YAP1 regulates chondrogenic differentiation of ATDC5 promoted by temporary TNF-α stimulation through AMPK signaling pathway
YAP1 regulates chondrogenic differentiation of ATDC5 promoted by temporary TNF-α stimulation through AMPK signaling pathway
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YAP1 通过 AMPK 信号通路调节临时 TNF-α 刺激促进的 ATDC5 软骨分化
DOI：
10.1007/s11010-020-03846-z
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发表时间：
2020-08-03
影响因子：
4.3
通讯作者：
Wang, Jiawei
中科院分区：
文献类型：
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作者：
Chen, Peiyu;Yang, Beining;Wang, Jiawei
据报道，在小鼠模型中，炎症反应早期在骨折部位局部注射肿瘤坏死因子- α (tnf - α)可改善骨折修复。然而，潜在的机制尚不清楚。软骨内成骨是一个与骨折修复高度相关的过程，需要一定量的软骨细胞肥大。本研究旨在探讨tnf - α对小鼠软骨性ATDC5细胞分化的影响及其机制。在这项研究中，通过短暂的tnf - α刺激可以改善ATDC5细胞的软骨分化。此外，在短暂的tnf - α刺激后，yes相关蛋白1 （YAP1）的表达被抑制。由tnf - α触发的ATDC5细胞中炎症介质和软骨增生相关基因的表达在YAP1过表达组受到抑制，而在YAP1敲低组得到增强。从机制上讲，tnf - α诱导的5MODIFIER LETTER PRIME amp活化蛋白激酶（AMPK）信号通路的激活受YAP1的调控，这是由YAP1过表达组和敲低组中磷酸化的AMPK/AMPK变化比率所揭示的。此外，tnf - α增强软骨分化的潜力可能被AMPK抑制剂部分逆转。综上所述，我们首次证明YAP1部分通过AMPK信号调节tnf - α增强软骨细胞分化的能力。
Local injection of tumor necrosis factor-alpha (TNF-alpha) at bone fracture sites during the early stage of the inflammatory response is reported to improve fracture repair in a murine model. However, the underlying mechanism is unclear. Endochondral bone formation, a process that is highly related to fracture repair, requires a certain amount of chondrocyte hypertrophy. This study aimed to investigate the effect of TNF-alpha on the differentiation of murine chondrogenic ATDC5 cells and the underlying mechanism. In this study, improved chondrogenic differentiation of ATDC5 cells was achieved by brief TNF-alpha stimulation. Moreover, the expression of Yes-associated protein 1 (YAP1) was suppressed after brief TNF-alpha stimulation. The expressions of inflammatory mediators and chondrogenic and hypertrophic-associated genes in ATDC5 cells triggered by TNF-alpha were suppressed in the YAP1 overexpression group but enhanced in the YAP1 knockdown group. Mechanistically, TNF-alpha-induced activation of the 5MODIFIER LETTER PRIME AMP-activated protein kinase (AMPK) signaling pathway was regulated by YAP1, as revealed by the phosphorylated-AMPK/AMPK change ratios in the YAP1 overexpression and knockdown groups, respectively. Moreover, the potential for TNF-alpha to enhance chondrogenic differentiation could be partially reversed with an AMPK inhibitor. Taken together, we demonstrate, for the first time, that YAP1 modulates the ability of TNF-alpha to enhance chondrocyte differentiation partly through AMPK signaling.