HIF-1α Regulates Bone Homeostasis and Angiogenesis, Participating in the Occurrence of Bone Metabolic Diseases

In the physiological condition, the skeletal system's bone resorption and formation are in dynamic balance, called bone homeostasis. However, bone homeostasis is destroyed under pathological conditions, leading to the occurrence of bone metabolism diseases. The expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) is regulated by oxygen concentration. It affects energy metabolism, which plays a vital role in preventing bone metabolic diseases. This review focuses on the HIF-1 alpha pathway and describes in detail the possible mechanism of its involvement in the regulation of bone homeostasis and angiogenesis, as well as the current experimental studies on the use of HIF-1 alpha in the prevention of bone metabolic diseases. HIF-1 alpha/RANKL/Notch1 pathway bidirectionally regulates the differentiation of macrophages into osteoclasts under different conditions. In addition, HIF-1 alpha is also regulated by many factors, including hypoxia, cofactor activity, non-coding RNA, trace elements, etc. As a pivotal pathway for coupling angiogenesis and osteogenesis, HIF-1 alpha has been widely studied in bone metabolic diseases such as bone defect, osteoporosis, osteonecrosis of the femoral head, fracture, and nonunion. The wide application of biomaterials in bone metabolism also provides a reasonable basis for the experimental study of HIF-1 alpha in preventing bone metabolic diseases.

Automated summary

In physiological conditions, the bone resorption and formation in the skeletal system are balanced, maintaining bone homeostasis. However, under pathological conditions, bone homeostasis is disrupted, leading to bone metabolic diseases. The hypoxia-inducible factor-1 alpha (HIF-1 alpha) pathway, which is regulated by oxygen concentration, plays a crucial role in preventing bone metabolic diseases by influencing energy metabolism. This review focuses on the involvement of HIF-1 alpha in regulating bone homeostasis and angiogenesis, as well as its potential use in preventing bone metabolic diseases through current experimental studies. The HIF-1 alpha/RANKL/Notch1 pathway bidirectionally regulates macrophage differentiation into osteoclasts under different conditions. Moreover, HIF-1 alpha is regulated by various factors, including hypoxia, cofactor activity, non-coding RNA, and trace elements. As a key pathway linking angiogenesis and osteogenesis, HIF-1 alpha has been extensively studied in bone metabolic diseases such as bone defects, osteoporosis, osteonecrosis of the femoral head, fractures, and nonunion. The wide application of biomaterials in bone metabolism also provides a solid foundation for experimental studies on the role of HIF-1 alpha in preventing bone metabolic diseases.