HIF-1α在骨血管及骨代谢方面与骨质疏松症相关性研究进展

Research progress of the correlation between HIF-1αin bone vascular and bone metabolism and osteoporosis

骨质疏松症(osteoporosis,OP)是一种骨退行性慢性代谢性疾病,以骨量减少、骨组织微观结构退化,易骨折和骨的力学性能下降为特征。骨血管的生成、骨代谢中骨生成和骨吸收的平衡以及骨髓间充质干细胞的增殖、迁移和向成骨分化作用对于骨质疏松的发生发展及防治至关重要,氧是骨细胞生长、发育及功能代谢的重要条件,骨微环境处于天然的低氧状态下,其中维持骨稳态的成骨细胞和破骨细胞均属于氧感应细胞,缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)是具有转录活性的核蛋白,其活性亚基HIF-1α是细胞感知和适应氧调节机制的核心调控因子,在细胞氧调控中发挥着不可替代的作用,HIF-1α对骨血管生成以及骨代谢作用的研究为骨质疏松症的防治提供了更多可能。研究证明HIF-1α可通过多种信号通路、蛋白、miRNA等调节骨血管生成、成骨细胞和破骨细胞生成分化,调控骨髓间充质干细胞的增殖、迁移以及向成骨分化作用,HIF-1α可能成为防治骨质疏松症极具潜力的新靶点。本文旨在综述HIF-1α在骨血管生成及骨代谢方面对骨质疏松症发生发展的影响及防治作用。

Osteoporosis(OP)is a chronic metabolic disease of bone degeneration,which is characterized by reduction of bone mass,degeneration of microstructure of bone tissue,easy fracture and decline of mechanical properties of bone.The formation of bone vessels,the balance of bone formation and bone resorption in bone metabolism,and the proliferation,migration,and osteogenic differentiation of bone marrow mesenchymal stem cells are very important for the occurrence,development,prevention,and treatment of osteoporosis.Oxygen is an important condition for the growth,development,and functional metabolism of osteocytes.The bone microenvironment is in a state of natural hypoxia,in which osteoblasts and osteoclasts that maintain bone homeostasis belong to oxygen-sensitive cells.Hypoxia inducible factor-1(HIF-1)is a nuclear protein with transcriptional activity,and its active subunit HIF-1αis the core regulator of cellular perception and adaptive oxygen regulation,which plays an irreplaceable role in cellular oxygen regulation.The study of HIF-1αon bone angiogenesis and bone metabolism provides more possibilities for the prevention and treatment of osteoporosis.Studies have shown that HIF-1αcan regulate bone angiogenesis,osteoblast and osteoclast differentiation through a variety of signal pathways,protein and miRNA,and regulate the proliferation,migration,and osteogenic differentiation of bone marrow mesenchymal stem cells.HIF-1αmay be a potential new target for the prevention and treatment of osteoporosis.The purpose of this article is to review the effect of HIF-1αon the occurrence and development of osteoporosis and its preventive and therapeutic effect on bone angiogenesis and bone metabolism.