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Notch 信号过表达诱导斑马鱼骨过度生成。

Overexpression of Notch Signaling Induces Hyperosteogeny in Zebrafish.

机构信息

Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan.

Department of Biological Science & Technology College of Medicine, I-Shou University, Kaohsiung 84001, Taiwan.

出版信息

Int J Mol Sci. 2019 Jul 24;20(15):3613. doi: 10.3390/ijms20153613.

DOI:10.3390/ijms20153613
PMID:31344827
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6696610/
Abstract

Notch signaling is one of the evolutionarily conserved signaling pathways in multicellular organisms. It plays an important role in embryonic development. During skeletal development of vertebrates, it regulates bone homeostasis by manipulating both osteoblastogenesis and osteoclastogenesis through different mechanisms. However, due to the different nature of Notch signaling in mesenchymal stem cell and osteoblast, regulation of Notch signaling in bone-related diseases remains unsettled. Previous studies by cell culture and mouse models showed contradictory results regarding the role of Notch signaling in bone homeostasis. To clarify the role of Notch signaling in osteogenesis, we established a zebrafish model, in which Notch1a intracellular domain (N1aICD) was specifically expressed in the osteoblasts. We found that overexpression of N1aICD in osteoblasts caused hyperosteogeny in the column region of zebrafish with the morphology of narrowed neural/hemal canals. Moreover, increased metabolic activity of osteoblasts instead of augmenting osteoblast number led to hyperosteogeny in N1aICD-overexpressed zebrafish. In summary, we successfully established a transgenic zebrafish line overexpressing N1aICD to clarify the in-vivo function of Notch signaling during osteoblastogenesis. In the future, this fish line can serve as a valuable tool to test the therapeutic drugs for hyperosteogeny.

摘要

Notch 信号通路是多细胞生物中进化保守的信号通路之一。它在胚胎发育中起着重要作用。在脊椎动物的骨骼发育过程中，它通过不同的机制调节成骨细胞和破骨细胞的生成，从而维持骨骼的稳态。然而，由于 Notch 信号在间充质干细胞和成骨细胞中的性质不同， Notch 信号在与骨骼相关的疾病中的调控仍未得到解决。先前的细胞培养和小鼠模型研究表明， Notch 信号在骨骼稳态中的作用存在矛盾的结果。为了阐明 Notch 信号在成骨中的作用，我们建立了一个斑马鱼模型，在该模型中 Notch1a 胞内域（N1aICD）特异性地在成骨细胞中表达。我们发现，成骨细胞中 N1aICD 的过表达导致斑马鱼柱状区的过度骨化，表现为神经/脉管狭窄的形态。此外，成骨细胞代谢活性的增加而不是成骨细胞数量的增加导致 N1aICD 过表达的斑马鱼发生过度骨化。总之，我们成功建立了一种过表达 N1aICD 的转基因斑马鱼系，以阐明 Notch 信号在成骨细胞发生过程中的体内功能。将来，这条鱼线可以作为一种有价值的工具，用于测试治疗过度骨化的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25df/6696610/d15634e8645d/ijms-20-03613-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25df/6696610/59dcf2ff03a3/ijms-20-03613-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25df/6696610/021124e57805/ijms-20-03613-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25df/6696610/a4cfaaf1c545/ijms-20-03613-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25df/6696610/d15634e8645d/ijms-20-03613-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25df/6696610/dccf4f879cf3/ijms-20-03613-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25df/6696610/cab647583bd0/ijms-20-03613-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25df/6696610/ca166d657299/ijms-20-03613-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25df/6696610/62da833caa04/ijms-20-03613-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25df/6696610/49f554a442a4/ijms-20-03613-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25df/6696610/205c87a0a6da/ijms-20-03613-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25df/6696610/59dcf2ff03a3/ijms-20-03613-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25df/6696610/021124e57805/ijms-20-03613-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25df/6696610/a4cfaaf1c545/ijms-20-03613-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25df/6696610/d15634e8645d/ijms-20-03613-g009.jpg

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