索NP和纤维软骨内AF中机械感受因子的差异表达有关，这影响了静水压力下细胞的命运。我们的研究结果可能会提供更好的理解静水压力的调控作用的细胞命运的承诺和基质代谢的IVD和更实质性的证据，使用静水压力生物反应器在探索IVD的退化机制以及再生策略。
Established studies proved that hydrostatic pressure had multiple effects on the biological behavior of the intervertebral disc (IVD). However, the conclusions of the previous studies were inconsistent, due to the difference in hydrostatic loading devices and observing methods used in these studies. The current study is aimed at investigating the role of dynamic hydrostatic pressure in regulating biological behavior of the notochordal nucleus pulposus (NP) and fibrocartilaginous inner annulus fibrosus (AF) and its possible mechanism using our novel self-developed hydrostatic pressure bioreactor. The differences in the biological behavior of the rabbit IVD tissues under different degree of hydrostatic pressure were evaluated via histological analysis. Results revealed that low-loading dynamic hydrostatic pressure was beneficial for cell survival and extracellular matrix (ECM) homeostasis in notochordal NP and fibrocartilaginous inner AF via upregulating N-cadherin (N-CDH) and integrin β1. In comparison, high-magnitude dynamic hydrostatic pressure aggravated the breakdown of ECM homeostasis in NP and inner AF via enhancing the Hippo-YAP/TAZ pathway-mediated cell apoptosis. Moreover, inner AF exhibited greater tolerance to physiological medium-loading degree of hydrostatic pressure than notochordal NP. The potential mechanism was related to the differential expression of mechanosensing factors in notochordal NP and fibrocartilaginous inner AF, which affects the fate of the cells under hydrostatic pressure. Our findings may provide a better understanding of the regulatory role of hydrostatic pressure on the cellular fate commitment and matrix metabolism of the IVD and more substantial evidence for using hydrostatic pressure bioreactor in exploring the IVD degeneration mechanism as well as regeneration strategies.
登录
查看更多内容
高强度压缩通过p38 MAPK-ROS途径加速髓核细胞的过早衰老
影响因子：
4.9
作者：
Li P;Hou G;Zhang R;Gan Y;Xu Y;Song L;Zhou Q
通讯作者：
Zhou Q
影响因子：
3
作者：
Kim, KW;Lim, TH;An, HS
通讯作者：
An, HS
影响因子：
2.8
作者：
Hirata, Hiroaki;Yurube, Takashi;Nishida, Kotaro
通讯作者：
Nishida, Kotaro
影响因子：
2.8
作者：
Kasra, M;Goel, V;Buckwalter, J
通讯作者：
Buckwalter, J
影响因子：
--
作者：
Le Maitre, Christine Lyn;Frain, Jennie;Hoyland, Judith Alison
通讯作者：
Hoyland, Judith Alison