ETV2 regulating PHD2-HIF-1αaxis controls metabolism reprogramming promotes vascularized bone regeneration
作者机构：College&Hospital of StomatologyAnhui Medical UniversityKey Lab.of Oral Diseases Research of Anhui ProvinceHefei230032China Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function ReconstructionBeijing Laboratory of Oral Health and Beijing Stomatological HospitalCapital Medical UniversityBeijing100050China Department of VIP Dental ServiceSchool of StomatologyCapital Medical UniversityBeijing100050China Laboratory for Oral and General Health Integration and TranslationBeijing Tiantan HospitalCapital Medical UniversityBeijingChina
出 版 物：《Bioactive Materials》 (生物活性材料（英文）)
年 卷 期：2024年第37卷第7期
页 面：222-238页
核心收录：
基 金：supported by the National Natural Science Foundation of China (grants 82301039) the Natural Science Foundation of the Anhui Higher Education Institutions of China (grant 2022AH050758) Anhui Institute of Translational Medicine,Natural Sciences (grant 2022zhyx-C87) National Natural Science Foundation of China (82170951) Beijing Municipal Natural Science Foundation (7222079)
主 题：Vascularized bone regeneration ETV2 Hypoxia-inducible factor-1α Metabolism reprogramming Microsphere
摘 要：The synchronized development of mineralized bone and blood vessels is a fundamental requirement for successful bone tissue *** energy production forms the cornerstone supporting new bone *** variant 2(ETV2)has been identified as a transcription factor that promotes energy metabolism reprogramming and facilitates the coordination between osteogenesis and *** vitro molecular experiments have demonstrated that ETV2 enhances osteogenic differentiation of dental pulp stem cells(DPSCs)by regulating the ETV2-prolyl hydroxylase 2(PHD2)-hypoxia-inducible factor-1α(HIF-1α)-vascular endothelial growth factor A(VEGFA)***,ETV2 achieves the rapid reprogramming of energy metabolism by simultaneously accelerating mitochondrial aerobic respiration and glycolysis,thus fulfilling the energy requirements essential to expedite osteogenic ***,decreasedα-ketoglutarate release from ETV2-modified DPSCs contributes to microcirculation ***,we engineered hydroxyapatite/chitosan microspheres(HA/CS MS)with biomimetic nanostructures to facilitate multiple ETV2-DPSC functions and further enhanced the osteogenic *** experiments have validated the synergistic effect of ETV2-modified DPSCs and HA/CS MS in promoting the critical-size bone defect *** summary,this study offers a novel treatment approach for vascularized bone tissue regeneration that relies on energy metabolism activation and the maintenance of a stable local hypoxia signaling state.
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