缺氧诱导因子-1α/-2α在膝骨关节炎的作用△

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

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。

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

Abstract:

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-1α mainly maintains the synthesis and differentiation of chondrocytes and promotes the balance of articular cartilage autophagy in vivo, while HIF2α leads 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/-2α is 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.

Key words:knee osteoarthritis; hypoxia-inducible factor-1α; hypoxia-inducible factor-2α; signaling pathway