Cheng Xin, Yan Yu, Chen Jian-long, Ma Zheng-lai, Yang Ren-hao, Wang Guang, Chuai Manli, Ka Ho Lee Kenneth, Yang Xuesong
*Department of Histology & Embryology, Joint Lab for Brain Function and Health, School of Medicine, Jinan University, Guangzhou 510632, China;
Division of Cell and Developmental Biology, University of Dundee, Dundee, DD1 5EH, UK;
Toxicol Sci. 2016 Jan;149(1):167-77. doi: 10.1093/toxsci/kfv227. Epub 2015 Oct 14.
Dexamethasone (Dex) is widely used to treat chronic inflammatory diseases in the clinic. Increasingly, there is more attention being paid to the side effect of Dex. In this study, we investigated the involvement and mechanism of Dex exposure in accelerating mineralization during long bone formation. We first determined that Dex exposure could accelerate long bone mineralization in vivo, but there was no apparent difference between control and Dex-treated in the phalanges model in vitro. Next, we established that Dex exposure promoted angiogenesis in the chick yolk sac membrane model. In addition, it increased human umbilical vein endothelial cell proliferation and migration in culture. We found that Dex could enhance angiogenesis when phalanges were cultured on chick chorioallantoic membrane and correspondingly increased the expression of angiogenesis-related genes in the phalanges. Furthermore, we also revealed that Dex exposure reduced the number of osteoblasts and simultaneously increased the number of osteocytes in ex vivo-cultured phalanges. Runx-2 and Col10α1 expressions were up-regulated by Dex exposure, indicating that Dex exposure accelerated the terminal differentiation of osteoblasts. Lastly, we demonstrated that MC3T3-E1 cells cultured in the presence of Dex accelerated their mineralization. In summary, we have shown that the ability of Dex to initiate angiogenesis is the mechanism that allows it to accelerate mineralization during long bone formation.
地塞米松（Dex）在临床上广泛用于治疗慢性炎症性疾病。越来越多的人开始关注Dex的副作用。在本研究中，我们调查了Dex暴露在长骨形成过程中加速矿化的参与情况及机制。我们首先确定，Dex暴露可在体内加速长骨矿化，但在体外指骨模型中，对照组和Dex处理组之间没有明显差异。接下来，我们证实Dex暴露在鸡胚卵黄囊膜模型中促进血管生成。此外，它还增加了培养的人脐静脉内皮细胞的增殖和迁移。我们发现，当指骨在鸡胚绒毛尿囊膜上培养时，Dex可增强血管生成，并相应增加指骨中血管生成相关基因的表达。此外，我们还发现，Dex暴露可减少体外培养指骨中成骨细胞的数量，同时增加骨细胞的数量。Dex暴露上调了Runx-2和Col10α1的表达，表明Dex暴露加速了成骨细胞的终末分化。最后，我们证明在Dex存在的情况下培养的MC3T3-E1细胞加速了它们的矿化。总之，我们已经表明，Dex启动血管生成的能力是其在长骨形成过程中加速矿化的机制。
