低氧条件下HIF-1α对骨生理中成骨和破骨的影响  

Effects of HIF-1αon osteogenesis and osteoblastogenesis in bone physiology under hypoxic conditions

作　　者：范智博 魏绵兴 李胜鸿(综述) 徐晓梅(审校) FAN Zhibo;WEI Mianxing;LI Shenghong;XU Xiaomei(Department of Orthodontics,The Affiliated Stomatological Hospital,Southwest Medical University,Luzhou 646000,China;Depart-ment of Cleft Lip and Palate Surgery,West China Hospital of Stomatology Sichuan University,Chengdu 610041,China)

机构地区：[1]西南医科大学附属口腔医院正畸科,泸州646000 [2]四川大学华西口腔医院唇腭裂外科,成都610041

出　　处：《西南医科大学学报》2024年第1期80-86,共7页Journal of Southwest Medical University

基　　金：四川省科技厅科技计划联合创新专项项目(2022YFS0634-B3);四川省医学会项目(S23016)。

摘　　要：骨的吸收、生成及稳态的维持是建立在成骨和破骨事件基础上的,上述这些过程是由多种因子共同参与调控。其中缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)作为低氧的标志物,已被证实参与了多种成骨及破骨过程。各种体内外低氧模型也提供了HIF-1α直接或间接调控成骨及破骨过程的相关证据,但其对成骨及破骨的影响及机制并未得到系统性总结。所以本文对HIF-1α参与成骨、破骨的调控机制及其所涉及的相关临床事件进行了综述。总的来说,低氧条件下HIF-1α主要是通过与成骨及破骨相关基因的缺氧反应元件(hy-poxia response element,HRE)结合从而直接参与成骨及破骨过程。除此之外,HIF-1α还可以通过增强糖酵解从而维持成骨及破骨能量的需求,但与此同时酸化的环境会进一步刺激破骨的产生。通过文献回顾,我们发现低氧条件下HIF-1α调控的成骨及破骨两种不同事件可能与低氧的持续时间和浓度有着密切联系,而不同氧条件下所导致的糖酵解的酸化程度可能是决定HIF-1α介导成骨和破骨走向的关键因素。低氧持续时间作为“低氧剂量”的一个组成部分对骨生理反应有着重要影响,同时其激发的HIF亚型转化这一现象对骨生理的影响也至关重要。据此本文通过对低氧下HIF-1α在成骨破骨进程的调控作用进行综述,以期为低氧下骨生理调控的相关机制提供一定的理论参考。Bone resorption,formation and homeostasis maintenance are based on osteogenic and osteoclastic phenomenon,which include the regulation of a variety of factors.HIF-1α,as a marker of hypoxia,has been confirmed participating in a variety of process related to osteogenesis and osteoclast.And various vivo and in vitro hypoxia models have further revealed that HIF-1αcan regulate bone physiology.These studies provide direct or indirect evidence that HIF-1αregulates osteogenic and osteoclastic events,but the ef-fects of HIF-1αon osteogenesis and osteoclasty have not been systematically summarized.This review summarized the mechanism of regulation of HIF-1αon osteogenesis and osteoclasty and its participation in relevant clinical events.HIF-1αdirectly participates in os-teogenesis and osteoclasty mainly through combing with the hypoxia response element(HRE)of osteogenesis related gene and osteoclast related gene under hypoxia.In addition,HIF-1αcan also achieve the energy demand of osteogenic and osteoclastic events by enhancing glycolysis.But at the same time,the acidified environment will further stimulate the actvition of osteoclasts.Through the above review,we found that the two different events of osteogenesis and osteoclast regulated by HIF-1αmay be closely related to the duration and con-centration of hypoxia,and the acidification degree of glycolysis under different oxygen conditions,mediated by HIF-1α,may be the key factors that determine the trend of osteogenesis and osteoclast.We believe that hypoxia duration,as a part of"hypoxia dose",should have an important impact on bone physiology,which needs more attention in future research.At the same time,in the state of continuous hypoxia,the transformation of HIF subtypes is also worthy of more in-depth study on the impact of bone physiology.Therefore,this ar-ticle focuses on the effect of HIF-1αon osteogenesis and osteoclasis process under hypoxia,and provide a theoretical basis for the regu-lation mechanisms of bone physiological changes under hypoxia.

关 键 词：低氧 缺氧诱导因子-1Α 成骨 破骨 

分 类 号：R336[医药卫生—人体生理学]