2023, Vol. 27 ›› Issue (24): 3865-3870

Osteogenic and angiogenic differentiation of dental pulp stem cells modified by hypoxia-inducible factor-1 alpha gene in vitro

Tang Juan1, Yu Donglin1, Liu Guoqi1, Song Jiaojiao1, Zuo Jinhua2, Fu Honghai2   

Abstract: BACKGROUND: How to effectively repair and reconstruct critical bone defects has become a difficult problem in clinical medicine. Dental pulp stem cells have certain advantages as transgenic target cells to repair damaged tissues or organs.
OBJECTIVE: To investigate the effect of hypoxia-inducible factor-1α on osteogenesis and angiogenesis of dental pulp stem cells in vitro.
METHODS: The pulp tissues of healthy and intact bicuspid teeth extracted by orthodontic treatment in patients aged 12 to 18 years were isolated to culture dental pulp stem cells. The hypoxia-inducible factor-1α gene was transfected into dental pulp stem cells in the experimental group. The control group did not do any treatment. The expression of the hypoxia-inducible factor 1α gene was detected by qPCR and the expression of osteogenic and angiogenic factors was detected by western blot assay.
RESULTS AND CONCLUSION: (1) Dental pulp stem cells were short spindle-shaped fibroblast-like cells, and the cells grew in colonies. (2) Hypoxia-inducible factor-1α gene was stably transfected into dental pulp stem cells. The expression of the hypoxia-inducible factor-1α gene increased gradually with the extension of time, reached a peak at 14 days, and significantly decreased at 21 days. (3) Compared with the control group, the expression level of angiogenesis-related factors in the experimental group was higher. The protein expression levels of vascular endothelial growth factor, stromal cell-derived factor 1, angiopoietin 2, and placental growth factor were significantly increased at 1 day after gene transfection and reached a peak at 4 days. After that, the expression of angiogenesis-associated protein in the experimental group decreased slightly, but was significantly higher than that in the control group. (4) Compared with the control group, the expression level of osteogenic-related factors in the experimental group was higher. The protein expression levels of human bone morphogenetic protein 2, osteocalcin, and Runt-related transcription factor 2 were significantly increased at 1 day after gene transfection, with the highest protein expression at 4 days. (5) It is concluded that hypoxia-inducible factor-1α can promote the osteogenesis and the expression of angiogenic factors in dental pulp stem cells.  

Key words: dental pulp stem cell, hypoxia-inducible factor-1α, vascular endothelial growth factor, bone morphogenetic protein 2, growth factor, stromal cell-derived factor 1, angiopoietin 2