Dexamethasone Exposure Accelerates Endochondral Ossification of Chick Embryos Via Angiogenesis

• Published in: Toxicological sciences Vol. 149; no. 1; pp. 167 - 177
• Main Authors: Cheng, Xin, Yan, Yu, Chen, Jian-long, Ma, Zheng-lai, Yang, Ren-hao, Wang, Guang, Chuai, Manli, Ka Ho Lee, Kenneth, Yang, Xuesong
• Format: Journal Article
• Language: English
• Published: United States 01.01.2016
• Subjects: Animals; Calcification, Physiologic - drug effects; Calcification, Physiologic - physiology; Cell Proliferation - drug effects; Cells, Cultured; Chick Embryo; Dexamethasone - pharmacology; Human Umbilical Vein Endothelial Cells - drug effects; Humans; Mice; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Osteoblasts - drug effects; dexamethasone; mineralization; chick embryos; osteogenesis; angiogenesis
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/kfv227

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.