›› 2009, Vol. 29 ›› Issue (11): 1305-.

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

Role of hypoxia inducible factor-1alpha and VHL in murine endochondral ossification

SHAO Jin, DENG Lian-fu, QI Jin, ZHOU Qi, WANG Jun, WEI Li, WANG Jin-shen, QIAN Nian-dong   

  1. Department of Orthopaedics, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China
  • Online:2009-11-25 Published:2009-11-24
  • Supported by:

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

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Abstract:

Objective To investigate the role of hypoxia inducible factor-1α (HIF-1α) and von Hippel-Lindau (VHL) in murine endochondral ossification. Methods The knockout of HIF-1α or VHL gene in murine osteoblasts was accomplished by conditional knockout technique at 4th, 8th and 12th week, and the differences between wild-type group and knock-out group in endochondral ossification were detected by HE staining, micro-CT scanning, trabecular bone area measurement, calcium content measurement, tetracycline fluorescence labeling, Real-time PCR and Western blotting. Results After knockout of HIF-1α gene in osteoblasts, the expression of vascular endothelial growth factor(VEGF) reduced, the rate of new bone formation stepped down, the content of calcium became less, and the trabecular bone volume decreased （P<0.05）. After knockout of VHL gene in osteoblasts, the expression of VEGF increased, the rate of new bone formation stepped up, the content of calcium became more, and the trabecular bone volume was promoted （P<0.001）. Conclusion During murine endochondral ossification, VHL/HIF-1α signal pathway promotes angiogenesis through the stimulation of VEGF expression，which subsequently accelerates osteogenesis.

Key words: hypoxia inducible factor-1α, von Hippel-Lindau, endochondral ossification