2022, Vol. 26 ›› Issue (33): 5393-5399

Relationship between hypoxia-inducible factors and bone homeostasis disorders

Li Hongyuan1, Yang Liu2, Jin Xianhui1   

Abstract: BACKGROUND: Hypoxia-inducible factor is a key gene expression regulator in the bone hypoxia microenvironment. It is of great significance to understand the mechanism of hypoxia-inducible factors in bone formation and remodeling, and to analyze its effect on bone homeostasis imbalance diseases for exploring new ways to prevent and treat bone homeostasis imbalance diseases.
OBJECTIVE: To consult relevant medical articles at home and abroad to review and analyze the mechanism of hypoxia-inducible factors in the process of bone formation and bone remodeling, as well as the research progress of the relationship between hypoxia-inducible factors and bone homeostasis disorders.
METHODS: In April 2021, we searched CNKI, Wanfang, VIP, NCBI, and PubMed for articles published from 2000 to 2021, with the Chinese and English key words of “hypoxia inducible factor, bone formation, bone remodeling, bone homeostasis disorders, regulatory mechanism”. Through the sorting and analysis of relevant data, the mechanisms of hypoxia-inducible factors on bone formation and bone remodeling were reviewed and the effect of hypoxia-inducible factors on bone homeostasis disorders was analyzed.
RESULTS AND CONCLUSION: (1) Hypoxia-inducible factor-1α overexpression in osteoblasts under the hypoxic stress promotes bone formation and increases long bone volume, while the significant upregulation of hypoxia-inducible factor-2α expression in osteoblasts promotes osteoclast maturation and differentiation and causes progressive bone loss. (2) Inhibition of hypoxia-inducible factor-1α expression in osteoblasts impairs osteoclast activity, reduces bone resorption, and improves bone remodeling. Hypoxia-inducible factor-2α mediates the regulation between osteoblasts and osteoclasts to achieve bone remodeling. (3) The mechanism of hypoxia-inducible factor-3 in bone formation and bone remodeling has not been studied yet. (4) In osteoporosis, the decrease in osteoblast number, osteogenic function and angiogenic capacity inhibits the expression of hypoxia-inducible factor-α, causing a decrease in bone mass and bone density, which increases the risk of fracture. (5) In osteoarthritis, hypoxia-inducible factor-2α is significantly overexpressed, which stimulates chondrocyte apoptosis mediated by regulating the expression of inflammatory factors, matrix catabolic enzymes and other catabolic genes, and accelerates cartilage component. (6) In chondrosarcoma, neoangiogenesis is associated with hypoxia-inducible factor-1α overexpression, and hypoxia-inducible factor-1α can be used as a malignant marker associated with tumor neoangiogenesis in chondrosarcoma, and hypoxia-inducible factor-1 inhibition therapy can interfere with angiogenesis in chondrosarcoma. (7) Hypoxia-inducible factor plays an important role in regulating the angiogenesis process and the proliferation and activity of osteoblasts, osteoclasts, and chondrocytes in bone homeostasis imbalance diseases. The development of hypoxia-inducible factor-related activating or inhibiting drugs is very positive for repairing bone defects, accelerating fracture healing, improving bone joint inflammation and other bone homeostasis imbalance lesions.
Key words: hypoxia-inducible factor, HIF-1, HIF-2, bone formation, bone remodeling, bone homeostasis disorders, bone tumor, regulatory mechanism