Dimethyloxaloylglycine improves angiogenic activity of bone marrow stromal cells in the tissue-engineered bone

• Published in: International journal of biological sciences 2014-01, Vol.10 (7), p.746-756
• Main Authors: Ding, Hao, Chen, Song, Song, Wen-Qi, Gao, You-Shui, Guan, Jun-Jie, Wang, Yang, Sun, Yuan, Zhang, Chang-Qing
• Format: Article
• Language: English
• Subjects: Amino Acids, Dicarboxylic - pharmacology; Animals; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - physiology; Neovascularization, Physiologic - drug effects; Rats, Inbred F344; Research Paper; Skull - transplantation; Tissue Engineering - methods
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.8535

One of the big challenges in tissue engineering for treating large bone defects is to promote the angiogenesis of the tissue-engineered bone. Hypoxia inducible factor-1α (HIF-1α) plays an important role in angiogenesis-osteogenesis coupling during bone regeneration, and can activate a broad array of angiogenic factors. Dimethyloxaloylglycine (DMOG) can activate HIF-1α expression in cells at normal oxygen tension. In this study, we explored the effect of DMOG on the angiogenic activity of bone mesenchymal stem cells (BMSCs) in the tissue-engineered bone. The effect of different concentrations of DMOG on HIF-1a expression in BMSCs was detected with western blotting, and the mRNA expression and secretion of related angiogenic factors in DMOG-treated BMSCs were respectively analyzed using qRT-PCR and enzyme linked immunosorbent assay. The tissue-engineered bone constructed with β-tricalcium phosphate (β-TCP) and DMOG-treated BMSCs were implanted into the critical-sized calvarial defects to test the effectiveness of DMOG in improving the angiogenic activity of BMSCs in the tissue-engineered bone. The results showed DMOG significantly enhanced the mRNA expression and secretion of related angiogenic factors in BMSCs by activating the expression of HIF-1α. More newly formed blood vessels were observed in the group treated with β-TCP and DMOG-treated BMSCs than in other groups. And there were also more bone regeneration in the group treated with β-TCP and DMOG-treated BMSCs. Therefore, we believed DMOG could enhance the angiogenic activity of BMSCs by activating the expression of HIF-1α, thereby improve the angiogenesis of the tissue-engineered bone and its bone healing capacity.