›› 2009, Vol. 29 ›› Issue (8): 902-.

• Original article (Basic research) • Previous Articles     Next Articles

Expression and regulatory mechanism of hypoxia inducible factor-1alpha during fracture healing

LUO Tao, QI Jin, ZHOU Qi, WANG Jun, WANG Jin-shen, WEI Li, LIU Xiao-dong, DENG lian-fu   

  1. Shanghai Institute of Traumatology and Orthopedics, Shanghai Key Laboratory of Combination of Traditional Chinese and Western Medicine in Prevention and Therapy of Osteoarthropathy, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China
  • Online:2009-08-25 Published:2009-09-27
  • Supported by:

    National Natural Science Foundation of China, 30672145; Shanghai Science and Technology Committee Foundation, 06DZ22020, 07DZ22008

Abstract:

Objective To explore the expression and regulatory mechanism of hypoxia inducible factor-1α(HIF-1α)during fracture healing. Methods Mouse models of tibia fracture healing were established, and callus samples were collected 1, 3, 7, 14, 21 and 28 days after fracture. The development of callus and new bone formation were evaluated with roentgenology, Micro-CT and tetracycline double labeling method, and the expression of HIF-1α, vascular endothelial growth factor (VEGF), Runx2 and ALP in callus were detected with RT-PCR, Western blotting and immunohistochemistry. The relationship between HIF-1α and fracture healing was analysed. Results The expression of HIF-1α was detected in cells in the fracture sites as well as in evolved osteoblasts, chondrocytes and osteocytes in early callus under hypoxia. The highest expression rate of HIF-1α achieved on the 7th day after fracture, lasted for about 7 days, then decreased gradually, and returned to intact level on the 28th day after fracture. The expression tendency of VEGF resembled that of HIF-1α. Bone formation activity was more active in early callus, and the callus volume peaked on the 14th day after fracture and decreased gradually. The mineralization of callus mainly took place in the late healing period (14th to 28th day after fracture). Conclusion Cells involved in fracture healing are hypoxia-responsive cells, which express HIF-1α. HIF-1α can regulate cell state and function, and can promote angiogenesis so as to play a crucial role in fracture healing.

Key words: fracture healing, callus, hypoxia inducible factor-1α

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