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Mature osteoblasts dedifferentiate in response to traumatic bone injury in the zebrafish fin and skull

机译:成熟的成骨细胞在斑马鱼鳍和颅骨的外伤性骨损伤中脱分化

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摘要

Zebrafish have an unlimited capacity to regenerate bone after fin amputation. In this process, mature osteoblasts dedifferentiate to osteogenic precursor cells and thus represent an important source of newly forming bone. By contrast, differentiated osteoblasts do not appear to contribute to repair of bone injuries in mammals; rather, osteoblasts form anew from mesenchymal stem cells. This raises the question whether osteoblast dedifferentiation is specific to appendage regeneration, a special feature of the lepidotrichia bone of the fish fin, or a process found more generally in fish bone. Here, we show that dedifferentiation of mature osteoblasts is not restricted to fin regeneration afteramputation, but also occurs during repair of zebrafish fin fractures and skull injuries. In both models, mature osteoblasts surrounding the injury downregulate the expression of differentiation markers, upregulate markers of the pre-osteoblast state and become proliferative. Making use of photoconvertible Kaede protein as well as Cre-driven genetic fate mapping, we show that osteoblasts migrate to the site of injury to replace damaged tissue. Our findings suggest a fundamental role for osteoblast dedifferentiation in reparative bone formation in fish and indicate that adult fish osteoblasts display elevated cellular plasticity compared with mammalian bone-forming cells.
机译:断肢后,斑马鱼具有无限的骨骼再生能力。在这个过程中,成熟的成骨细胞向成骨前体细胞去分化,因此代表了新形成的骨的重要来源。相比之下,分化的成骨细胞似乎没有促进哺乳动物骨骼损伤的修复。相反,成骨细胞由间充质干细胞重新形成。这就提出了一个问题,即成骨细胞去分化是特定于附肢再生,鱼鳍鳞翅目鱼类的特殊特征还是鱼骨中普遍存在的过程。在这里,我们显示成熟的成骨细胞去分化不仅限于截肢后的鳍再生,而且还发生在斑马鱼鳍骨折和颅骨损伤的修复过程中。在这两种模型中,围绕损伤的成熟成骨细胞下调分化标志物的表达,上调成骨细胞前状态的标志物并增殖。利用光可转换的Kaede蛋白以及Cre驱动的遗传命运图谱,我们显示成骨细胞迁移到损伤部位以替换受损的组织。我们的研究结果表明成骨细胞去分化在鱼的修复性骨形成中的基本作用,并表明成年鱼成骨细胞与哺乳动物的成骨细胞相比具有更高的细胞可塑性。

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