Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
J Orthop Res. 2012 Feb;30(2):296-303. doi: 10.1002/jor.21518. Epub 2011 Aug 4.
Previous studies have demonstrated that Notch signaling regulates endochondral and intramembranous bone formation by controlling cell proliferation and differentiation. Notch signaling has also been shown to regulate healing in a variety of tissues. The objective of this study was to characterize and compare activation of the Notch signaling pathway during endochondral and intramembranous bone healing using tibial fracture and calvarial defect injury models, respectively. Bilateral tibial fractures or bilateral 1.5 mm diameter calvarial defects were created in mice, and tissues were harvested at 0, 5, 10, and 20 days post-fracture. Gene expression of Notch signaling components was upregulated during both tibial fracture and calvarial defect healing, with expression generally higher during tibial fracture healing. The most highly expressed ligand and receptor during healing, Jag1 and Notch2 (specifically the activated receptor, known as NICD2), were similarly localized in mesenchymal cells during both modes of healing, with expression decreasing during chondrogenesis, but remaining present in osteoblasts at all stages of maturity. Results suggest that in addition to embryological bone development, Notch signaling regulates both endochondral and intramembranous bone healing.
先前的研究表明，Notch 信号通路通过控制细胞增殖和分化来调节软骨内和膜内骨的形成。Notch 信号通路还被证明可以调节多种组织的愈合。本研究的目的是使用胫骨骨折和颅骨缺损损伤模型分别对软骨内和膜内骨愈合过程中 Notch 信号通路的激活进行特征描述和比较。在小鼠中建立双侧胫骨骨折或双侧 1.5 毫米直径颅骨缺损，在骨折后 0、5、10 和 20 天采集组织。Notch 信号通路成分的基因表达在胫骨骨折和颅骨缺损愈合过程中均上调，在胫骨骨折愈合过程中表达通常更高。在愈合过程中，表达最高的配体和受体 Jag1 和 Notch2（特别是激活受体，称为 NICD2）在两种愈合方式中均在间充质细胞中具有相似的定位，在软骨生成过程中表达减少，但在成骨细胞的所有成熟阶段仍然存在。结果表明，Notch 信号通路除了在胚胎骨骼发育中起作用外，还调节软骨内和膜内骨的愈合。
