Dexamethasone exposure accelerates endochondral ossification of chick embryos via angiogenesis

Xin Cheng, Yu Yan, Jian Long Chen, Zheng Lai Ma, Ren Hao Yang, Guang Wang, Manli Chuai, Kenneth Ka Ho Lee, Xuesong Yang (Lead / Corresponding author)

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9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)167-177
Number of pages11
JournalToxicological Sciences
Volume149
Issue number1
Early online date14 Oct 2015
DOIs
Publication statusPublished - 1 Jan 2016

Keywords

  • angiogenesis
  • chick embryos
  • Dexamethasone
  • mineralization
  • osteogenesis

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    Cheng, X., Yan, Y., Chen, J. L., Ma, Z. L., Yang, R. H., Wang, G., Chuai, M., Ka Ho Lee, K., & Yang, X. (2016). Dexamethasone exposure accelerates endochondral ossification of chick embryos via angiogenesis. Toxicological Sciences, 149(1), 167-177. https://doi.org/10.1093/toxsci/kfv227