Chinese Journal of Tissue Engineering Research ›› 2023, Vol. 27 ›› Issue (24): 3865-3870.doi: 10.12307/2023.699

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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   

  1. 1Binzhou Medical College, Binzhou 256603, Shandong Province, China; 2Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou 256603, Shandong Province, China
  • Received:2022-09-17 Accepted:2022-10-29 Online:2023-08-28 Published:2023-01-18
  • Contact: Fu Honghai, Master, Attending physician, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou 256603, Shandong Province, China Zuo Jinhua, MD, Chief physician, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou 256603, Shandong Province, China
  • About author:Tang Juan, Master candidate, Binzhou Medical College, Binzhou 256603, Shandong Province, China
  • Supported by:
    Natural Science Foundation of Shandong Province, No. ZR2018PH023 (to FHH); Xu Rongxiang Regenerative Medicine Project of Binzhou Medical College, No. BY2020XRX011 (to FHH)

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

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