Osteoblast differentiation is a key process for bone homeostasis and repair. Multiple signalling pathways have been associated with osteoblast differentiation, yet much remains unknown on how this process is regulated in vivo Previous studies have proposed that the Hippo pathway transcriptional co-activators YAP and TAZ (also known as YAP1 and WWTR1, respectively) maintain progenitor stemness and inhibit terminal differentiation of osteoblasts, whereas others suggest they potentiate osteoblast differentiation and bone formation. Here, we use zebrafish caudal fin regeneration as a model to clarify how the Hippo pathway regulates de novo bone formation and osteoblast differentiation. We demonstrate that Yap inhibition leads to accumulation of osteoprogenitors and prevents osteoblast differentiation in a cell non-autonomous manner. This effect correlates with a severe impairment of Bmp signalling in osteoblasts, likely by suppressing the expression of the ligand bmp2a in the surrounding mesenchymal cells. Overall, our findings provide a new mechanism of bone formation through the Hippo-Yap pathway, integrating Yap in the signalling cascade that governs osteoprogenitor maintenance and subsequent differentiation during zebrafish caudal fin regeneration.

中文翻译：

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Yap通过调节斑马鱼尾鳍再生期间的Bmp信号传导来诱导成骨细胞分化。

成骨细胞分化是骨稳态和修复的关键过程。多种信号传导途径与成骨细胞分化有关，但在体内如何调节该过程方面尚不清楚，以前的研究已经提出，河马途径的转录共激活因子YAP和TAZ（分别称为YAP1和WWTR1）保持祖细胞的干性。并抑制成骨细胞的终末分化，而其他研究则表明它们可增强成骨细胞的分化和骨形成。在这里，我们使用斑马鱼尾鳍再生作为模型来阐明河马通路如何调节从头开始的骨形成和成骨细胞的分化。我们证明Yap抑制导致骨祖细胞的积累，并以非自主方式阻止成骨细胞分化。此作用与成骨细胞中Bmp信号转导的严重损伤有关，可能是通过抑制周围的间充质细胞中配体bmp2a的表达来实现的。总体而言，我们的发现提供了通过Hippo-Yap途径形成骨的新机制，将Yap整合在信号级联中，该信号级联控制着骨祖细胞的维持和斑马鱼尾鳍再生过程中的后续分化。