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Biomed Pharmacother. 2018 Sep;105:932-939. doi: 10.1016/j.biopha.2018.06.078. Epub 2018 Jun 19.

Angiopoietin 2 promotes angiogenesis in tissue-engineered bone and improves repair of bone defects by inducing autophagy.

Author information

1
Department of Orthopedics, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, 211100, China.
2
Department of Geriatrics, Jinling Hospital, Medical School of Nanjing University, Nanjing, 211002, China.
3
Department of Orthopedics, Lianyungang First People's Hospital, 222000, Lianyungang, China.
4
Department of Orthopedics, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, 211100, China. Electronic address: liuxinhuijnyy@163.com.

Abstract

Angiogenesis plays a key role in the repair of large segmental bone defects with tissue-engineered bones. However, there is no effective method of promoting angiogenesis in tissue-engineered bone. Both angiopoietin 2 (Ang2) and autophagy have been shown to be involved in angiogenesis, but their roles in angiogenesis of tissue-engineered bone remains unknown. In this in vivo study, a radius bone defect was created in New Zealand white rabbits, which were then treated by implantation of a hydroxyapatite/collagen scaffold followed by injection of different concentrations of Ang2. Expression of the autophagic modulators microtubule-associated protein 1 light chain 3 (LC3), Beclin-1, and SQSTM1/P62 were measured via western blotting, while the angiogenic modulators VEGF and CD31 were detected by western blotting and immunohistochemistry, respectively. X-ray imaging combined with general observation was used to evaluate bone defect healing. Expression of LC3 -I/LC3-II, Beclin-1, VEGF, and CD31 in the callus area increased and SQSTM1/p62 decreased in a dose-dependent manner with increasing Ang2 concentration. In the group treated with a high concentration of Ang2, the new callus grew well, accompanied by remarkable angiogenesis, leading to good repair of the bone defects. However, in the low concentration of Ang2 group, in spite of the existence of angiogenesis and new bone formation, the bone defects were not repaired. Furthermore, angiogenesis and osteogenesis were both obstructed in the control group. In conclusion, our study demonstrated that a high concentration of Ang2 promoted angiogenesis in tissue-engineered bone and improved repair of bone defects by inducing autophagy.

KEYWORDS:

Angiogenesis; Angiopoietin 2; Autophagy; Bone defect; Tissue-engineered bone

PMID:
30021387
DOI:
10.1016/j.biopha.2018.06.078
[Indexed for MEDLINE]

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