Objective to review the development and applications and intervention factors of hypoxia-inducible factor 1α (HIF-1α) in the strategy of tissue engineered angiogenesis and osteogenesis. Methods the literature about HIF-1α in tissue engineering technology was reviewed, analyzed, and summarized. Results HIF-1α and its intervention factors plays a key role in angiogenicosteogenic coupling, and as an upstream regulator.

Yinxuan Pu, Hao Sun, Quan Yang, Yu Su, Shangyi Lv, Bangxiu Zheng, Xiangzhen Han, Huiyu He. Research Progress of HIF- 1α and its Intervention Factors in Osteogenic Synthesis of Blood Vessels in Bone Marrow Mesenchymal Stem Cells. Frontiers in Medical Science Research (2021) Vol. 3 Issue 2: 24-28. https://doi.org/10.25236/FMSR.2021.030207.

[1] Li H, Zhao B, Liu Y, et al. Angiogenesis in residual cancer and roles of HIF-1alpha, VEGF, and MMP-9 in the development of residual cancer after radiofrequency ablation and surgical resection in rabbits with liver cancer[ J]. Folia Morphol (Warsz), 2020, 79(1):71-78.

[2] Liu Y, Tang J, Hu Q, et al. A preliminary study on the expression and clinical value of platelet-derived growth factor BB, hypoxia inducible factor-1 alpha and CC motif chemokine receptor-2 in peripheral blood during the pathogenesis of Graves' disease [J]. ENDOKRYNOLOGIA POLSKA, 2018, 69(1):9-15.

[3] Xie YB, Li JP, Shen K, et al. [Effect of HIF-1alpha on Angiogenesis-Related Factors in K562 Cells [J]. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2019, 27(5): 1476 -1481.

[4] Hamushan M, Cai W, Zhang Y, et al. High-purity magnesium pin enhances bone consolidation in distraction osteogenesis model through activation of the VHL/HIF-1alpha/VEGF signaling[J]. J Biomater Appl, 2020, 35 (2):224-236.

[5] Cimmino F, Avitabile M, Lasorsa V A, et al. HIF-1 transcription activity: HIF1A driven response in normoxia and in hypoxia [J]. BMC Med Genet, 2019, 20 (1): 37.

[6] Khuu M A. Lessons from neuronal HIF1a: Understanding its role in ventilatory acclimatization to hypoxia [J]. J Physiol, 2020.

[7] Hu CJ, Wang LY, Chodosh LA, et al. Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation [J]. Mol Cell Biol, 2003, 23(24): 9361-9374.

[8] Ivan M1, Kondo K, Yang H, et al.HIFalpha targeted for VHL-mediated destruction by proline hydroxylation;implications for O2 sensing[J].Science.2001, 292:464-8.

[9] Martinez VG, Ontoria-Oviedo I, Ricardo CP, et al. Overexpression of hypoxia-inducible factor 1 alpha improves immunomodulation by dental mesenchymal stem cells [J]. Stem Cell Res Ther, 2017, 8(1): 208.

[10] Taheem D K, Jell G, Gentleman E. Hypoxia Inducible Factor-1alpha in Osteochondral Tissue Engineering [J]. Tissue Eng Part B Rev, 2020, 26 (2): 105-115.

[11] Niyaz M, Gurpinar O A, Oktar G L, et al. Effects of VEGF and MSCs on vascular regeneration in a trauma model in rats [J]. Wound Repair Regen, 2015, 23 (2): 262-267.

[12] Tian X, Zhou N, Yuan J, et al. Heat shock transcription factor 1 regulates exercise-induced myocardial angiogenesis after pressure overload via HIF-1alpha/VEGF pathway [J]. J Cell Mol Med, 2020, 24(3): 2178-2188.

[13] Zelzer E, Olsen B R. Multiple roles of vascular endothelial growth factor (VEGF) in skeletal development, growth, and repair [J]. Curr Top Dev Biol, 2005, 65: 169-187.

[14] Sun J, Shen H, Shao L, Teng X, Chen Y, Liu X, Yang Z, Shen Z. HIF-1α overexpression in mesenchymal stem cell-derived exosomes mediates cardioprotection in myocardial infarction by enhanced angiogenesis. Stem Cell Res Ther. 2020 Aug 28; 11(1): 373.

[15] Gonzalez-King H, Garcia NA, Ontoria-Oviedo I, et al. Hypoxia Inducible Factor-1alpha Potentiates Jagged 1-Mediated Angiogenesis by Mesenchymal Stem Cell-Derived Exosomes [J]. Stem Cells, 2017, 35(7): 1747-1759.

[16] Wang X, Shen K, Wang J, et al. Hypoxic preconditioning combined with curcumin promotes cell survival and mitochondrial quality of bone marrow mesenchymal stem cells, and accelerates cutaneous wound healing via PGC-1 alpha/SIRT3/HIF-1 alpha signaling[J]. FREE RADICAL BIOLOGY AND MEDICINE, 2020, 159:164-176.

[17] Yu H, Yu W, Liu Y, et al. Expression of HIF1alpha in cycling stretchinduced osteogenic differentiation of bone mesenchymal stem cells [J]. Mol Med Rep, 2019, 20 (5): 4489-4498.

[18] Zhang Y, Hao Z, Wang P, et al. Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF-1alpha-mediated promotion of angiogenesis in a rat model of stabilized fracture[J]. Cell Prolif, 2019, 52(2): e12570.

[19] Tian Dachuan, Li Haile, Xiao Dawei, Zhou Shanjian, Su Yongwei, Liu Danping, Qi Hui. Combined application of cartilage regeneration scaffold and mutant HIF-1α modified exosomes secreted by BMSCs can promote the repair of advanced cartilage defects [J]. Journal of Jilin University (Medical Edition), 2018, 44(02):216-222+461.

[20] Zhu Yanqiu. Experimental study of HIF-1α-mediated BMSCs combined with PLGA in repairing rat skull standard bone defects [D]. Anhui Medical University, 2017.

[21] Van de Walle A, Faissal W, Wilhelm C, et al. Role of growth factors and oxygen to limit hypertrophy and impact of high magnetic nanoparticles dose during stem cell chondrogenesis[J]. Comput Struct Biotechnol J, 2018, 16: 532-542.

[22] Huang Y, Wang X, Lin H. The hypoxic microenvironment: a driving force for heterotopic ossification progression [J]. Cell Commun Signal, 2020, 18(1):20.

[23] Huang Jiao. The effect of hypoxic microenvironment on the osteogenic differentiation of bone marrow mesenchymal stem cells [D]. Chongqing Medical University, 2012.

[24] Zhuo Yi. Research on the promotion of OM-MSCs proliferation and differentiation into dopaminergic neurons in hypoxic microenvironment [D]. Hunan Normal University, 2016.

[25] Wang Jun, Han Lichun, Sun Xude, Li Zhengmin, Zhang Zhen, Zhang Ru, Zhang Yuming. Effects of chemical hypoxia induced by cobalt chloride on the biological characteristics of rat bone marrow mesenchymal stem cells transfected with HIF-1α gene [J]. Modern Oncology Medicine, 2018, 26(15): 2320-2325.

[26] Sen T, Sen N. Treatment with an activator of hypoxia-inducible factor 1, DMOG provides neuroprotection after traumatic brain injury [J]. Neuropharmacology, 2016, 107:79-88.

[27] Jing X, Du T, Yang X, et al. Desferoxamine protects against glucocorticoid-induced osteonecrosis of the femoral head via activating HIF-1alpha expression [J]. J Cell Physiol, 2020, 235(12):9864-9875.

[28] Wang K, Jing Y, Xu C, et al. HIF-1alpha and VEGF Are Involved in Deferoxamine-Ameliorated Traumatic Brain Injury [J]. J Surg Res, 2020, 246: 419-426.

[29] Choi C W, Lee J, Lee H J, et al. Deferoxamine Improves Alveolar and Pulmonary Vascular Development by Upregulating Hypoxia-inducible Factor-1 alpha in a Rat Model of Bronchopulmonary Dysplasia[J]. JOURNAL OF KOREAN MEDICAL SCIENCE, 2015, 30 (9): 1295-1301. 

[30] Taheem D K, Foyt D A, Loaiza S, et al. Differential Regulation of Human Bone Marrow Mesenchymal Stromal Cell Chondrogenesis by Hypoxia Inducible Factor-1alpha Hydroxylase Inhibitors [J]. Stem Cells, 2018, 36(9): 1380-1392. 

[31] Zhou B, Ge T, Zhou L, et al. Dimethyloxalyl Glycine Regulates the HIF-1 Signaling Pathway in Mesenchymal Stem Cells [J]. Stem Cell Rev Rep, 2020; 16(4): 702-10.

[32] Basavaraju A M, Shivanna N, Yadavalli C, et al. Ameliorative Effect of Ananas comosus on Cobalt Chloride-Induced Hypoxia in Caco2 cells via HIF-1alpha, GLUT 1, VEGF, ANG and FGF[J]. Biol Trace Elem Res, 2020. 

[33] Tripathi V K, Subramaniyan S A, Hwang I. Molecular and Cellular Response of Co-cultured Cells toward Cobalt Chloride (CoCl2)-Induced Hypoxia [J]. ACS Omega, 2019, 4 (25): 20882-20893. 

[34] Dai Y, Li W, Zhong M, et al. The paracrine effect of cobalt chloride on BMSCs during cognitive function rescue in the HIBD rat [J]. Behav Brain Res, 2017, 332: 99-109.