HIF-1α increases the osteogenic capacity of ADSCs by coupling angiogenesis and osteogenesis via the HIF-1α/VEGF/AKT/mTOR signaling pathway

Journal of Nanobiotechnology

Research

Zijun Chen¹  Xutao Chen¹  Guanhua Zhang¹  Yingliang Song¹  Xiangdong Liu¹  Jian Zheng¹  Yuxi Wang¹  Yiqing Wang²  Shuang Song³  Qin Zhou³ 

[1] Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University, 710032, Xi’an, China;Department of Prosthodontics, Peking University School and Hospital of Stomatology, 100081, Beijing, China;Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, 710004, Xi’an, China;

关键词: Hypoxia-inducible factor 1α;    Adipose-derived stem cells;    Osteointegration;    Osteogenic differentiation;    Stem cell transplantation;    HIF-1α/VEGF/AKT/mTOR signaling pathway;    Titanium implant;   

DOI  :  10.1186/s12951-023-02020-z

 received in 2023-04-20, accepted in 2023-07-23,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundStabilization and increased activity of hypoxia-inducible factor 1-α (HIF-1α) can directly increase cancellous bone formation and play an essential role in bone modeling and remodeling. However, whether an increased HIF-1α expression in adipose-derived stem cells (ADSCs) increases osteogenic capacity and promotes bone regeneration is not known.ResultsIn this study, ADSCs transfected with small interfering RNA and HIF-1α overexpression plasmid were established to investigate the proliferation, migration, adhesion, and osteogenic capacity of ADSCs and the angiogenic ability of human umbilical vein endothelial cells (HUVECs). Overexpression of HIF-1α could promote the biological functions of ADSCs, and the angiogenic ability of HUVECs. Western blotting showed that the protein levels of osteogenesis-related factors were increased when HIF-1α was overexpressed. Furthermore, the influence of upregulation of HIF-1α in ADSC sheets on osseointegration was evaluated using a Sprague–Dawley (SD) rats implant model, in which the bone mass and osteoid mineralization speed were evaluated by radiological and histological analysis. The overexpression of HIF-1α in ADSCs enhanced bone remodeling and osseointegration around titanium implants. However, transfecting the small interfering RNA (siRNA) of HIF-1α in ADSCs attenuated their osteogenic and angiogenic capacity. Finally, it was confirmed in vitro that HIF-1α promotes osteogenic differentiation and the biological functions in ADSCs via the VEGF/AKT/mTOR pathway.ConclusionsThis study demonstrates that HIF-1α has a critical ability to promote osteogenic differentiation in ADSCs by coupling osteogenesis and angiogenesis via the VEGF/AKT/mTOR signaling pathway, which in turn increases osteointegration and bone formation around titanium implants.Graphical Abstract

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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