缺氧诱导因子-1α/-2α在膝骨关节炎的作用  

Role of hypoxiainducible factor-1α/-2αin knee osteoarthritis

作　　者：李培杰[1,2] 乔永杰 曾健康 周胜虎 LI Pei-jie;QIAO Yong-jie;ZENG Jian-kang;ZHOU Sheng-hu(The First Clinical Medical College,Gansu University of Traditional Chinese Medicine,Lanzhou,Gansu 730000,China;The 940^(th)Hospital,Joint Logistics Support Force of PLA,Lanzhou,Gansu 730000,China)

机构地区：[1]甘肃中医药大学第一临床医学院,甘肃兰州730000 [2]解放军联勤保障部队第九四〇医院关节外科,甘肃兰州730000

出　　处：《中国矫形外科杂志》2025年第6期511-516,共6页Orthopedic Journal of China

基　　金：甘肃省重点研发计划项目(编号:25YFFA064);甘肃省卫生健康行业科研项目(编号:GSWSKY2024-20);联勤保障部队第九四○医院高层次人才培养工程(编号:2024-G3-5);兰州市科技计划项目(编号:2023-2-11,2023-ZD-1707);甘肃中医药大学导师专项(编号:2023YXKY015)。

摘　　要：膝骨关节炎(knee osteoarthritis,KOA)是一种以关节软骨变性、破坏及骨质增生为特征的常见关节疾病。缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)和缺氧诱导因子-2α(hypoxia-inducible factor-2α,HIF-2α)是调节细胞对缺氧反应的核转录因子,对滑膜炎症、软骨变性以及骨质自噬等方面发挥着重要作用。HIF-1α主要维持软骨细胞的合成与分化,促进体内关节软骨自噬的平衡。HIF-2α则主要通过直接或间接调控各种分解代谢因子,导致关节软骨变性与降解。HIF-1α/-2α的表达除受氧感受器调节外,还受多条信号通路的调控,包括Wnt/β-catenin、NF-κB、AMPK/mTOR、PI3K/Akt、NLRP3、JAK2/STAT3等。本文综述了调控HIF-1α/-2α表达的信号通路,旨在为KOA的预防和治疗提供新的见解和思路。Knee osteoarthritis(KOA)is a common joint disease characterized by destruction of articular cartilage and osteophyte formation.Hypoxia-inducible factor-1α(HIF-1α)and hypoxia-inducible factor-2α(HIF-2α)are nuclear transcription factors that regulate the cellular response to hypoxia,and play important roles in synovial inflammation,cartilage degeneration,and bone autophagy.HIF-1αmainly maintains the synthesis and differentiation of chondrocytes and promotes the balance of articular cartilage autophagy in vivo,while HIF2αleads to the degeneration and degradation of articular cartilage mainly through the direct or indirect modulation of various catabolic factors.In addition to the regulation of the oxygen receptor,the expression of HIF-1α/-2αis regulated by several signaling pathways including Wnt/β-catenin,NF-κB,AMPK/mTOR,PI3K/Akt,NLRP3,JAK2/STAT3,and so on.This paper reviews the signaling pathways that regulate the expression of HIF-1α/-2α,aiming to provide new insights and ideas for the prevention and treatment of KOA.

关 键 词：膝骨关节炎 缺氧诱导因子-1Α 缺氧诱导因子-2Α 信号通路 

分 类 号：R684.3[医药卫生—骨科学]