Notch signaling components are upregulated during both endochondral and intramembranous bone regeneration
Notch signaling components are upregulated during both endochondral and intramembranous bone regeneration
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DOI：
10.1002/jor.21518
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发表时间：
2012-02-01
影响因子：
2.8
通讯作者：
Hankenson, Kurt D.
中科院分区：
文献类型：
--
作者：
Dishowitz, Michael I.;Terkhorn, Shawn P.;Hankenson, Kurt D.
先前的研究表明，Notch信号通过控制细胞增殖和分化来调节软骨内和膜内骨形成。Notch信号传导也被证明可以调节各种组织的愈合。本研究的目的是分别使用胫骨骨折和颅骨缺损损伤模型表征和比较软骨内和膜内骨愈合期间Notch信号通路的激活。双侧胫骨骨折还是双侧1.5？在小鼠中产生直径为1.5mm的颅骨缺损，并在骨折后0、5、10和20天收获组织。Notch信号传导组分的基因表达在胫骨骨折和颅骨缺损愈合期间均上调，在胫骨骨折愈合期间表达通常更高。愈合过程中最高表达的配体和受体Jag1和Notch2（特别是活化受体，称为NICD 2）在两种愈合模式中类似地定位于间充质细胞中，在软骨形成过程中表达减少，但在所有成熟阶段仍存在于成骨细胞中。结果表明，除了胚胎骨发育，Notch信号调节软骨内和膜内骨愈合。(C)2011年由Wiley Periodicals，Inc.出版的骨科研究学会。J Orthop Res 30：296303，2012
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. (C) 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:296303, 2012