YAP通过维持钙稳态和线粒体功能调节鹿茸软骨细胞的肥大和凋亡。

IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Bai-Yu Li , Zhan-Qing Yang , Yin-Fei Xing, Qiao-Ling Zhang, Chen-Hao Wang, Zhan-Peng Yue, Bin Guo
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引用次数: 0

摘要

YAP是软骨形成和软骨内骨形成所必需的,但其对鹿茸软骨细胞肥大和凋亡的影响尚不清楚。本研究发现YAP在鹿角软骨细胞中大量表达。YAP的失活抑制了鹿茸软骨细胞的肥大,促进了软骨细胞的凋亡。进一步的分析表明,YAP的阻断通过增强依赖于YTHDF2的IP3R1/2 mRNA的稳定性来诱导细胞质Ca2+的积累,而YTHDF2已被确定为YAP/TEAD的直接下游靶点。同时,YAP的衰减激活了胞质Ca2+介导的PPP3R1/NFATC通路,然后通过NFATC靶向MCU导致线粒体Ca2+升高。在鹿角软骨细胞中,YAP的失活破坏了线粒体形态,降低了ATP含量,降低了线粒体膜电位,但这些影响被MCU的阻断所中和。此外,抑制YAP可通过打开线粒体通透性过渡孔,促进mtROS从功能失调的线粒体渗漏到细胞质中,导致细胞内ROS积累和脂质过氧化。在YAP失活的情况下,加入ROS清除剂可以挽救鹿角软骨细胞分化缺陷,保护软骨细胞免于凋亡。总的来说,YAP通过维持Ca2+稳态和线粒体功能调节鹿茸软骨细胞的肥大和凋亡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

YAP regulates the hypertrophy and apoptosis of antler chondrocytes through maintaining calcium homeostasis and mitochondrial function

YAP regulates the hypertrophy and apoptosis of antler chondrocytes through maintaining calcium homeostasis and mitochondrial function
YAP is required for chondrogenesis and endochondral bone formation, but its effect on the hypertrophy and apoptosis of antler chondrocytes remains unclear. The present study revealed that YAP was abundantly expressed in antler chondrocytes. Inactivation of YAP restrained the hypertrophy of antler chondrocytes and facilitated chondrocyte apoptosis. Further analysis indicated that blockage of YAP induced the accumulation of cytosolic Ca2+ by enhancing the stability of IP3R1/2 mRNA dependent on YTHDF2, that had been identified as a direct downstream target of YAP/TEAD. Meanwhile, attenuation of YAP activated the cytosolic Ca2+-mediated PPP3R1/NFATC pathway and then brought about the elevation of mitochondrial Ca2+ via NFATC-targeted MCU. In antler chondrocytes, inactivation of YAP disrupted the mitochondrial morphology, diminished the ATP content and lowered the mitochondrial membrane potential, but these effects were neutralized by the blockage of MCU. Moreover, inhibition of YAP promoted the leakage of mtROS from dysfunctional mitochondria into the cytosol through opening the mitochondrial permeability transition pore, resulting in intracellular ROS accumulation and lipid peroxidation. Addition of ROS scavenger rescued the defective differentiation of antler chondrocytes and protected chondrocytes against apoptosis under the context of YAP inactivation. Collectively, YAP regulated the hypertrophy and apoptosis of antler chondrocytes through maintaining Ca2+ homeostasis and mitochondrial function.
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来源期刊
Cellular signalling
Cellular signalling 生物-细胞生物学
CiteScore
8.40
自引率
0.00%
发文量
250
审稿时长
27 days
期刊介绍: Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.
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