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    Up-regulation of FOXD1 by YAP alleviates senescence and osteoarthritis, PLOS Biology, 01 Apr 2019
    2019-03-09 | 【     】【打印】【关闭

    PLOS Biology, 01 April, 2019,DOI:https://doi.org/10.1371/journal.pbio.3000201

    Up-regulation of FOXD1 by YAP alleviates senescence and osteoarthritis

    Lina Fu , Yuqiong Hu , Moshi Song, Zunpeng Liu, Weiqi Zhang, Fa-Xing Yu, Jun Wu, Si Wang, Juan Carlos Izpisua Belmonte, Piu Chan, Jing Qu , Fuchou Tang , Guang-Hui Liu

    Abstract

    Cellular senescence is a driver of various aging-associated disorders, including osteoarthritis. Here, we identified a critical role for Yes-associated protein (YAP), a major effector of Hippo signaling, in maintaining a younger state of human mesenchymal stem cells (hMSCs) and ameliorating osteoarthritis in mice. Targeted knockout (KO) of YAP in hMSCs resulted in premature cellular senescence. Mechanistically, YAP cooperated with TEA domain transcriptional factor (TEAD) to activate the expression of forkhead box D1 (FOXD1), a geroprotective protein. YAP deficiency led to the down-regulation of FOXD1. In turn, overexpression of YAP or FOXD1 rejuvenated aged hMSCs. Moreover, intra-articular administration of lentiviral vector encoding YAP or FOXD1 attenuated the development of osteoarthritis in mice. Collectively, our findings reveal YAP–FOXD1, a novel aging-associated regulatory axis, as a potential therapeutic target for gene therapy to alleviate osteoarthritis.

    文章链接:https://journals.plos.org/plosbiology/article/authors?id=10.1371/journal.pbio.3000201

    相关报道:http://www.yt-chuanpeng.com/kyjz/zxdt/201904/t20190402_5265617.html

     

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