AMPK在组织工程骨促骨再生研究中的应用及进展

Application and progress of AMPK in the study of promoting bone regeneration by tissue engineered bone

组织工程骨(tissue engineered bone,TEB)由于其材料范围广泛,骨传导性及骨诱导能力极佳,在大段骨缺损的治疗及骨再生领域显示出广阔的前景。TEB与骨缺损处的血管再生过程极其复杂,需要种子细胞及细胞产生的各种生长因子的参与,而间充质干细胞(mesenchymal stem cells,MSCs)取材方便,伦理争议及免疫原性低,且具有成骨及成血管分化等能力,已作为骨缺损修复治疗中的新方式,可改善目前现有治疗方法的缺点及提高临床治疗效果。AMP活化蛋白激酶(AMP-activated protein kinase,AMPK)是真核生物中调节细胞能量稳态及多种代谢相关激素的重要分子,可被多种途径激活而发挥生理调控作用。近年来,研究发现它与骨再生及骨微环境形成等生理过程密切相关,通过作用于MSCs、成骨细胞、破骨细胞及血管再生等发挥促成骨效应,也有不少研究者利用AMPK与MSCs联合治疗骨损伤的再生修复,在TEB促骨再生中产生积极影响。另外,该文也总结出AMPK参与骨再生作用机制可能与活性氧、细胞自噬及沉默信息调节因子1等信号通路有关。笔者就AMPK在TEB促骨再生中的研究及机制作一综述,旨在为骨缺损修复、骨再生靶向治疗及相关分子机制研究提供理论依据和新的思路。

Tissue engineered bone(TEB),due to its wide range of materials,excellent osteoconductivity,and osteoinductive capacity,has shown broad prospects in the treatment of large-scale bone defects and bone regeneration.The angiogenesis process of TEB and bone defect are extremely complex,requiring the participation of seed cells and various growth factors produced by cells.Mesenchymal stem cells(MSCs)are readily available,have less ethical controversy and low immunogenicity,and have the ability of osteogenic and angiogenic differentiation.It has been used as a new method to repair bone defects,which can overcome the shortcomings of the existing treatment method and improve the clinical treatment effect.AMP-activated protein kinase(AMPK)is an important molecule that regulates cell energy homeostasis and a variety of metabolism-related hormones in eukaryotes.It can be activated by many pathways to play a physiological regulatory role.In recent years,studies have found that it is related to physiological processes of bone regeneration and bone microenvironment formation.It exerts an osteogenic effect by acting on MSCs,osteoblasts,osteoclasts,and angiogenesis.Many researchers have used AMPK and MSCs in combination to treat regeneration and repair of bone injury,which has a positive effect on TEB in promoting bone regeneration.In addition,this article also concludes that AMPK is involved in bone regeneration,which may be related to signal pathways such as reactive oxygen species,autophagy,and silent information regulator 1.This paper reviews the research and mechanism of AMPK in TEB promoting bone regeneration,aiming to provide theoretical basis and new ideas for bone defect repair,targeted therapy of bone regeneration and related molecular mechanisms.