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NF-κB Signaling Negatively Regulates Osteoblast Dedifferentiation during Zebrafish Bone Regeneration.
Developmental Cell ( IF 10.7 ) Pub Date : 2019-12-13 , DOI: 10.1016/j.devcel.2019.11.016 Rashmi Mishra 1 , Ivonne Sehring 1 , Maria Cederlund 1 , Medhanie Mulaw 2 , Gilbert Weidinger 1
Developmental Cell ( IF 10.7 ) Pub Date : 2019-12-13 , DOI: 10.1016/j.devcel.2019.11.016 Rashmi Mishra 1 , Ivonne Sehring 1 , Maria Cederlund 1 , Medhanie Mulaw 2 , Gilbert Weidinger 1
Affiliation
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Dedifferentiation of mature cells is an intriguing cellular process associated with regeneration of several organs. During zebrafish fin regeneration, osteoblasts dedifferentiate to osteogenic progenitors that provide source cells for bone restoration. We performed a high-content in vivo chemical screen for regulators of osteoblast dedifferentiation and fin regenerative growth. NF-κB signaling emerged as a specific regulator of dedifferentiation. The pathway is active in mature osteoblasts and downregulated prior to dedifferentiation. Pathway activation blocked osteoblast dedifferentiation, while NF-κB signaling inhibition enhanced dedifferentiation. Conditional Cre-lox-mediated NF-κB signaling manipulation specifically in osteoblasts showed that the pathway acts cell autonomously to interfere with osteoblast dedifferentiation. NF-κB signaling acts upstream of retinoic acid (RA) signaling, which also needs to be downregulated for dedifferentiation to occur, via suppression of the RA-degrading enzyme cyp26b1. Our findings shed light on the molecular regulation of regenerative cellular plasticity.
中文翻译：
NF-κB信号负调控斑马鱼骨再生过程中成骨细胞的去分化。
成熟细胞的去分化是与几个器官再生相关的有趣的细胞过程。在斑马鱼鳍再生期间，成骨细胞分化为成骨祖细胞，后者为骨修复提供了源细胞。我们对成骨细胞去分化和鳍再生生长的调节剂进行了高含量的体内化学筛选。NF-κB信号作为去分化的特定调节剂出现。该途径在成熟的成骨细胞中活跃，并在去分化前下调。通路激活阻止了成骨细胞的去分化，而NF-κB信号传导的抑制作用增强了去分化。有条件的Cre-lox介导的NF-κB信号转导特别是在成骨细胞中显示，该途径可自主作用于细胞，从而干扰成骨细胞的去分化。NF-κB信号在视黄酸（RA）信号的上游起作用，通过抑制RA降解酶cyp26b1，它也需要下调以进行去分化。我们的发现揭示了再生细胞可塑性的分子调控。
更新日期：2019-12-19
中文翻译：
NF-κB信号负调控斑马鱼骨再生过程中成骨细胞的去分化。
成熟细胞的去分化是与几个器官再生相关的有趣的细胞过程。在斑马鱼鳍再生期间，成骨细胞分化为成骨祖细胞，后者为骨修复提供了源细胞。我们对成骨细胞去分化和鳍再生生长的调节剂进行了高含量的体内化学筛选。NF-κB信号作为去分化的特定调节剂出现。该途径在成熟的成骨细胞中活跃，并在去分化前下调。通路激活阻止了成骨细胞的去分化，而NF-κB信号传导的抑制作用增强了去分化。有条件的Cre-lox介导的NF-κB信号转导特别是在成骨细胞中显示，该途径可自主作用于细胞，从而干扰成骨细胞的去分化。NF-κB信号在视黄酸（RA）信号的上游起作用，通过抑制RA降解酶cyp26b1，它也需要下调以进行去分化。我们的发现揭示了再生细胞可塑性的分子调控。
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