缺氧信号在骨中的核心作用

缺氧信号在维持氧稳态和细胞生存中起着至关重要的作用。在胚胎发育时期处于快速增殖的细胞和肿瘤组织中快速生长的细胞中都能观察到缺氧现象的存在。为了应对缺氧胁迫，生物有机体形成了一系列的调节机制。在多种调节途径中，缺氧诱导因子HIF-1和HIF-2是最主要的能够应答细胞内氧气浓度的降低而对多种基因进行调控的转录因子，与生物体的生长发育及一些疾病的发病机理都存在着密切关系。最近的研究发现在骨骼发育，骨骼的形成和再生，以及关节的形成和动态平衡的调节中HIF-1和HIF-2的具有重要作用。此外，HIF-1和HIF-2的过度表达在临床上与骨肉瘤和骨关节炎明显相关。总之，这些发现预示着缺氧的信号在骨骼的生物学及其疾病中起到中心调节的作用。

A Central Role for Hypoxic Signaling in Bone

Hypoxic signaling plays an important role in maintaining oxygen homeostasis and cell survival. In the embryonic development period, hypoxia phenomena can be observed in rapidly proliferated cells and tumor tissue. In order to deal with hypoxia stress, organisms formed a series of regulatory mechanism. In a variety of regulatory paths, hypoxia-inducible factors （HIF）, HIF-1 and HIF-2, are the most dominant ones which can regulate multiple genes through responsing to reduction of oxygen concentration in cells and there are close relations among HIF, growth development of the organism and pathogenesis of some disease. Recent studies have identified an important role for HIF-1 and HIF-2 in the regulation of skeletal development, bone formation and regeneration, as well as joint formation and homeostasis. In addition, over expression of HIF-1 and HIF-2 is clinically associated with osteosarcoma and osteoarthritis. In short, these findings implicate hypoxic signaling as a central regulator of bone biology and disease.