LIVE IMAGING OF BONE REGENERATION IN ZEBRAFISH

摘要 哺乳动物的骨骼在一生中都有再生的能力，以应对骨折损伤。然而，还有 这种再生潜力的上限，以及在像截肢这样的重大创伤后再生的障碍。 这具有重大的社会经济影响，因为据估计，至少每两个美国人中就有一个在50岁以上 估计每年有150万人患有骨病或有患骨病的风险 由于骨病导致的骨折。我们已经开发了成像方法来研究成骨细胞如何驱动骨骼 斑马鱼的再生，在它们的鳍等骨骼结构严重损伤后表现出强劲的再生能力， 鳞片和下巴。我们的目标是利用这种再生能力，我们创造的新成像平台，以及 斑马鱼可利用的分子遗传学方法来提高我们理解和操纵 骨的再生能力。我们最近发现ERK信号波是一种控制机制 成骨细胞再生。此补充应用程序通过测试假设扩展了我们最初的建议 机械信号通过整合ERK通路的输入信号促进成骨细胞的再生 河马/YAP-Taz通路，另一个在骨形态发生和骨形成中发挥关键作用的信号通路 再生。

ABSTRACT Mammalian bone has the capacity throughout life to regenerate in response to fracture injury. However, there is a ceiling for this regenerative potential, with hurdles to regeneration after a major trauma like limb amputation. This has a significant socio-economic impact, as it is estimated that at least one in two Americans over age 50 is expected to have or be at risk of bone disease, and every year an estimated 1.5 million individuals suffer a fracture due to bone disease. We have developed imaging methods to study how osteoblasts drive bone regeneration in zebrafish, which display robust regeneration after major injury to bony structures like their fins, scales, and jaws. Our goal is to exploit this regenerative capacity, new imaging platforms we have created, and the molecular genetic approaches available in zebrafish to improve our ability to understand and manipulate the regenerative capacity of bone. We have recently identified Erk signaling waves as a mechanism for the control of osteoblast regeneration. This Supplement application extends our original proposal by testing the hypothesis that mechanical signals contribute to osteoblast regeneration by integrating inputs from the Erk pathway and Hippo/Yap-Taz pathway, another signaling pathway playing crucial roles in bone morphogenesis and regeneration.